Severe Dyspnea Research Articles

Mild Encephalitis with Reversible Splenial Lesion Associated with COVID-19

Coronavirus disease-2019 (COVID-19) is an emerging pandemic disease with high morbidity and mortality. The area primarily affected in COVID-19 is the pulmonary system, where the most destructive effect occurs. Symptoms range from asymptomatic illness to mild-to-moderate (mild pneumonia), severe (dyspnea, hypoxia), and critical illness symptoms (acute respiratory distress syndrome, respiratory failure, shock, or multiorgan system dysfunction) in patients with COVID-19. Neurological manifestations, such as acute ischemic stroke, intracerebral hemorrhage, cerebral venous sinus thrombosis, conscious disturbance, febrile seizures, convulsions, mental status change, and encephalitis are observed in severe patients. Mild encephalitis/encephalopathy with reversible splenial (MERS) lesions is a clinicoradiological diagnosis that is associated with a prominent reversible lesion in the corpus callosum (SCC) splenium, infectious agent, and mild encephalopathy. In this case report, the key clinical and radiological features of MERS were highlighted in an adult patient presented to the emergency department with nausea, vomiting, and unconsciousness and admitted to the neurology clinic due to diffusion restriction in the SCC splenium.

Second-Hand Smoke Exposure Associated with Risk of Respiratory Symptoms, Asthma, and COPD in 20,421 Adults from the General Population.

RationaleIndividuals exposed to second-hand smoking may be more susceptible to asthma and chronic obstructive pulmonary disease (COPD). We investigated the risk of respiratory symptoms, asthma, and COPD in adults exposed to second-hand smoking at different stages of life in the general population.MethodsWe identified individuals who had been exposed to second-hand smoking in childhood only, adulthood only, or lifelong in a cohort of 20,421 adults from the Danish General Suburban Population Study and recorded respiratory symptoms, lung function, asthma, and COPD as outcomes.ResultsAmong 20,421 adults from the general population, 2,551 (12%) had been lifelong exposed to second-hand smoking, 459 (2%) had been exposed in adulthood only, and 13,998 (69%) had been exposed in childhood only; the mean ages of the three groups were 54 years, 55 years, and 57 years, respectably, compared with 56 years in non-exposed individuals (P<0.001). Equivalent values for the prevalence of current smoking were 25%, 20%, and 18% versus 12% (P<0.001). After adjustment for age, smoking, and sex, the odds ratios for wheezing, severe dyspnoea, cough on exertion, and asthma increased as a function of second-hand smoke exposure (Ps≤0.004); individuals who had been exposed to second-hand smoking lifelong, in adulthood only, or in childhood only versus non-exposed had increased odds ratios for wheezing of 1.62 (95% CI=1.41–1.87), 1.50 (1.15–1.94), and 1.16 (1.04–1.30). Corresponding values were 2.08 (1.52–2.85), 2.05 (1.22-3-44), and 1.23 (0.95–1.59) for severe dyspnoea, 1.56 (1.33–1.83), 1.53 (1.15–2.02), and 1.19 (1.05–1.35) for cough on exertion, 1.36 (1.14–1.63), 1.49 (1.09–2.05), and 1.13 (0.99–1.30) for asthma, and 1.24 (1.03–1.48), 1.25 (0.90–1.74), and 1.09 (0.96–1.24) for COPD. The population attributable fractions of asthma and COPD due to lifelong second-hand smoke exposure were 4.3% and 2.9%.ConclusionIndividuals exposed to lifelong second-hand smoking have increased risks of respiratory symptoms, asthma, and COPD, and may account for 4.3% and 2.9% of people with asthma and COPD in the general population.

WHEN SHOULD CANNABIS CROSS YOUR MIND? A CASE REPORT OF ANAPHYLACTIC SHOCK INDUCED BY MARIJUANA-TOMATO CROSS REACTIVITY

TOPIC: Allergy and Airway TYPE: Medical Student/Resident Case Reports INTRODUCTION: With the increased prevalence of recreational and medical marijuana use throughout the United States, patients with severe food allergies are particularly vulnerable to severe and devastating allergic reactions from its use. Nonspecific lipid transfer proteins, which can be found on the Cannabis sativa leaf, are also found on a variety of fruits and legumes, providing a mechanism for cross-reactivity in those susceptible to certain food allergies. CASE PRESENTATION: We present a case of a 35-year-old female with a past medical history of OSA on CPAP, hypertension, and anxiety with complaints of shortness of breath and wheezing. The night prior, she attested to having a glass of wine and smoking half of a marijuana joint. Shortly after she smoked, she began to complain of an itchy throat and an itching sensation throughout her body. She perceived the symptoms as only mild and went to bed with her CPAP machine, hoping that her symptoms would resolve spontaneously. Hours later, she suddenly woke up with severe dyspnea and respiratory distress, prompting her to call EMS. Initial vitals were BP 120/62, HR 75, RR 28, and SpO2 98% on non-rebreather mask. Her chemistry profile was unremarkable with normal renal and liver indices. EKG showed normal sinus rhythm with a ventricular rate of 86 bpm. Her listed allergies included angioedema to Lisinopril, urticaria to aromatic oils, and hives to tomatoes. Family history was non-contributory. Chest X-ray showed no acute pulmonary findings. On physical exam, she was in severe respiratory distress and barely able to complete any sentences. There were no adventitious sounds on auscultation of her lung fields, although severe upper airway stridor was appreciated. Diffuse urticaria was also noted over her extremities. She required urgent endotracheal intubation and mechanical ventilation for severe respiratory distress and upper airway edema, attributed to severe anaphylaxis. At the time, the precipitating agent that caused her to clinically deteriorate was unclear. Two doses of epinephrine IM, benadryl 50 mg IV, and Solumedrol 125 mg IV were administered. Within 24 hours, the patient's airway edema markedly improved and she passed a leak test prior to extubation. She was successfully discharged home the following day on a steroid taper and H2 inhibitor. DISCUSSION: Review of literature demonstrates a well established cross reactivity between the cannabis sativa leaf and multiple plant-food allergens, including tomatoes, peaches, and apples (1). Patients who are sensitized to non-specific lipid transfer proteins, found on the surface of these and other fruits, may develop a cross-reaction when marijuana is ingested, leading to a wide range of allergic reactions (2). CONCLUSIONS: A thorough history, physical, and review of potential cross-reactions between a patient's known allergies & recently ingested foods or substances is imperative to an accurate diagnosis. REFERENCE #1: Decuyper, I. I., Van Gasse, A. L., Cop, N., Sabato, V., Faber, M. A., Mertens, C., ... & Ebo, D. G. (2017). Cannabis sativa allergy: looking through the fog. Allergy, 72(2), 201-206. REFERENCE #2: Azofra, J., Berroa, F., Gastaminza, G., Saiz, N., Gamboa, P. M., Vela, C., ... & Goikoetxea, M. J. (2016). Lipid transfer protein syndrome in a non-Mediterranean area. International archives of allergy and immunology, 169(3), 181-188. DISCLOSURES: No relevant relationships by Maie Abdullah, source=Web Response no disclosure on file for Bhavinkumr Dalal; No relevant relationships by Kareem Ebeid, source=Web Response

IS ACUTE FIBRINOUS AND ORGANIZING PNEUMONIA AN EMERGING CAUSE OF DIFFUSE ALVEOLAR HEMORRHAGE?

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a rare and poorly understood form of interstitial lung disease that can present either acutely or insidiously. Among the acute manifestations of AFOP, diffuse alveolar hemorrhage (DAH) has only been described once before in the literature. CASE PRESENTATION: A 25 year old male with a history of end stage renal disease secondary to bilateral posterior urethral valves (on hemodialysis) and cutaneous neutrophilic dermatosis (Sweet syndrome) presented with the abrupt onset of severe dyspnea. Given concern for flash pulmonary edema on initial chest radiograph (Figure 1), he was placed on a nitroglycerine drip and underwent emergent hemodialysis with ultrafiltration. He subsequently developed rapidly progressive acute hypoxic respiratory failure with worsening pulmonary infiltrates (Figure 2) requiring emergent intubation and mechanical ventilation. Copious bloody secretions were noted during intubation, and the patient required multiple blood transfusions following admission. Despite mechanical ventilation with paralysis and proning, the patient developed severe adult respiratory distress syndrome with a P:F ratio nadir of 74. Chest CT revealed diffuse severe consolidative lung injury of unclear etiology (Figure 3). Bronchoscopy with serial aliquots on bronchoalveolar lavage confirmed the presence of diffuse alveolar hemorrhage. The patient’s condition improved rapidly with initiation of systemic glucocorticoids, and he was subsequently extubated on hospital day 5. Shortly after discharge home, the patient was readmitted with recurrent severe acute hypoxic respiratory failure in the setting of tapering his glucocorticoids, but he was successfully extubated within 24 hours following reinitiation of high-dose systemic glucocorticoids. Bronchoscopically-guided cryobiopsy during this admission revealed a diagnosis of AFOP, and the patient was ultimately discharged home with plans for a prolonged course of steroids and possible transition to steroid-sparing agents. DISCUSSION: Further investigations are needed to determine whether AFOP represents a distinct clinical entity, or rather the sequelae of concomitant inflammatory or autoimmune processes such as those present in this patient. Regardless of the etiology, data from case reports suggest that AFOP can be highly responsive to systemic glucocorticoids and other forms of immunosuppression. Delay in diagnosis, however, remains a significant barrier to the treatment of AFOP and portends poor prognosis in the acute form of this illness. CONCLUSIONS: The addition of this case to the literature suggests that DAH may represent an emerging manifestation of AFOP. Prompt recognition of this rare and heterogeneous disease process is imperative, as increasing evidence suggests favorable outcomes with early initiation of systemic glucocorticoids. REFERENCE #1: Crowley N, Sessler C, Miller K, Robila V, Debesa, O. Relapsing acute fibrinous and organizing pneumonia complicated by diffuse alveolar hemorrhage. Chest. 2018;154(4)(suppl):409A-410A. doi: 10.1016/j.chest.2018.08.375. REFERENCE #2: Lee JH, Yum HK, Jamous F, Santos C, Campisi A, Surani S, Lococo F, Goo JM, Yoon SH. Diagnostic procedures and clinico-radiological findings of acute fibrinous and organizing pneumonia: a systematic review and pooled analysis. Eur Radiol. 2021 Mar 31. doi: 10.1007/s00330-021-07868-z. Epub ahead of print. REFERENCE #3: Santos C, Oliveira RC, Serra P, Baptista JP, Sousa E, Casanova P, Pimentel J, Carvalho L. Pathophysiology of acute fibrinous and organizing pneumonia - Clinical and morphological spectra. Pathophysiology. 2019 Sep-Dec;26(3-4):213-217. doi: 10.1016/j.pathophys.2019.04.001. DISCLOSURES: No relevant relationships by Andrew Davis, source=Web Response No relevant relationships by Nathan Sandbo, source=Web Response

Stiff person syndrome and prior temporal lobectomy: Is it a case of misplaced autoimmunity?

AbstractBackgroundStiff person syndrome (SPS) is a rare autoimmune disorder, characterized by progressive rigidity and muscle spasms affecting the axial and limb muscles. Anti‐glutamic acid decarboxylase (anti‐GAD65) antibodies are linked to pathogenesis of both epilepsy and SPS. We aim to highlight epilepsy surgery as a potential trigger for development of SPS.Case presentationA 35‐year‐old female with medically refractory temporal lobe epilepsy underwent right amygdala‐hippocampectomy in 2009. The patient was seizure‐free until 2019 when she developed spells of severe muscle spasms, palpitations, dyspnea, and restlessness. Examination revealed increased spasticity in bilateral lower extremities, a wide based gait, and hyperreflexia with crossed adductor sign and bilateral Babinski sign. Serum and cerebrospinal fluid (CSF) labs were obtained, and two typical spells occurred during continuous video electroencephalogram (cvEEG) monitoring. Typical spells did not correlate with seizure activity on cvEEG. CSF analysis showed normal opening pressure, Gram stain, culture, cell count, protein, and glucose. Serum and CSF GAD65 antibody levels were 5153 nMol/L and 53 nMol/L, respectively, along with 14 oligoclonal bands in CSF. Diagnosis of SPS was made. Treatment with diazepam caused improvement in spells and myalgia.ConclusionThe diagnosis of SPS can be delayed in a patient with history of epilepsy. Although SPS and epilepsy are often linked by anti‐GAD antibodies as common etiology, it is possible that epilepsy surgery might be a trigger for development of SPS in a small subset. Development of autoimmunity to neuronal GAD65 protein, exposed during surgery, is suspected in pathogenesis.

Characterization of Symptoms after Radical Prostatectomy and Their Relation to Postoperative Complications.

Many patients will experience symptoms in the initial days after radical prostatectomy (RP), but early patient-reported symptoms have not been well characterized. Our objective was to illustrate the pattern of symptoms experienced after RP and the relation of severe symptoms to postoperative complications. In 2016, electronic patient-reported symptom monitoring began at our institution's ambulatory surgery center. We retrospectively reviewed patients treated with minimally invasive RP who were sent a daily questionnaire completed using a web interface until postoperative day 10. Severe symptoms automatically generate a "yellow alert," which messages the clinic, while very severe symptoms generate a "red alert," additionally prompting the patient to call. We summarized rates of moderate-to-very severe symptoms and fit local polynomial regressions. We compared rates of 30-day or 90-day complications (grade ≥2) based on the presence of alert symptoms. Of 2,266 men undergoing RP, 1,942 (86%) completed surveys. Among moderate-to-very severe symptom levels, pain (72%) and dyspnea (11%) were most common. Pain, nausea and dyspnea consistently decreased over time; fever and vomiting had a flat pattern. In patients experiencing red-alert symptoms, we observed a higher risk of 30-day complications, but rates were low and differences between groups were nonsignificant (2.9% vs 1.9%; difference 1.1%; 95% CI -1.3-3.5; p=0.3). Results were similar examining 90-day complications. While symptoms are common after RP, substantial improvements occur over the first 10 days. Severe or very severe symptoms conferred at most a small absolute increase in complication risk, which should be reassuring to patients and clinicians.

Вплив екологічних факторів на маніфестацію респіраторних захворювань

Вперше в Україні в Харківському регіоні в 2015–2017 роках виконано IV фазу Міжнародної програми ISAAC. Було роздано 6330 анкет; у програмі взяли участь 6146 (97 %) школярів. Респіраторні скарги виявлені у 12,8 %: серед дітей 6–7 років — 13,2 %, 13–14 років — 12,4 %. Для виявлення динаміки поширення респіраторних симптомів проведено порівняння з даними І фази ISAAC (Огнєв В.А., 1998) — за останні 19 років поширеність респіраторних симптомів знизилася у 1,6 раза серед дітей молодшого шкільного віку, у 2 рази — в підлітковому віці. Дослідження проведено в 8 районах Харківської області (Лозівському, Куп’янському, Вовчанському, Богодухівському, Сахновщанському, Барвінківському, Дергачівському, Нововодолазькому), що відрізняються екологічними характеристиками середовища. В екологічно забруднених районах вище поширеність wheezing у 1,4 раза, симптомів астми фізичного напруження — у 1,9 раза та у 3,4 раза частіше відзначаються тяжкі напади задишки, що порушують нічний сон. Дослідження спрямовано на удосконалення профілактики бронхіальної астми в дитячій популяції Харківської області.

Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD)

BackgroundRefractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine.MethodsWe describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 < 50%, mMRC ≥ 3, on optimal standard therapy) will be included.DiscussionEvidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD.Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363.

Post-ablation Dyspnea a Case Report to Highlight the Differential Diagnoses

The diagnosis of post-cardiac ablation pericarditis is difficult as it requires the exclusion of the more common causes of chest pain, but in the right setting, non-invasive diagnostic tools are adequate. Here we present the case of a 60-year-old man who underwent atrial fibrillation ablation and subsequently developed severe mid-sternal chest pain and dyspnea one day later without significant electrocardiographic findings, a mildly elevated troponin T, and elevation of the right hemidiaphragm. The patient was managed conservatively. A two-dimensional transthoracic echocardiogram showed no regional wall motion abnormalities, significant transvalvular gradients, but showed minimal pericardial effusion. A sniff test was negative for diaphragmatic paralysis. After the diagnosis, the patient’s symptoms resolved with non-steroidal anti-inflammatory drugs and colchicine. This case of pericarditis after cardiac ablation highlights the possible differential diagnosis when confronted with post-ablation cardiac symptoms. Despite the classic presentation, the electrocardiogram showed no significant ST/PR changes. In the right clinical setting, non-invasive imaging may be appropriate management.

突然の心不全を契機に発見された基礎疾患のない若年者の褐色細胞腫の1例(A case of pheochromocytoma in young patient without cardiovascular risk factors that found out due to sudden heart failure)

要旨 30代女性。呼吸苦で救急受診し，胸部X線で全肺野スリガラス陰影，computed tomographyで肺水腫・右副腎腫瘍を認めた。経胸壁心エコーで推定左室駆出率 約30%・全周性壁運動低下を認め，急性心不全として緊急入院した。人工呼吸管理後，呼吸苦や頻呼吸は消失し，酸素化も速やかに改善した。第2病日，胸部X線・経胸壁心エコー所見も正常となり抜管した。入院時病態は不明のまま，第9病日退院した。入院時，偶発的に発見された右副腎腫瘍から褐色細胞腫による肺水腫・心機能低下を考慮し，退院後に精査された。血中カテコラミン濃度・123I–MIBG（metaiodobenzylguanidine）シンチグラフィ・クロニジン負荷試験などより褐色細胞腫と診断された。その後，右副腎摘出術により寛解した。入院時の症状は褐色細胞腫から多量に分泌されたカテコラミンによる心不全であったと考えられた。

Severe tachypnoea and dyspnoea due to physiological hyperventilation in pregnancy.

Physiological hyperventilation and dyspnoea in pregnancy are well-established phenomena and commonly lead to a chronic respiratory alkalosis with compensatory renal excretion of bicarbonate. However, the underlying mechanism of dyspnoea during normal pregnancy remains largely undefined. Increasing progesterone levels are a primary factor leading to increased respiratory drive to ensure the rising metabolic demands of the pregnancy are met. Dyspnoea symptoms typically begin in the first or second trimester, are mild, and do not interfere with activities of daily living. We report the case of a 35-year-old female with severe physiological hyperventilation of pregnancy presenting with profound dyspnoea, tachypnoea, and presyncope from 18 weeks of gestation until delivery. Subsequent investigations revealed no identifiable underlying pathology. There remain limited reports of such severe physiological hyperventilation of pregnancy. This case highlights interesting questions regarding the respiratory physiology of pregnancy and underlying mechanisms.

Successful Chemotherapy of an Acute Myeloid Leukemia Case Infected with SARS-CoV-2

Introduction: New coronavirus or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in Wuhan, China at the end of 2019. There is not enough data for managing acute myeloid leukemia patients with concomitant infection with SARS-COV-2. This is a report of a unique case with acute leukemia and SARS-CoV-2 infection that recovered from both. Case Presentation: a 44-year man was admitted with fever and sweating. He was treated with broad-spectrum antibiotics. Pancytopenia was detected and a bone marrow biopsy revealed acute leukemia. During his management, the patient developed a dry cough. He was transferred to our center for chemotherapy. Chest CT scan revealed bilateral peripheral patchy ground-glass infiltrations, indicating SARS-CoV-2 infection. Two weeks later, after antiviral and broad-spectrum antibiotic therapy, he developed severe dyspnea and became bedridden. Modified chemotherapy was started. He rapidly recovered, and his leukemia developed complete remission. Conclusions: We presented a successful chemotherapy of an acute leukemia patient that was simultaneously infected with COVID-19. Chemotherapy should be done for acute leukemia judiciously without delay in patients infected with SARS-CoV-2 infection.

Characteristics of COVID-19 Pneumonia Survivors With Resting Normoxemia and Exercise-Induced Desaturation.

Survivors of coronavirus disease 2019 (COVID-19) associated pneumonia may show exercise-induced desaturation. We wondered whether these individuals show physiologic and symptom characteristics similar to individuals with chronic respiratory diseases with exercise-induced desaturation, namely COPD or interstitial lung diseases (ILD). We evaluated lung function, exercise capacity, and symptoms in these individuals compared with individuals with COPD or ILD and exercise-induced desaturation. Survivors of COVID-19 associated pneumonia (study individuals), normoxemic at rest with exercise-induced desaturation, underwent assessment of dyspnea, dynamic lung volumes, carbon monoxide diffusion capacity, and the 6-min walk test. Data of individuals with COPD or with ILD and exercise-induced desaturation were also retrospectively analyzed. FVC was lower in individuals with COVID-19 or ILD than in those with COPD. Individuals who had COVID-19 walked < 70% of predicted and, as a whole, had a 6-min walk test performance similar to individuals with ILD but walked significantly less, showed more severe leg fatigue and dyspnea during exercise, and more exercise-induced desaturation than individuals with COPD. Survivors of COVID-19 associated pneumonia, who were normoxemic at rest with exercise-induced desaturation, had alterations in lung function, exercise capacity, and symptoms similar to individuals with ILD but more severe than individuals with COPD and exercise-induced desaturation.

Focal Myocarditis after Mild COVID-19 Infection in Athletes

COVID-19 infection in athletes usually has a milder course, but in the case of complications, myocarditis and even sudden cardiac death may occur. We examined an athlete who felt symptoms upon returning to training after asymptomatic COVID-19 infection. Physical, laboratory, and echocardiography findings were normal. The cardiopulmonary exercise test was interrupted at submaximal effort due to severe dyspnea in the presence of reduced functional capacity in comparison to previous tests. Cardiac magnetic resonance (CMR) detected the focal myocarditis. After three months of recovery, CMR still revealed the presence of focal myocarditis and the persistence of decreased functional capacity. This case raises the question of screening athletes even after asymptomatic forms of COVID-19 infection.

In vivo performance of decellularized tracheal grafts in the reconstruction of long length tracheal defects: Experimental study

The repair of long-segment tracheal lesions remains an important challenge. Nowdays no predictable and dependable substitute has been found. Decellularized tracheal scaffolds have shown to be a promising graft for tracheal transplantation, since it is non-immunogenic. Evaluate in vivo decellularized tracheal allografts performance to replace long tracheal segment. Forty-five swines underwent surgery as follows: Fifteen trachea donors and 30 receptors of decellularized trachea allografts. The receptors were randomly divided in five groups (n = 6). In groups I and II, donor trachea segment was decellularized by 15 cycles with sodium deoxycholate and deoxyribonuclease, in group II, the allograft was reinforced with external surgical steel wire. Groups, III, IV, and V decellularization was reduced to seven cycles, supplemented with cryopreservation in group IV and with glutaraldehyde in group V. A 10 rings segment was excised from the receptor swine and the decellularized trachea graft was implanted to re-establish trachea continuity. Both decellularization cycles caused decreased stiffness. All trachea receptors underwent euthanasia before the third post-implant week due to severe dyspnea and trachea graft stenosis, necrosis, edema, inflammation, hemorrhage, and granulation tissue formation in anastomotic sites. Histologically all showed total loss of epithelium, separation of collagen fibers, and alterations in staining. Both decellularization techniques severely damaged the structure of the trachea and the extracellular matrix of the cartilage, resulting in a no functional graft, in spite of the use of surgical wire, cryopreservation or glutaraldehyde treatment. An important drawback was the formation of fibrotic stenosis in both anastomosis.

A Comparison of Pathogenicity and Virulence of Three Porcine Circovirus Type 2 (PCV2) Genotypes (a, b, and d) in Pigs Singularly Inoculated with PCV2 and Dually Inoculated with Mycoplasma hyopneumoniae and PCV2.

The objective of this study was to compare the virulence of three different porcine circovirus type 2 (PCV2) genotypes (PCV2a, PCV2b, and PCV2d) in pigs infected with either one of these three PCV2 genotypes versus pigs dually inoculated with Mycoplasma hyopneumoniae and PCV2. Pigs were inoculated intratracheally with M. hyopneumoniae at 4 weeks of age followed by another intranasal inoculation at 6 weeks of age with one of three PCV2 genotypes. Dual infection with two pathogens produced moderate and severe dyspnea, lethargy, and reduced weight gain in pigs regardless of the PCV2 genotype evaluated compared with pigs only inoculated with PCV2. The overall levels of PCV2d viremia and severity of lymphoid lesions, and PCV2-antigen within lymphoid lesions were significantly higher in pigs dually inoculated with M. hyopneumoniae/PCV2d when compared with all other dually inoculated groups. The level of PCV2 viremia and the production of PCV2-associated lymphoid lesions did not differ significantly among PCV2a, PCV2b, and PCV2d single-inoculated pig groups. The results of this study demonstrated that M. hyopneumoniae potentiated the replication of PCV2d more than it did with the other PCV2 genotypes as measured by lymphoid lesion severity.

Development, evaluation and use of COVID-19 vaccines in older adults: Preliminary principles for the pandemic and beyond.

Development, evaluation and use of COVID-19 vaccines in older adults: Preliminary principles for the pandemic and beyond.

Prednisone combined with letrozole reduced risk of ovarian hyperstimulation syndrome (OHSS) in women undergoing long-term gonadotropin-releasing hormone analog treatment.

Ovarian hyperstimulation syndrome (OHSS) is a severe disease that can lead to serious complication. Letrozole has been applied during controlled ovarian hyperstimulation (COH) to reduce the rate of OHSS in women undergoing long-term Gonadotropin-releasing Hormone Analog (GnRHa) treatment for assisted fertility. Prednisone can prevent vasodilatation and increased vascular permeability, which is common during OHSS. However, few studies have evaluated the combined effect of letrozole and prednisone in preventing severe OHSS and is the aim of our retrospective study of patients receiving GnRHa treatment. A total of 296 women who accepted autologous in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included in this retrospective study. There were three groups: 146 women had letrozole, including letrozole alone (LE group, n=60) and letrozole with prednisone (LE + Pre group, n=86), and 150 women had no treatment (C group). Severe OHSS was diagnosed according to clinical evidence of hydrothorax, severe dyspnea, oliguria/anuria, and intractable nausea/vomiting. The addition of prednisone to letrozole successfully reduced the occurrence rate of severe OHSS than those women administered letrozole alone (55.0% vs. 70.6%, P=0.022). However, the ongoing pregnancy rate was lower in the LE + Pre group than that in the LE-alone group (64.3% vs. 87.0%, P=0.025). Surprisingly, progesterone level on the trigger day (>0.895 ng/mL) is a strong predictor for pregnancy failure with a specificity of 68.3% and sensitivity of 65.7% in the LE-alone group. Treatment with a combination of letrozole and prednisone may lower the rate of severe OHSS in women with prolonged gonadotropin-releasing hormone agonist protocol during assisted fertility treatment. When the progesterone level on trigger day is over 0.895 ng/mL, letrozole treatment may negatively affect clinical pregnancy.

Clinical Strains of Pseudomonas aeruginosa Secrete LasB Elastase to Induce Hemorrhagic Diffuse Alveolar Damage in Mice.

BackgroundAcute lung injury and acute respiratory distress syndrome (ALI/ARDS) are most often caused by bacterial pneumonia and characterized by severe dyspnea and high mortality. Knowledge about the lung injury effects of current clinical bacterial strains is lacking. The aim of this study was to investigate the ability of representative pathogenic bacteria isolated from patients to cause ALI/ARDS in mice and identify the major virulence factor.MethodsSeven major bacterial species were isolated from clinical sputum and unilaterally instilled into the mouse airway. A histology study was performed to determine the lung injury effect. Virulence genes were examined by PCR. Sequence types of P. aeruginosa strains were identified by MLST. LC-MS/MS was used to analysis the bacterial exoproducts proteome. LasB was purified through a DEAE-cellulose column, and its toxicity was tested both in vitro and in vivo.ResultsStaphylococcus aureus, Streptococcus pneumoniae, Streptococcus agalactiae, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were randomly separated and tested 3 times. Among them, gram-negative bacteria have much more potential to cause acute lung injury than gram-positive bacteria. However, P. aeruginosa is the only pathogen that induces diffuse alveolar damage, hemorrhage and hyaline membranes in the lungs of mice. The lung injury effect is associated with the excreted LasB elastase. Purified LasB recapitulated lung injury similar to P. aeruginosa infection in vivo. We found that this was due to the powerful degradation effect of LasB on the extracellular matrix of the lung and key proteins in the coagulation cascade without inducing obvious cellular apoptosis. We also report for the first time that LasB could induce DIC-like coagulopathy in vitro.ConclusionP. aeruginosa strains are most capable of inducing ALI/ARDS in mice among major clinical pathogenic bacteria tested, and this ability is specifically attributed to their LasB production.

Associations of Medication Regimen Complexity with COPD Medication Adherence and Control.

IntroductionMedication adherence is often low among people with chronic obstructive pulmonary disease (COPD) and medication regimen complexity may be a contributing factor. In this study, we sought to examine the role of medication regimen complexity in COPD medication adherence among patients with multimorbidity.MethodsWe performed cross-sectional analysis of data on COPD patients in primary care and pulmonary practices in New York City and Chicago (n=400). Regimen complexity was represented by the medication regimen complexity index (MRCI) and simple medication count. Adherence was measured by self-report and inhaler dose counts. Disease control measures included the COPD severity score (COPDSS) and the Medical Research Council (MRC) severity index.ResultsMean age of study participants was 69 years, 66% had MRC grades 4 or 5, and 45% had low medication adherence. MRCI scores did not differ significantly between those with and without adequate medication adherence. Patients with higher MRCI scores were more likely to have severe COPD (OR 5.00, 95% CI 1.46–17.1, p=0.01) and dyspnea grades 3 or 4 (OR 2.27, 95% CI 1.03–5.03, p=0.04). Significant associations of medication count with COPD severity were also observed.DiscussionThese findings demonstrate that among patients with COPD and comorbid hypertension and diabetes, higher medication regimen complexity is associated with worse COPD control but not with COPD medication adherence.