Acute rejection post lung transplant.

PURPOSE OF REVIEW: To review what is currently known about the pathogenesis, diagnosis, treatment, and prevention of acute rejection (AR) in lung transplantation. RECENT FINDINGS: Epigenomic and transcriptomic methods are gaining traction as tools for earlier detection of AR, which still remains primarily a histopathologic diagnosis. SUMMARY: Acute rejection is a common cause of early posttransplant lung graft dysfunction and increases the risk of chronic rejection. Detection and diagnosis of AR is primarily based on histopathology, but noninvasive molecular methods are undergoing investigation. Two subtypes of AR exist: acute cellular rejection (ACR) and antibody-mediated rejection (AMR). Both can have varied clinical presentation, ranging from asymptomatic to fulminant ARDS, and can present simultaneously. Diagnosis of ACR requires transbronchial biopsy; AMR requires the additional measuring of circulating donor-specific antibody (DSA) levels. First-line treatment in ACR is increased immunosuppression (pulse-dose or tapered dose glucocorticoids); refractory cases may need antibody-based lymphodepletion therapy. First line treatment in AMR focuses on circulating DSA removal with B and plasma cell depletion; plasmapheresis, intravenous human immunoglobulin (IVIG), bortezomib, and rituximab are often employed.

Your note, your way: how to write an inpatient progress note accurately and efficiently as an intern.

A physician's progress note is an essential piece of documentation regarding key events and the daily status of patients during their hospital stay. It serves not only as a communication tool between care team members, but also chronicles clinical status and pertinent updates to their medical care. Despite the importance of these documents, little literature exists on how to help residents to improve the quality of their daily progress notes. A narrative literature review of English language literature was performed and summated to provide recommendations on how to write an inpatient progress note more accurately and efficiently. In addition, the authors will also introduce a method to build a personal template with the goal of extracting relevant data automatically to reduce clicks for an inpatient progress note in the electronic medical record system.

Inter-rater reliability and prognostic value of baseline Radiographic Assessment of Lung Edema (RALE) scores in observational cohort studies of inpatients with COVID-19.

OBJECTIVES: To reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes. SETTING: Hospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems. PARTICIPANTS: 425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set. PRIMARY AND SECONDARY OUTCOMES: We measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host-response biomarkers, SARS-CoV-2 RNA load and clinical outcomes. RESULTS: Inter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). In the discovery cohort, the required level of respiratory support at the time of CXR acquisition (supplemental oxygen or non-invasive ventilation (n=178); invasive-mechanical ventilation (n=234), extracorporeal membrane oxygenation (n=13)) was significantly associated with RALE scores (median (IQR): 20.0 (14.1-26.7), 26.0 (20.5-34.0) and 44.5 (34.5-48.0), respectively, p<0.0001). Among invasively ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, soluble receptor of advanced glycation end-products and soluble tumour necrosis factor receptor 1 (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted HR 1.04 (1.02-1.07), p=0.002). We replicated the significant associations of RALE scores with baseline disease severity and mortality in the independent validation data set. CONCLUSIONS: With a reproducible method to measure radiographic severity in COVID-19, we found significant associations with clinical and physiologic severity, host inflammation and clinical outcomes. The incorporation of radiographic severity assessments in clinical decision-making may provide important guidance for prognostication and treatment allocation in COVID-19.

Radiographic Assessment of Lung Edema (RALE) Scores are Highly Reproducible and Prognostic of Clinical Outcomes for Inpatients with COVID-19.

INTRODUCTION: Chest imaging is necessary for diagnosis of COVID-19 pneumonia, but current risk stratification tools do not consider radiographic severity. We quantified radiographic heterogeneity among inpatients with COVID-19 with the Radiographic Assessment of Lung Edema (RALE) score on Chest X-rays (CXRs). METHODS: We performed independent RALE scoring by ≥2 reviewers on baseline CXRs from 425 inpatients with COVID-19 (discovery dataset), we recorded clinical variables and outcomes, and measured plasma host-response biomarkers and SARS-CoV-2 RNA load from subjects with available biospecimens. RESULTS: We found excellent inter-rater agreement for RALE scores (intraclass correlation co-efficient=0.93). The required level of respiratory support at the time of baseline CXRs (supplemental oxygen or non-invasive ventilation [n=178]; invasive-mechanical ventilation [n=234], extracorporeal membrane oxygenation [n=13]) was significantly associated with RALE scores (median [interquartile range]: 20.0[14.1-26.7], 26.0[20.5-34.0] and 44.5[34.5-48.0], respectively, p<0.0001). Among invasively-ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, sRAGE and TNFR1 levels (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted hazard ratio 1.04[1.02-1.07], p=0.002). We validated significant associations of RALE scores with baseline severity and mortality in an independent dataset of 415 COVID-19 inpatients. CONCLUSION: Reproducible assessment of radiographic severity revealed significant associations with clinical and physiologic severity, host-response biomarkers and clinical outcome in COVID-19 pneumonia. Incorporation of radiographic severity assessments may provide prognostic and treatment allocation guidance in patients hospitalized with COVID-19.

Chest Radiograph Severity and Its Association With Outcomes in Subjects With COVID-19 Presenting to the Emergency Department.

BACKGROUND: Severity of radiographic abnormalities on chest radiograph in subjects with COVID-19 has been shown to be associated with worse outcomes, but studies are limited by different scoring systems, sample size, subject age, and study duration. Data regarding the longitudinal evolution of radiographic abnormalities and its association with outcomes are scarce. We sought to evaluate these questions using a well-validated scoring system (the Radiographic Assessment of Lung Edema [RALE] score) using data over 6 months from a large, multihospital health care system. METHODS: We collected clinical and demographic data and quantified radiographic edema on chest radiograph obtained in the emergency department (ED) as well as on days 1-2 and 3-5 (in those admitted) in subjects with a nasopharyngeal swab positive for SARS-CoV-2 by polymerase chain reaction (PCR) visiting the ED for coronavirus disease 2019 (COVID)-19-related complaints between March-September 2020. We examined the association of baseline and longitudinal evolution of radiographic edema with severity of hypoxemia and clinical outcomes. RESULTS: Eight hundred and seventy subjects were included (median age 53.6; 50.8% female). Inter-rate agreement for RALE scores was excellent (interclass correlation coefficient 0.84 [95% CI 0.82-0.87], P < .001). RALE scores correlated with hypoxemia as quantified by SpO2 /FIO2 (r = -0.42, P < .001). Admitted subjects had higher RALE scores than those discharged (6 [2-11] vs 0 [0-3], P < .001). An increase of RALE score ≥ 4 was associated with worse 30-d survival (P = .006). Larger increases in the RALE score were associated with worse survival. CONCLUSIONS: The RALE score was reproducible and easily implementable in adult subjects presenting to the ED with COVID-19. Its association with physiologic parameters and outcomes at baseline and longitudinally makes it a readily available tool for prognostication and early ICU triage, particularly in patients with worsening radiographic edema.

Improving Screening for Alpha-1 Antitrypsin Deficiency with Direct Testing in the Pulmonary Function Testing Laboratory.

Alpha-1 antitrypsin deficiency (AATD) is a common but highly underdiagnosed genetic disorder that may lead to chronic obstructive pulmonary disease (COPD), bronchiectasis, and liver disease. Early diagnosis is key to altering the course of disease as well as informing family members of potential risk. This randomized, prospective observational study compares the different testing modalities for AATD testing of at-risk patients initiated in the pulmonary function testing (PFT) laboratory. Providing a recommendation with a prescription for serologic testing, providing a finger-stick testing method (AlphaKit), and providing a buccal swab testing method (AlphaID) were compared to the community standard of referring the patient back to the PFT-ordering provider only. Results show that testing directly in the PFT laboratory has an odds ratio (OR) for completing testing of 35.14 (5.33 - 999.99), p-value of <0.0001, for buccal swab testing and an OR of 17.09 (2.58 - 729.99), p-value of 0.0002, for finger-stick testing compared to the community standard. Providing a prescription was no better than referral back to the PFT-ordering provider with an OR of 2.61(0.33 - 119.36), p-value of 0.6412. Resources needed to have testing performed by the Respiratory Therapy department were minimal with an average time of 1 to 5 minutes per patient tested. Causes of testing refusal were also identified. In conclusion, direct testing for AATD by respiratory therapists at the conclusion of PFT testing shows a significant improvement in rates of testing, especially with testing that utilizes buccal swab sample collection.

Do essential fatty acids have a role in the treatment of depression?

BACKGROUND: Complementary and alternative medicine (CAM) therapies are used more than conventional therapies by people with self-defined anxiety and depression. Preliminary evidence supports a hypothesis that low plasma concentration of essential fatty acids is associated with depression. Reported here is the result of a systematic review examining the therapeutic efficacy of essential fatty acids for depression. METHODS: Data sources included Medline, Psychinfo, AMED (Allied and Complementary Medicine), and Cochrane Controlled Trials Register databases searched from inception through September 2001. English language randomized controlled trials, controlled clinical trials, intervention studies, case control studies, reviews, and case reports of humans were selected, without limits for demographics or co-morbidities. Two abstractors independently evaluated each study, then reconciled findings. When possible, between group treatment effect size was noted or calculated. RESULTS: Six articles met inclusion criteria: one RCT, two reviews, and three case control trials. A common outcome measure among the case control trials allowed for direct comparison of effect sizes. CONCLUSIONS: The evidence implies promise of a treatment effect of omega-3 fatty acids for depression in adults; although a statement of definitive clinical efficacy is premature. Further study of essential fatty acids as independent and adjuvant therapy for adult depression is indicated, including more sophisticated investigation of dose-response in particular populations.

Ovarian teratoma and endometritis in a mare.

An 8-year-old Arabian mare was admitted for a large ovarian anovulatory follicle. A clinical diagnosis of ovarian tumor and endometritis was established. Histological examinations revealed an ovarian teratoma and a grade II endometritis. Three months after unilateral ovariectomy, the mare was confirmed pregnant and eventually gave birth uneventfully.

Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial.

OBJECTIVES: The aim of this study was to carry out a preliminary trial evaluating the effectiveness of homeopathy in the treatment of attention-deficit/hyperactivity disorder (ADHD). DESIGN: This work was a randomized, double-blind, placebo-controlled trial. SETTINGS/LOCATION: This study was conducted in a private homeopathic clinic in the Seattle metropolitan area. SUBJECTS: Subjects included children 6-12 years of age meeting Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for ADHD. INTERVENTIONS: Forty-three subjects were randomized to receive a homeopathic consultation and either an individualized homeopathic remedy or placebo. Patients were seen by homeopathic physicians every 6 weeks for 18 weeks. OUTCOME MEASURES: Outcome measures included the Conner's Global Index-Parent, Conner's Global Index- Teacher, Conner's Parent Rating Scale-Brief, Continuous Performance Test, and the Clinical Global Impression Scale. RESULTS: There were no statistically significant differences between homeopathic remedy and placebo groups on the primary or secondary outcome variables. However, there were statistically and clinically significant improvements in both groups on many of the outcome measures. CONCLUSIONS: This pilot study provides no evidence to support a therapeutic effect of individually selected homeopathic remedies in children with ADHD. A therapeutic effect of the homeopathic encounter is suggested and warrants further evaluation. Future studies should be carried out over a longer period of time and should include a control group that does not receive the homeopathic consultation. Comparison to conventional stimulant medication for ADHD also should be considered.

S-adenosylmethionine (SAMe) as treatment for depression: a systematic review.

PURPOSE: To assess the evidence evaluating S-adenosylmethionine (SAMe) supplementation as treatment for depression. METHODS: Searches of Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register were conducted from database inception through September 2001. Randomized controlled trials, controlled clinical trials, intervention studies, case-control studies, reviews, and case reports examining the evidence behind S-adenosylmethionine (SAMe) supplementation in depression among humans were selected. No limits were placed on study populations for demographics or co-morbidities. Only English language papers were abstracted and assessed for trial quality. Two abstractors independently evaluated each study, and then reconciled findings. As data were available, between group treatment effect size was noted or, as needed, calculated. RESULTS: Eleven articles met initial inclusion criteria; five intervention trials, two RCTs, two reviews, one controlled clinical trial, and one meta-analysis. Using the one common outcome measure among all the intervention studies and RCTs, the Hamilton Rating Scale for Depression, direct comparison of effect sizes was made. A favourable and significant between group effect was seen. CONCLUSION: All of the studies reviewed were short term, making translation to the clinical setting difficult. However, there appears to be a role for SAMe in the treatment of major depression in adults. Questions remain about mechanism of action, bioavailability, and absorption of oral SAMe. Further study of SAMe as independent and adjuvant therapy for major depression in adults is indicated.

The role for vitamin B-6 as treatment for depression: a systematic review.

BACKGROUND: Major depression is the leading cause of disability worldwide, and among the 10 most frequent indications for using alternative medicine therapies, especially dietary supplements. OBJECTIVE: To assess the evidence evaluating vitamin B-6 supplementation as treatment for depression. METHODS: Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register were searched from database inception through September 2001. All randomized controlled trials, controlled clinical trials, intervention studies, case-control studies, reviews, and case reports examining the evidence behind vitamin B-6 in depression among humans were selected. No limits were placed for demographics or co-morbidities. Only English language papers were abstracted and assessed for trial quality. Two abstractors independently evaluated each study, then reconciled findings. As data were available, between group treatment effect size was noted or, as needed, calculated. When studies reported outcome effects using multiple measures, data were abstracted to permit the greatest possible comparisons among papers. RESULTS: Ten articles met inclusion criteria; three reviews, one case report, five RCTs, and one intervention study. There was no common outcome measure among all studies, eliminating opportunity for direct comparison of effect sizes. As an alternate means of comparison, effects were plotted as they related to the null hypothesis. CONCLUSION: Viewed as a whole, meaningful treatment effect of vitamin B-6 for depression in general was not apparent. However, examination of papers addressing depression in pre-menopausal women only, reveals a consistent message about the value of using vitamin B-6 supplementation. Further study of vitamin B-6 as independent and adjuvant therapy for hormone related depression in women is indicated.

About hemispheric differences in the processing of temporal intervals.

The purpose of the present study was to identify differences between cerebral hemispheres for processing temporal intervals ranging from .9 to 1.4 s. The intervals to be judged were marked by series of brief visual signals located in the left or the right visual field. Series of three (two standards and one comparison) or five intervals (four standards and one comparison), marked by sequences of 4 or 6 signals, were compared. While discrimination, as estimated by d', was significantly better in the 4-standard than in the 2-standard condition when stimuli were presented in the left visual field (LVF), this number-of-standard effect on discrimination varied with the difficulty levels when the signals were presented in the LVF. Moreover, the discrimination levels were constant for the different base durations with stimuli presented in the LVF, but not with stimuli presented in the right visual field. This article discusses the implication of these findings for the study of hemispheric dominance for temporal processing and for a single-clock hypothesis.

The evidence base for complementary and alternative medicine: methods of Evidence Mapping with application to CAM.

BACKGROUND: There is widespread concern regarding the adequacy of evidence for specific practices under the rubric of "complementary and alternative medicine" (CAM). OBJECTIVE: To map the evidence pertaining to many commonly used CAM practices. DESIGN: In 2000, the Yale Prevention Research Center was funded by the Centers for Disease Control and Prevention to conduct a "systematic review" of the evidence underlying CAM. The investigative team, working in collaboration with CAM practitioners, developed a systematic and replicable 9-step process termed evidence mapping. The process stipulates means for specifying the boundaries of the subject to be mapped in MeSH terms, and the characteristics used to situate retrieved articles in the overall map of evidence. SETTING: Yale Prevention Research Center, Derby, CT. RESULTS: Steps completed thus far have led to the identification of over 4,000 papers distributed across 207 condition-treatment pairs. Of these pairs, 58% (n = 121) have been studied with one or more RCTs (1,070 total RCTs), and 23% (n = 47) have been the subject of one or more meta-analyses (86 total meta-analyses). Thirty-seven condition/treatment pairs (18%) had no identifiable supporting studies. CONCLUSIONS: The novel methods of evidence mapping reported are useful and practical in characterizing the extent, distribution, and methodologic quality of research pertaining to a broad topic in medicine. Applied to CAM, they suggest that summary judgments about the quantity or quality of underlying evidence are overly simplistic.