Type I Spontaneous Coronary Artery Dissection in a 33-Year-Old Male With Clinically Suspected Myopericarditis.

We report a 33-year-old male with uncontrolled type II diabetes, and tobacco and marijuana use who presented with chest pain after a night of binge drinking and vomiting. ECG changes were consistent with acute pericarditis. Troponin levels were found to be significantly elevated and rising. The patient was immediately treated with acetylsalicylic acid (ASA), morphine, nitroglycerin drip, and heparin drip. Echocardiogram showed preserved ejection fraction (EF) without effusion. Coronary angiography demonstrated a type I spontaneous coronary artery dissection (SCAD) of the mid-left anterior descending artery (LAD) without significant coronary artery disease. Diagnostic intravenous ultrasound (IVUS) confirmed a type I SCAD with penumbra and a minimal luminal area of 10 mm2 of the mid-LAD without significant luminal narrowing. Percutaneous intervention was performed with ultrasound-guided penumbra aspiration thrombectomy. Medical therapy was started with aspirin and ticagrelor, high-intensity statin, metoprolol tartrate, lisinopril, colchicine, and insulin. A biopsy or cardiac MRI was not performed due to the resolution of the patient's symptoms. We conclude that the development of a type I SCAD in this patient was multifactorial in nature, including clinically suspected acute myopericarditis, uncontrolled type II diabetes mellitus, and binge drinking associated with vomiting.

A Case Series of Spontaneous Pneumomediastinum With/Without Pneumothorax in COVID-19.

With the previous worldwide initial coronavirus disease 2019 (COVID-19) pandemic, a notable rise in spontaneous pneumomediastinum with/without pneumothorax (SPP) has been noted. Most cases were initially reported as complications secondary to barotrauma from mechanical ventilation (MV) with COVID-19. However, with the Delta strain, starting from December 2020, there have been multiple reports of SPP. The SPP is an uncommon complication outside use of assisted ventilation with either noninvasive positive pressure ventilation (NIPPV) or MV. COVID-19 has been linked to higher incidence of SPP without use of NIPPV or MV. We present a series of 5 cases with a polymerase chain reaction-confirmed COVID-19 diagnostic testing whose hospital course was complicated by SPP unrelated to the use of either NIPPV or MV.

Fascicular elastin within tendon contributes to the magnitude and modulus gradient of the elastic stress response across tendon type and species.

Elastin, the main component of elastic fibers, has been demonstrated to significantly influence tendon mechanics using both elastin degradation studies and elastinopathic mouse models. However, it remains unclear how prior results differ between species and functionally distinct tendons and, in particular, how results translate to human tendon. Differences in function between fascicular and interfascicular elastin are also yet to be fully elucidated. Therefore, this study evaluated the quantity, structure, and mechanical contribution of elastin in functionally distinct tendons across species. Tendons with an energy-storing function had slightly more elastin content than tendons with a positional function, and human tendon had at least twice the elastin content of other species. While distinctions in the organization of elastic fibers between fascicles and the interfascicular matrix were observed, differences in structural arrangement of the elastin network between species and tendon type were limited. Mechanical testing paired with enzyme-induced elastin degradation was used to evaluate the contribution of elastin to tendon mechanics. Across all tendons, elastin degradation affected the elastic stress response by decreasing stress values while increasing the modulus gradient of the stress-strain curve. Only the contributions of elastin to viscoelastic properties varied between tendon type and species, with human tendon and energy-storing tendon being more affected. These data suggest that fascicular elastic fibers contribute to the tensile mechanical response of tendon, likely by regulating collagen engagement under load. Results add to prior findings and provide evidence for a more mechanistic understanding of the role of elastic fibers in tendon. STATEMENT OF SIGNIFICANCE: Elastin has previously been shown to influence the mechanical properties of tendon, and degraded or abnormal elastin networks caused by aging or disease may contribute to pain and an increased risk of injury. However, prior work has not fully determined how elastin contributes differently to tendons with varying functional demands, as well as within distinct regions of tendon. This study determined the effects of elastin degradation on the tensile elastic and viscoelastic responses of tendons with varying functional demands, hierarchical structures, and elastin content. Moreover, volumetric imaging and protein quantification were used to thoroughly characterize the elastin network in each distinct tendon. The results presented herein can inform tendon-specific strategies to maintain or restore native properties in elastin-degraded tissue.

Growth of Highly-Ordered Metal Nanoparticle Arrays in the Dimpled Pores of an Anodic Aluminum Oxide Template.

A reliable, scalable, and inexpensive technology for the fabrication of ordered arrays of metal nanoparticles with large areal coverage on various substrates is presented. The nanoparticle arrays were formed on aluminum substrates using a two-step anodization process. By varying the anodization potential, the pore diameter, inter-pore spacing, and pore ordering in the anodic aluminum oxide (AAO) template were tuned. Following a chemical etch, the height of the pores in the AAO membrane were reduced to create a dimpled membrane surface. Periodic arrays of metal nanoparticles were subsequently created by evaporating metal on to the dimpled surface, allowing for individual nanoparticles to form within the dimples by a solid state de-wetting process induced by annealing. The ordered nanoparticle array could then be transferred to a substrate of choice using a polymer lift-off method. Following optimization of the experimental parameters, it was possible to obtain cm2 coverage of metal nanoparticles, like gold and indium, on silicon, quartz and sapphire substrates, with average sizes in the range of 50-90 nm. The de-wetting process was investigated for a specific geometry of the dimpled surface and the results explained for two different film thicknesses. Using a simple model, the experimental results were interpreted and supported by numerical estimations.

Mycoplasma pneumoniae COVID-19 Delta Variant Co-Infection Mimicking COVID-19 ARDS.

The Delta variant of COVID-19 has been associated with severe disease causing a surge in the second half of 2021. Atypical pathogens can be present in those in particular with severe ARDS and can contribute to excess morbidity and mortality. We must maintain a high level of suspicion for these pathogens as this can present an opportunity to dramatically improve the prognosis of a patient with COVID-19 ARDS. However, lend caution to Mycoplasma IgM serology as this can be a false-positive. If suspicion remains high for Mycoplasma pneumoniae infection, sputum polymerase chain reaction (PCR) for M pneumoniae is the gold standard for diagnosis. We present the case of a 42-year-old female with COVID-19 Delta variant presumed ARDS who had co-infection with M pneumoniae confirmed by endotracheal sputum aspirate PCR with rapidly improving oxygenation and extubation within 4 days of effective antibiotic therapy.

Pleiotropic Effects of Simvastatin and Losartan in Preclinical Models of Post-Traumatic Elbow Contracture.

Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: an in vivo elbow-specific rat injury model and an in vitro collagen gel contraction assay. The in vivo elbow rat (n = 3-10/group) injury model evaluated the effects of orally administered SV and LS at two dosing strategies [i.e., low dose/high frequency/short duration (D1) vs. high dose/low frequency/long duration (D2)] on post-mortem elbow range of motion (via biomechanical testing) as well as capsule fibrosis and cartilage damage (via histopathology). The in vitro gel contraction assay coupled with live/dead staining (n = 3-19/group) evaluated the effects of SV and LS at various concentrations (i.e., 1, 10, 100 µM) and durations (i.e., continuous, short, or delayed) on the contractibility and viability of fibroblasts/myofibroblasts [i.e., NIH3T3 fibroblasts with endogenous transforming growth factor-beta 1 (TGFß1)]. In vivo, no drug strategy prevented elbow contracture biomechanically. Histologically, only SV-D2 modestly reduced capsule fibrosis but maintained elevated cellularity and tissue hypertrophy, and both SV strategies lessened cartilage damage. SV modest benefits were localized to the anterior region, not the posterior, of the joint. Neither LS strategy had meaningful benefits in capsule nor cartilage. In vitro, irrespective of the presence of TGFß1, SV (≥10 µM) prevented gel contraction partly by decreasing cell viability (100 µM). In contrast, LS did not prevent gel contraction or affect cell viability. This study demonstrates that SV, but not LS, might be suitable prophylactic drug therapy in two preclinical models of elbow PTJC. Results provide initial insight to guide future preclinical studies aimed at preventing or mitigating elbow PTJC.

Design of a portable device to store and disinfect masks of SARS-CoV-2 virus using Peltier modules.

The current pandemic has disrupted our routines and masks which were nowhere to be seen have become an essential part of our day-to-day life. The means to carry a mask without contaminating it and also disinfecting them is a challenge in the current scenario and should be so for some time to come. The portable device proposed through this study for storing and disinfecting masks embeds mechanical and electronic design. The device consists of a box that can house six masks, is compact, easy to carry and can disinfect masks. The main purpose is to heat the mask placed inside the box above the temperature of 65 °C for a duration greater than three minutes, so that bacteria and viruses such as SARS-CoV-2 can be eliminated and the mask can be kept safe, disinfected and reused. This in turn helps to reduce the waste caused by disposing masks and enables portability of masks in a safe and hygienic manner. The box comprises of two Peltier modules controlled by the ATtiny85 microcontroller, a metal plate that is in contact with the Peltier modules, two Li-Po batteries as power supply and a switch to turn on the device. The box can be recharged easily using the micro-USB port.

Cardiac risk stratification in cancer patients: A longitudinal patient-patient network analysis.

BACKGROUND: Cardiovascular disease is a leading cause of death in general population and the second leading cause of mortality and morbidity in cancer survivors after recurrent malignancy in the United States. The growing awareness of cancer therapy-related cardiac dysfunction (CTRCD) has led to an emerging field of cardio-oncology; yet, there is limited knowledge on how to predict which patients will experience adverse cardiac outcomes. We aimed to perform unbiased cardiac risk stratification for cancer patients using our large-scale, institutional electronic medical records. METHODS AND FINDINGS: We built a large longitudinal (up to 22 years' follow-up from March 1997 to January 2019) cardio-oncology cohort having 4,632 cancer patients in Cleveland Clinic with 5 diagnosed cardiac outcomes: atrial fibrillation, coronary artery disease, heart failure, myocardial infarction, and stroke. The entire population includes 84% white Americans and 11% black Americans, and 59% females versus 41% males, with median age of 63 (interquartile range [IQR]: 54 to 71) years old. We utilized a topology-based K-means clustering approach for unbiased patient-patient network analyses of data from general demographics, echocardiogram (over 25,000), lab testing, and cardiac factors (cardiac). We performed hazard ratio (HR) and Kaplan-Meier analyses to identify clinically actionable variables. All confounding factors were adjusted by Cox regression models. We performed random-split and time-split training-test validation for our model. We identified 4 clinically relevant subgroups that are significantly correlated with incidence of cardiac outcomes and mortality. Among the 4 subgroups, subgroup I (n = 625) has the highest risk of de novo CTRCD (28%) with an HR of 3.05 (95% confidence interval (CI) 2.51 to 3.72). Patients in subgroup IV (n = 1,250) had the worst survival probability (HR 4.32, 95% CI 3.82 to 4.88). From longitudinal patient-patient network analyses, the patients in subgroup I had a higher percentage of de novo CTRCD and a worse mortality within 5 years after the initiation of cancer therapies compared to long-time exposure (6 to 20 years). Using clinical variable network analyses, we identified that serum levels of NT-proB-type Natriuretic Peptide (NT-proBNP) and Troponin T are significantly correlated with patient's mortality (NT-proBNP > 900 pg/mL versus NT-proBNP = 0 to 125 pg/mL, HR = 2.95, 95% CI 2.28 to 3.82, p < 0.001; Troponin T > 0.05 µg/L versus Troponin T ≤ 0.01 µg/L, HR = 2.08, 95% CI 1.83 to 2.34, p < 0.001). Study limitations include lack of independent cardio-oncology cohorts from different healthcare systems to evaluate the generalizability of the models. Meanwhile, the confounding factors, such as multiple medication usages, may influence the findings. CONCLUSIONS: In this study, we demonstrated that the patient-patient network clustering methodology is clinically intuitive, and it allows more rapid identification of cancer survivors that are at greater risk of cardiac dysfunction. We believed that this study holds great promise for identifying novel cardiac risk subgroups and clinically actionable variables for the development of precision cardio-oncology.

Cystic fibrosis foundation consensus statements for the care of cystic fibrosis lung transplant recipients.

Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed by the committee members based on literature review, committee experience and iterative revisions, and in response to public comment. The committee formulated 32 recommendation statements in the topics related to infectious disease, endocrine, gastroenterology, pharmacology, mental health and family planning. Broadly, the committee recommends close coordination of care between the lung transplant team, the cystic fibrosis care center, and specialists in other disciplines with experience in the care of CF and lung transplant recipients. These consensus statements will help lung transplant providers care for CFLTRs in order to improve post-transplant outcomes in this population.

Luminal Gastrointestinal Manifestations of Cystic Fibrosis.

PURPOSE OF REVIEW: People with cystic fibrosis (CF) are living longer. General age-related and CF-specific gastrointestinal symptoms are increasingly recognized. In this article, we review the latest data on luminal gastrointestinal manifestations in CF. RECENT FINDINGS: People with CF have increased incidence of gastroesophageal reflux disease symptoms and often prescribed proton-pump inhibitors (PPI). PPI use may increase risk of pulmonary exacerbations. Evidence to support gastric fundoplication to improve pulmonary outcomes is limited. Features of intestinal dysmotility are common. There are distinct differences in the gut microbiome in the CF population which may have clinical implications. CF is a possible hereditary digestive cancer syndrome, particularly in regard to colorectal cancer (CRC) with earlier incidence of CRC and advanced colonic neoplasia. Early screening colonoscopy is warranted in the CF population. Gastrointestinal manifestations in CF are prevalent across all digestive organs. More study on the effect of interventions for symptomatic treatment and cancer screening is needed.

May-Thurner Compressive Syndrome Unmasked by Rapid Weight Loss.

Description May-Thurner Syndrome (MTS) is an anatomical syndrome characterized by a predisposition to clot formation when there is compression of the left iliac vein by the right iliac artery. In this case, we discuss an atypical presentation of MTS in a young male after rapid weight loss. The patient was admitted for an unprovoked massive proximal deep vein thrombosis (DVT) after a two-hundred-pound weight loss during the preceding six-month period. Treatment involved mechanical thrombectomy by interventional radiology, initiation of apixaban and recommended follow up with vascular surgery for angioplasty instead of immediate stent placement.

Normal Ranges of Thiopurine Methyltransferase Activity Do Not Affect Thioguanine Nucleotide Concentrations With Azathioprine Therapy in Inflammatory Bowel Disease.

Background: Thiopurine methyltransferase (TPMT) activity influences azathioprine conversion into active metabolite 6-thioguanine nucleotide (6-TGN). Low TPMT activity correlates with high 6-TGN and risk for myelosuppression. Conversely, normal-to-high TPMT activity may be associated with low 6-TGN and drug resistance, the so-called hypermetabolizers. Our aim was to identify the effect of normal-to-high TPMT activity on 6-TGN concentrations in an inflammatory bowel disease population. Methods: A retrospective chart review of patients aged ≥18 with inflammatory bowel disease, on azathioprine, with documented TPMT activity and 6-TGN concentration was performed. Correlations were evaluated via the Spearman rho correlation coefficient. Linear regression was used to determine the effect of TPMT activity on 6-TGN accounting for confounders. Relationships between TPMT activity, drug dose, and 6-TGN levels were defined via average causal mediation effects. Results: One hundred patients were included. No correlation was observed between TPMT activity, azathioprine dosing, and metabolite concentrations. Overall, 39% of the cohort had a therapeutic 6-TGN level of >230 pmol/8 × 108 red blood cells (RBCs). No patient under 1 mg/kg achieved a therapeutic 6-TGN level, whereas 42% of patients taking 2.5 mg/kg did. The median 6-TGN concentration was higher for those in remission (254 pmol/8 × 108 RBCs, interquartile range: 174, 309) versus those not in remission (177 pmol/8 × 108 RBCs, interquartile range: 94.3, 287.8), though not significantly (P = 0.08). Smoking was the only clinical factor associated with 6-TGN level. On multivariate linear regression, only age, azathioprine dose, and obese body mass index were predictive of metabolite concentration. Conclusions: Variations within the normal range of TPMT activity do not affect 6-TGN concentration.

Case report of synchronous post-lung transplant colon cancers in the era of colorectal cancer screening recommendations in cystic fibrosis: screening "too early" before it's too late.

BACKGROUND: The increasing life expectancy of individuals with Cystic Fibrosis (CF) is likely to be associated with new age-related challenges, colorectal cancer (CRC) most notably; recent consensus recommendations for CRC screening published in 2018 represent an important early step in addressing the emerging awareness of CF as a gastrointestinal cancer syndrome. These recommendations, however, need to be further refined based on more systematic data. We discuss an illustrative first-ever case of synchronous CRC arising in a post-lung transplant individual with CF within the recommended surveillance interval after a well-documented prior normal colonoscopy. CASE PRESENTATION: A 51-year-old female individual with homozygous F508del CF, presents to clinic with abdominal discomfort and intermittent blood in stools. She had previously undergone bilateral lung transplantation 18 years earlier, as well as two kidney transplants related to immunosuppression-related nephrotoxicity. A diagnostic colonoscopy was performed which revealed the presence of two separate synchronous colon cancers in the cecum and transverse colon; she had undergone a colonoscopy three years prior to this exam which was structurally normal. Endoscopic quality indicators, including a good quality bowel preparation, colonoscopic withdrawal time > 12 min, and quarterly Adenoma Detection Rate (ADR) ranging from 50 to 70% for both male and female patients for the endoscopist from both colonoscopic exams, as well as secondary retrospective comparative review of the pertinent case images, diminish the risk for a "missed" cancer or advanced lesion on the index exam. These cancers did not demonstrate any immunohistochemical features suggestive of Lynch Syndrome, though the rapid progression to cancer within the surveillance interval (possibly non-polypoid in nature) is similar. This cancer presentation within the newly-established recommended colon cancer screening interval warrants concern. CONCLUSIONS: This case prompts serious discussion regarding the length of surveillance intervals in the post-transplant CF population (a population at 20-30 times greater risk for CRC compared to the general non-CF population), as well as the importance of documenting endoscopic quality benchmarks, particularly if a narrative of interval CRC development continues to develop with further prospective monitoring and multi-center experience.

Cystic Fibrosis & disorders of the large intestine: DIOS, constipation, and colorectal cancer.

Since 1966 when the Cystic Fibrosis Foundation Patient Registry (CFFPR) was founded, clinicians have witnessed significant advances in both the quality and quantity of life for patients living with Cystic Fibrosis (CF). As patients with CF live longer and fuller lives, increasing encumbrances from gastrointestinal manifestations of CF will be observed. This article serves to discuss "below the diaphragm" concerns involving the large intestine (Distal Intestinal Obstruction Syndrome, Constipation, and Colorectal Cancer). Avenues for development and implementation of clinical care protocols, particularly regarding proactive management of known associated conditions and cancer screening, will continue to be refined in the coming years. It falls to the multidisciplinary CF care team to be actively engaged in addressing these concerns effectively as priority shifts from relative acuity (typically related to early nutrition and lung function) to the travails of longevity as the CF population continues to age.

Fecal Occult Blood Testing in Hospitalized Patients with Upper Gastrointestinal Bleeding.

A 47-year-old man with a history of alcohol abuse, cirrhosis, and grade II esophageal varices is admitted for treatment of alcohol withdrawal. He reports having some dark-colored stools a week prior to admission, but his stools since then have been normal in color. A repeat hemoglobin is stable, but a fecal occult blood test is positive. What should be done next?

The synthesis and biological activity of novel anthracenone-pyranones and anthracenone-furans.

An efficient and divergent methodology for the synthesis of new anthracenone-pyranones and anthracenone-furans is described. Key reactions discussed in these syntheses include an aldehyde promoted annulation with a ß-keto-sulfoxide, a domino alkyne insertion/carbonylation/Nu-acylation and a DMEDA promoted Castro-Stephens reaction. We also report the in vitro growth inhibition of these compounds in a range of human cancer cells. The natural product BE-26554A displayed good cell growth activity on BE2-C neuroblastoma and SMA glioblastoma cell lines at 0.17 and 0.16µM (GI50), respectively. Of note, were a CF3 functionalised anthracenone 4-pyranone (chromone) derivative 22, and an anthracenone-furan derivative 54 which displayed 0.20µM and 0.38µM growth inhibition, respectively, in the BE2-C neuroblastoma cell line.

Infectious Disease Consultation for Staphylococcus aureus Bacteremia Improves Patient Management and Outcomes.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is a common, severe infectious disease with accepted standards of care. METHODS: A retrospective cohort study of all 233 SAB cases at the Minneapolis Veterans Affairs Medical Center (MVAMC) between October 2004 and February 2008 was performed to measure the impact of Infectious Disease (ID) consultation on conformance to standards and patient outcomes. Outcomes were classified as survived without relapse, relapsed, or died without relapse. ID involvement was classified as consultation, curbside, or no involvement. RESULTS: ID involvement occurred in 179/233 cases (77%). Management conformed to accepted standards in 162/197 cases (82%) evaluable for conformance. ID involvement was associated with increased conformance in univariable analysis and multivariable analysis adjusted for propensity for ID consultation (OR 5.9, 95% CI 2.5 - 13.8). Relapse occurred in 14/156 cases (9%) in which therapy conformed to standards compared with 8/35 cases (23%) in which therapy did not conform to standards (p=0.045). Relapse was more common in older patients (OR 1.05, CI 1.01-1.09) and in cases without ID involvement (OR 3.02, CI 1.003-9.1). Death was associated with greater Charlson Index scores (OR 1.89, CI 1.4-2.5). Of 111 cases with definitely or possibly infected devices, relapse occurred in 9/92 cases (9.8%) in which the device was wholly or partially removed compared with 6/19 cases (32%) in which the device was left in place (p=0.02). CONCLUSIONS: ID involvement in SAB cases was associated with increased adherence to accepted standards and fewer relapses. ID consultation should be performed for all SAB cases.