Anhydrous Nucleic Acid Nanoparticles for Storage and Handling at Broad Range of Temperatures.

Recent advances in nanotechnology now allow for the methodical implementation of therapeutic nucleic acids (TNAs) into modular nucleic acid nanoparticles (NANPs) with tunable physicochemical properties which can match the desired biological effects, provide uniformity, and regulate the delivery of multiple TNAs for combinatorial therapy. Despite the potential of novel NANPs, the maintenance of their structural integrity during storage and shipping remains a vital issue that impedes their broader applications. Cold chain storage is required to maintain the potency of NANPs in the liquid phase, which greatly increases transportation costs. To promote long-term storage and retention of biological activities at higher temperatures (e.g., +50 °C), a panel of representative NANPs is first exposed to three different drying mechanisms-vacuum concentration (SpeedVac), lyophilization (Lyo), and light-assisted drying (LAD)-and then rehydrated and analyzed. While SpeedVac primarily operates using heat, Lyo avoids temperature increases by taking advantage of pressure reduction and LAD involves a near-infrared laser for uniform drying in the presence of trehalose. This work compares and defines refinements crucial in formulating an optimal strategy for producing stable, fully functional NANPs and presents a forward advancement in their development for clinical applications.

Endoscopic-Assisted Intraoral Approach for Osteosynthesis of Mandibular Subcondylar Fractures.

INTRODUCTION: The aim of this study is to follow-up and evaluate the treatment result of mandibular subcondylar (MSC) fractures by osteosynthesis via endoscopy-assisted intraoral approach. MATERIALS AND METHODS: This is a prospective study, in which 47 patients with 51 sites of MSC fractures treated osteosynthesis via endoscopic-assisted intraoral approach at the Department of Maxillofacial Surgery, National Hospital of Odonto-Stomatology HoChiMinh City-Vietnam were followed-up and evaluated clinically and radiographically up to 6 months postoperative. RESULTS: Before surgery, all of the patients were malocclusion, 15% of patients were isolated MSC fractures, the rate of concomitant midface fractures were 30%, 92.2% of fracture sites with moderate displacement, 7.8% of fracture sites with severe displacement, 5.9% of fracture sites with dislocation. After surgery, all of the patients had preinjured centric occlusion; no patient had facial paralysis; 6% of patients had surgical site infection within 1 week; pain frequency were 56.9% at 1 month, 35.3% at 2 months, 7.8% at 3 months, and 2.0% at 6 months with Visual Analog Scale (VAS) means of pain were 1.74±1.85 at 1 month, 0.55±1.12 at 2 months, 0.08±0.27 at 3 months and 0.02±0.14 at 6 months; 90% of fracture sites had precise anatomy at 1 week and 96% at 6 months; 96% fracture sites had no displacement the of correlation between condyle and articular fossa at 1 week and 98% at 6 months; 1 fracture site had screw loosening at 2 months; 88% fracture sites had stage-4 radiographic bone healing at 6 months. CONCLUSION: Endoscopic-assisted intraoral approach for osteosynthesis of MSC fractures have provided the esthetic and functional success and good bone healing.

Considerations for the use of Cre recombinase for conditional gene deletion in the mouse lens.

BACKGROUND: Despite a number of different transgenes that can mediate DNA deletion in the developing lens, each has unique features that can make a given transgenic line more or less appropriate for particular studies. The purpose of this work encompasses both a review of transgenes that lead to the expression of Cre recombinase in the lens and a comparative analysis of currently available transgenic lines with a particular emphasis on the Le-Cre and P0-3.9GFPCre lines that can mediate DNA deletion in the lens placode. Although both of these transgenes are driven by elements of the Pax6 P0 promoter, the Le-Cre transgene consistently leads to ocular abnormalities in homozygous state and can lead to ocular defects on some genetic backgrounds when hemizygous. RESULT: Although both P0-3.9GFPCre and Le-Cre hemizygous transgenic mice undergo normal eye development on an FVB/N genetic background, Le-Cre homozygotes uniquely exhibit microphthalmia. Examination of the expression patterns of these two transgenes revealed similar expression in the developing eye and pancreas. However, lineage tracing revealed widespread non-ocular CRE reporter gene expression in the P0-3.9GFPCre transgenic mice that results from stochastic CRE expression in the P0-3.9GFPCre embryos prior to lens placode formation. Postnatal hemizygous Le-Cre transgenic lenses express higher levels of CRE transcript and protein than the hemizygous lenses of P0-3.9GFPCre mice. Transcriptome analysis revealed that Le-Cre hemizygous lenses deregulated the expression of 15 murine genes, several of which are associated with apoptosis. In contrast, P0-3.9GFPCre hemizygous lenses only deregulated two murine genes. No known PAX6-responsive genes or genes directly associated with lens differentiation were deregulated in the hemizygous Le-Cre lenses. CONCLUSIONS: Although P0-3.9GFPCre transgenic mice appear free from ocular abnormalities, extensive non-ocular CRE expression represents a potential problem for conditional gene deletion studies using this transgene. The higher level of CRE expression in Le-Cre lenses versus P0-3.9GFPCre lenses may explain abnormal lens development in homozygous Le-Cre mice. Given the lack of deregulation of PAX6-responsive transcripts, we suggest that abnormal eye development in Le-Cre transgenic mice stems from CRE toxicity. Our studies reinforce the requirement for appropriate CRE-only expressing controls when using CRE as a driver of conditional gene targeting strategies.

Post-TTM Rebound Pyrexia after Ischemia-Reperfusion Injury Results in Sterile Inflammation and Apoptosis in Cardiomyocytes.

INTRODUCTION: Fever is frequently observed after acute ischemic events and is associated with poor outcome and higher mortality. Targeted temperature management (TTM) is recommended for neuroprotection in comatose cardiac arrest survivors, but pyrexia after rewarming is proven to be detrimental in clinical trials. However, the cellular mechanisms and kinetics of post-TTM rebound pyrexia remain to be elucidated. Therefore, we investigated the effects of cooling and post-TTM pyrexia on the inflammatory response and apoptosis in a cardiomyocyte ischemia-reperfusion (IR) injury model. METHODS: HL-1 cardiomyocytes were divided into the following groups to investigate the effect of oxygen-glucose deprivation/reperfusion (OGD/R), hypothermia (33.5°C), and pyrexia (40°C): normoxia controls maintained at 37°C and warmed to 40°C, OGD/R groups maintained at 37°C and cooled to 33.5°C for 24 h with rewarming to 37°C, and OGD/R pyrexia groups further warmed from 37 to 40°C. Caspase-3 and RBM3 were assessed by Western blot and TNF-α, IL-6, IL-1ß, SOCS3, iNOS, and RBM3 transcriptions by RT-qPCR. RESULTS: OGD-induced oxidative stress (iNOS) in cardiomyocytes was attenuated post-TTM by cooling. Cytokine transcriptions were suppressed by OGD, while reperfusion induced significant TNF-α transcription that was exacerbated by cooling. Significant inductions of TNF-α, IL-6, IL-1ß, and SOCS3 were observed in noncooled, but not in cooled and rewarmed, OGD/R-injured cardiomyocytes. Further warming to pyrexia induced a sterile inflammatory response in OGD/R-injured groups that was attenuated by previous cooling, but no inflammation was observed in pyrexic normoxia groups. Moreover, cytoprotective RBM3 expression was induced by cooling but suppressed by pyrexia, correlating with apoptotic caspase-3 activation. CONCLUSION: Our findings show that maintaining a period of post-TTM "therapeutic normothermia" is effective in preventing secondary apoptosis-driven myocardial cell death, thus minimizing the infarct area and further release of mediators of the innate sterile inflammatory response after acute IR injury.

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration.

Residual calcified material volume of ß-tricalcium phosphate with platelet-rich fibrin in unilateral alveolar bone graft.

BACKGROUND: This study aimed to evaluate the effectiveness of ß-tricalcium phosphate (ß-TCP) and platelet-rich fibrin (PRF) in unilateral alveolar bone graft, involving the percentage of residual calcified material and the average labiopalatal thickness of the grafts on cone beam computed tomography at 6 months after surgery, comparing two age groups 12 years and under and over 12 years old. RESULTS: The mean preoperative defect volume was 0.93 ± 0.20 cm3, with no significant difference between the two groups (p = 0.652). In the postoperative period, we did not record any abnormal bleeding and no infection was observed. Six months after surgery, the mean percentage of residual calcified material was 63.53 ± 16.48% with a significantly higher difference in the age group 12 and under (p < 0.001), and the mean average labiopalatal thickness of the grafted bone was 5.72 ± 1.09 mm with a significantly higher difference in the age group 12 and under (p = 0.011). CONCLUSION: Using ß-TCP and PRF in alveolar bone graft surgery has acceptable effectiveness clinically and on CBCT images, with significantly higher differences of the percentage of residual calcified material and the average labiopalatal thickness of the grafted bone in the group 12 years old and younger than in the older group.

Improvement of the Impacted Level of Lower Third Molars After Orthodontic Treatment.

OBJECTIVES: The early or delayed surgical removal of an asymptomatic lower third molar (M3) in orthodontic patients remains controversial. This study aimed to determine the changes in the impacted level of M3 such as angulation, vertical position, and eruption space, after orthodontic treatment in 3 groups, namely non-extraction (NE), first premolar (P1) extraction, and second premolar (P2) extraction. METHODS: Relevant angles and distances related to 334 M3s from 180 orthodontic patients were assessed pre- and posttreatment. Angle between lower second molar (M2) and M3 (M3-M2) was used for evaluating M3 angulation. For M3 vertical position, distances from occlusal plane to the highest cuspid (Cus-OP) and fissure (Fis-OP) of M3 were used. Distances from the distal surface of M2 to anterior border (J-DM2) and centre (Xi-DM2) of the ramus were used for assessing M3 eruption space. Pre- and posttreatment values of the angle and distance in each group were compared using a paired-sample t test. Measurements of the 3 groups were compared using analysis of variance. Hence, multiple linear regression (MLR) analysis was used to determine significant factors that impacted changes in M3s' related measurements. Independent factors used for MLR analysis included sex, treatment starting age, pretreatment respective angle/distance, and premolar extraction (NE/P1/P2). RESULTS: M3 angulation, vertical position, and eruption space at posttreatment were significantly different from those at pretreatment in all 3 groups. MLR analysis showed that P2 extraction significantly improved M3 vertical position (P < .05) and eruption space (P < .001). P1 extraction significantly decreased Cus-OP (P = .014) and eruption space (P < .001). Treatment starting age was significant factor that affected Cus-OP (P = .001) and M3 eruption space (P < .001). CONCLUSIONS: After orthodontic treatment, M3 angulation, vertical position, and eruption space changed in favour of the impacted level. These changes in the 3 groups were clearer in order: NE, P1, and P2, respectively.

Assessing surface water pollution in Hanoi, Vietnam, using remote sensing and machine learning algorithms.

Rapid urbanization led to significant land-use changes and posed threats to surface water bodies worldwide, especially in the Global South. Hanoi, the capital city of Vietnam, has been facing chronic surface water pollution for more than a decade. Developing a methodology to better track and analyze pollutants using available technologies to manage the problem has been imperative. Advancement of machine learning and earth observation systems offers opportunities for tracking water quality indicators, especially the increasing pollutants in the surface water bodies. This study introduces machine learning with the cubist model (ML-CB), which combines optical and RADAR data, and a machine learning algorithm to estimate surface water pollutants including total suspended sediments (TSS), chemical oxygen demand (COD), and biological oxygen demand (BOD). The model was trained using optical (Sentinel-2A and Sentinel-1A) and RADAR satellite images. Results were compared with field survey data using regression models. Results show that the predictive estimates of pollutants based on ML-CB provide significant results. The study offers an alternative water quality monitoring method for managers and urban planners, which could be instrumental in protecting and sustaining the use of surface water resources in Hanoi and other cities of the Global South.

Kinetics study of reactions of α-pinene and ß-pinene with hydroxyl radical at 1-8 Torr and 240-340 K using the relative rate/discharge flow/mass spectrometry method.

The kinetics of reactions of α-pinene and ß-pinene with hydroxyl radicals (OH) has been investigated at 1-8 Torr and 240-340 K using the relative rate/discharge flow/mass spectrometry (RR/DF/MS) technique. Our kinetic results indicate that at 298 K the rate constant of the reactions of α-pinene and ß-pinene with hydroxyl radicals has little pressure dependence over the 1-8 Torr pressure range, suggesting that the high pressure limit of these reactions has been reached at 1 Torr. The rate constant of these reactions was found to negatively depend on the temperature at 240-340 K, which is consistent with previous investigations using different techniques. The Arrhenius equation for α-pinene and ß-pinene with hydroxyl radical was determined to be k(α-pinene) = (1.21 ± 0.20) × 10(-11)exp[(441 ± 46)/T] cm(3) molecule(-1) s(-1) and k(ß-pinene) = (1.65 ± 0.10) × 10(-11)exp[(470 ± 17)/T] cm(3) molecule(-1) s(-1), respectively. Using the rate constant determined at 277 K in this work and the average global hydroxyl radical concentration, the atmospheric lifetime of α-pinene and ß-pinene was estimated to be 5.8 and 3.8 h, respectively.

The Application of Light-Assisted Drying to the Thermal Stabilization of Nucleic Acid Nanoparticles.

Background: Cold-chain storage can be challenging and expensive for the transportation and storage of biologics, especially in low-resource settings. Nucleic acid nanoparticles (NANPs) are an example of new biological products that require refrigerated storage. Light-assisted drying (LAD) is a new processing technique to prepare biologics for anhydrous storage in a trehalose amorphous solid matrix at ambient temperatures. In this study, LAD was used to thermally stabilize four types of NANPs with differing structures and melting temperatures. Methods: Small volume samples (10 µL) containing NANPs were irradiated with a 1064 nm laser to speed the evaporation of water and create an amorphous trehalose preservation matrix. Samples were then stored for 1 month at 4°C or 20°C. A FLIR C655 mid-IR camera was used to record the temperature of samples during processing. The trehalose matrix was characterized using polarized light imaging (PLI) to determine if crystallization occurred during processing or storage. Damage to LAD-processed NANPs was assessed after processing and storage using gel electrophoresis. Results: Based on the end moisture content (EMC) as a function time and the thermal histories of samples, a LAD processing time of 30 min is sufficient to achieve low EMCs for the 10 µL samples used in this study. PLI demonstrates that the trehalose matrix was resistant to crystallization during processing and after storage at 4°C and at room temperature. The native-polyacrylamide gel electrophoresis results for DNA cubes, RNA cubes, and RNA rings indicate that the main structures of these NANPs were not damaged significantly after LAD processing and being stored at 4°C or at room temperature for 1 month. Conclusions: These preliminary studies indicate that LAD processing can stabilize NANPs for dry-state storage at room temperature, providing an alternative to refrigerated storage for these nanomedicine products.

Analysis of Worsening Heart Failure Events in an Integrated Health Care System.

BACKGROUND: There is growing interest to disentangle worsening heart failure (WHF) from location of care and move away from hospitalization as a surrogate for acuity. OBJECTIVES: The purpose of this study was to describe the incidence of WHF events across the care continuum from ambulatory encounters to hospitalizations. METHODS: We studied calendar year cohorts of adults with diagnosed heart failure (HF) from 2010-2019 within a large, integrated health care delivery system. Electronic health record (EHR) data were accessed for outpatient encounters, emergency department (ED) visits/observation stays, and hospitalizations. WHF was defined as ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Symptoms and signs were ascertained using natural language processing. RESULTS: We identified 103,138 eligible individuals with mean age 73.6 ± 13.7 years, 47.5% women, and mean left ventricular ejection fraction of 51.4% ± 13.7%. There were 1,136,750 unique encounters including 743,039 (65.4%) outpatient encounters, 224,670 (19.8%) ED visits/observation stays, and 169,041 (14.9%) hospitalizations. A total of 126,008 WHF episodes were identified, including 34,758 (27.6%) outpatient encounters, 28,301 (22.5%) ED visits/observation stays, and 62,949 (50.0%) hospitalizations. The annual incidence (events per 100 person-years) of WHF increased from 25 to 33 during the study period primarily caused by outpatient encounters (7 to 10) and ED visits/observation stays (4 to 7). The 30-day rate of hospitalizations for WHF ranged from 8.2% for outpatient encounters to 12.4% for hospitalizations. CONCLUSIONS: ED visits/observation stays and outpatient encounters account for approximately one-half of WHF events, are driving the underlying growth in HF morbidity, and portend a poor short-term prognosis.

Design and Characterization of Biomimetic Kerateine Aerogel-Electrospun Polycaprolactone Scaffolds for Retinal Cell Culture.

Age-related macular degeneration (AMD) is a retinal disease that affects 196 million people and causes nearly 9% of blindness worldwide. While several pharmacological approaches slow the effects of AMD, in our opinion, cell-based strategies offer the most likely path to a cure. We describe the design and initial characterization of a kerateine (obtained by reductive extraction from keratin proteins) aerogel-electrospun polycaprolactone fiber scaffold system. The scaffolds mimic key features of the choroid and the Bruch's membrane, which is the basement membrane to which the cells of the retinal pigment epithelium (RPE) attach. The scaffolds had elastic moduli of 2-7.2 MPa, a similar range as native choroid and Bruch's membrane. ARPE-19 cells attached to the polycaprolactone fibers, remained viable for one week, and proliferated to form a monolayer reminiscent of that needed for retinal repair. These constructs could serve as a model system for testing cell and/or drug treatment strategies or directing ex vivo retinal tissue formation in the treatment of AMD.

A Natural Language Processing-Based Approach for Identifying Hospitalizations for Worsening Heart Failure Within an Integrated Health Care Delivery System.

Importance: The current understanding of epidemiological mechanisms and temporal trends in hospitalizations for worsening heart failure (WHF) is based on claims and national reporting databases. However, these data sources are inherently limited by the accuracy and completeness of diagnostic coding and/or voluntary reporting. Objective: To assess the overall burden of and temporal trends in the rate of hospitalizations for WHF. Design, Setting, and Participants: This cohort study, performed from January 1, 2010, to December 31, 2019, used electronic health record (EHR) data from a large integrated health care delivery system. Exposures: Calendar year trends. Main Outcomes and Measures: Hospitalizations for WHF (ie, excluding observation stays) were defined as 1 symptom or more, 2 objective findings or more including 1 sign or more, and 2 doses or more of intravenous loop diuretics and/or new hemodialysis or continuous kidney replacement therapy. Symptoms and signs were identified using natural language processing (NLP) algorithms applied to EHR data. Results: The study population was composed of 118 002 eligible patients experiencing 287 992 unique hospitalizations (mean [SD] age, 75.6 [13.1] years; 147 203 [51.1%] male; 1655 [0.6%] American Indian or Alaska Native, 28 451 [9.9%] Asian or Pacific Islander, 34 903 [12.1%] Black, 23 452 [8.1%] multiracial, 175 840 [61.1%] White, and 23 691 [8.2%] unknown), including 65 357 with a principal discharge diagnosis and 222 635 with a secondary discharge diagnosis of HF. The study population included 59 868 patients (20.8%) with HF with a reduced ejection fraction (HFrEF) (<40%), 33 361 (11.6%) with HF with a midrange EF (HFmrEF) (40%-49%), 142 347 (49.4%) with HF with a preserved EF (HFpEF) (≥50%), and 52 416 (18.2%) with unknown EF. A total of 58 042 admissions (88.8%) with a primary discharge diagnosis of HF and 62 764 admissions (28.2%) with a secondary discharge diagnosis of HF met the prespecified diagnostic criteria for WHF. Overall, hospitalizations for WHF identified on NLP-based algorithms increased from 5.2 to 7.6 per 100 hospitalizations per year during the study period. Subgroup analyses found an increase in hospitalizations for WHF based on NLP from 1.5 to 1.9 per 100 hospitalizations for HFrEF, from 0.6 to 1.0 per 100 hospitalizations for HFmrEF, and from 2.6 to 3.9 per 100 hospitalizations for HFpEF. Conclusions and Relevance: The findings of this cohort study suggest that the burden of hospitalizations for WHF may be more than double that previously estimated using only principal discharge diagnosis. There has been a gradual increase in the rate of hospitalizations for WHF with a more noticeable increase observed for HFpEF.

Generation of a Retina Reporter hiPSC Line to Label Progenitor, Ganglion, and Photoreceptor Cell Types.

Purpose: Early in mammalian eye development, VSX2, BRN3b, and RCVRN expression marks neural retinal progenitors (NRPs), retinal ganglion cells (RGCs), and photoreceptors (PRs), respectively. The ability to create retinal organoids from human induced pluripotent stem cells (hiPSC) holds great potential for modeling both human retinal development and retinal disease. However, no methods allowing the simultaneous, real-time monitoring of multiple specific retinal cell types during development currently exist. Methods: CRISPR/Cas9-mediated homology-directed repair (HDR) in hiPSCs facilitated the replacement of the VSX2 (Progenitor), BRN3b (Ganglion), and RCVRN (Photoreceptor) stop codons with sequences encoding a viral P2A peptide fused to Cerulean, green fluorescent protein, and mCherry reporter genes, respectively, to generate a triple transgenic reporter hiPSC line called PGP1. This was accomplished by co-electroporating HDR templates and sgRNA/Cas9 vectors into hiPSCs followed by antibiotic selection. Functional validation of the PGP1 hiPSC line included the ability to generate retinal organoids, with all major retinal cell types, displaying the expression of the three fluorescent reporters consistent with the onset of target gene expression. Disaggregated organoids were also analyzed by fluorescence-activated cell sorting and fluorescent populations were tested for the expression of the targeted gene. Results: Retinal organoids formed from the PGP1 line expressed appropriate fluorescent proteins consistent with the differentiation of NRPs, RGCs, and PRs. Organoids produced from the PGP1 line expressed transcripts consistent with the development of all major retinal cell types. Conclusions and Translational Relevance: The PGP1 line offers a powerful new tool to study retinal development, retinal reprogramming, and therapeutic drug screening.

Differential Pulmonary Rehabilitation Outcomes in Patients With and Without COPD: ROLE OF GENDER.

PURPOSE: Individuals with all forms of pulmonary disease are referred for pulmonary rehabilitation. This study examines pulmonary rehabilitation outcomes between individuals with chronic obstructive lung disease (COPD) and non-COPD disease and the impact of gender. METHODS: This is a retrospective study at a tertiary center. The primary endpoint was the difference in 6-min walk test distance. Secondary measurements included treadmill and NuStep minutes; biceps curls and front arm raises load; quality of life measured by the St George's Respiratory Questionnaire; and University of California San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) scores. RESULTS: Eighty patients were included: 38 men (23 COPD, 15 non-COPD) and 42 women (31 COPD, 11 non-COPD). There was a statistically significant improvement in 6-min walk test distances pre- to post-pulmonary rehabilitation for all participants, P = .0003. Although both the COPD and non-COPD groups demonstrated overall improvement (P < .0004 and P = .02, respectively), subgroup analysis showed no statistically significant change in the non-COPD group when divided by gender. There was a significant statistical improvement in lower and upper extremity strength in all participants. Only women with COPD showed a statistically significant improvement with respect to overall quality of life as measured by St. George's Respiratory Questionnaire (P = .01). Women showed significant improvement in their depression score, as well as a trend toward improvement in the University of California San Diego-Shortness of Breath Questionnaire, while only men with COPD showed any improvement in their sleep quality measured by the Pittsburgh Sleep Quality Index. CONCLUSIONS: Pulmonary rehabilitation results in different but improved outcomes regardless of gender or disease state.

A Rare but Reversible Cause of Hematemesis: "Downhill" Esophageal Varices.

"Downhill" varices are a rare cause of acute upper gastrointestinal bleeding and are generally due to obstruction of the superior vena cava (SVC). Often these cases of "downhill" varices are missed diagnoses as portal hypertension but fail to improve with medical treatment to reduce portal pressure. We report a similar case where recurrent variceal bleeding was initially diagnosed as portal hypertension but later found to have SVC thrombosis presenting with recurrent hematemesis. A 39-year-old female with history of end-stage renal disease presented with recurrent hematemesis. Esophagogastroduodenoscopy (EGD) revealed multiple varices. Banding and sclerotherapy were performed. Extensive evaluation did not show overt portal hypertension or cirrhosis. Due to ongoing bleeding requiring resuscitation, she underwent internal jugular (IJ) and SVC venogram in preparation for transjugular intrahepatic portosystemic shunt (TIPS), which demonstrated complete IJ and SVC occlusion. She underwent balloon angioplasty with stent placement across SVC occlusion with complete resolution of her varices and resolved hematemesis. "Downhill" varices are extremely rare, though previously well described. Frequently, patients are misdiagnosed with underlying liver disease. High index of suspicion and investigation of alternative causes of varices is prudent in those without underlying liver diseases. Prompt diagnosis and appropriate intervention can significantly improve morbidity and mortality.

Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids: A Two-Patient Case Series.

Acute fibrinous and organizing pneumonia (AFOP) is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

Temporary Endobronchial Stent as a Bridge to Corrective Surgery For Severe Kyphoscoliosis-associated Central-Airway Extrinsic Compression.

Kyphoscoliosis is known to compromise lung function, with the primary mechanism being reduced chest wall compliance with a resultant restrictive pulmonary physiology. Severe scoliosis can also cause extrinsic compression of the central airways, leading to recurrent respiratory infections, lobar atelectasis, and potentially acute respiratory failure. Definitive therapy is corrective surgery of the spine. However, patients with severe scoliosis are at a potentially high risk of perioperative pulmonary complications. To our knowledge, we report the first successful use of retrievable endobronchial stents as a bridge to corrective surgery for kyphoscoliosis-associated complete central-airway extrinsic compression in a patient who was considered as too high risk for surgical correction due to her respiratory status. After surgery, the stents were removed and our patient experienced sustained improvement in pulmonary function and the clinical respiratory status.

Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities including eosinophilia and/or atypical lymphocytosis, and extensive organ involvement. The drugs most often responsible for causing drug reaction with eosinophilia and systemic symptoms syndrome are anticonvulsants, antimicrobial agents and antipyretic or anti-inflammatory analgesics. Although azithromycin is widely prescribed in clinical practice, serious cutaneous reactions from this agent have been rarely described. We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin. CASE PRESENTATION: A 44-year-old previously healthy Caucasian man with history of tobacco use presented to his primary care physician with fever and productive cough. He was prescribed azithromycin, promethazine hydrochloride and dextromethorphan hydrobromide syrup. One week later, he developed a blistering erythematous rash over both hands, which over the next two weeks spread to involve nearly his entire body surface, sparing only his face. He was admitted to an outside hospital with signs of systemic inflammatory response syndrome and severe sepsis, presumably from a skin infection. Despite aggressive therapy he deteriorated, with worsening diffuse erythema, and was transferred to our institution. He developed multiple organ failure requiring ventilatory and hemodynamic support. Pertinent laboratory studies included a leukocytosis with a white blood cell count of 17.6 × 10(9)/L and 47% eosinophils. A skin biopsy showed evidence of spongiotic lichenoid dermatitis with eosinophils and neutrophils, compatible with a systemic drug-induced hypersensitivity reaction. Our patient was started on high-dose steroids and showed dramatic improvement within 48 hours. CONCLUSIONS: We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin exposure. Clinicians should be aware of this potentially devastating complication from this commonly prescribed medication.