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"Silverman, Martin (Martin A.)"
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My tooth is loose!
When Georgie announces he has a loose tooth, all of his friends have advice to offer him, but none of it is appealing.
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Implications of Race Adjustment in Lung-Function Equations
Adjustment for race is discouraged in lung-function testing, but the implications of adopting race-neutral equations have not been comprehensively quantified.
We obtained longitudinal data from 369,077 participants in the National Health and Nutrition Examination Survey, U.K. Biobank, the Multi-Ethnic Study of Atherosclerosis, and the Organ Procurement and Transplantation Network. Using these data, we compared the race-based 2012 Global Lung Function Initiative (GLI-2012) equations with race-neutral equations introduced in 2022 (GLI-Global). Evaluated outcomes included national projections of clinical, occupational, and financial reclassifications; individual lung-allocation scores for transplantation priority; and concordance statistics (C statistics) for clinical prediction tasks.
Among the 249 million persons in the United States between 6 and 79 years of age who are able to produce high-quality spirometric results, the use of GLI-Global equations may reclassify ventilatory impairment for 12.5 million persons, medical impairment ratings for 8.16 million, occupational eligibility for 2.28 million, grading of chronic obstructive pulmonary disease for 2.05 million, and military disability compensation for 413,000. These potential changes differed according to race; for example, classifications of nonobstructive ventilatory impairment may change dramatically, increasing 141% (95% confidence interval [CI], 113 to 169) among Black persons and decreasing 69% (95% CI, 63 to 74) among White persons. Annual disability payments may increase by more than $1 billion among Black veterans and decrease by $0.5 billion among White veterans. GLI-2012 and GLI-Global equations had similar discriminative accuracy with regard to respiratory symptoms, health care utilization, new-onset disease, death from any cause, death related to respiratory disease, and death among persons on a transplant waiting list, with differences in C statistics ranging from -0.008 to 0.011.
The use of race-based and race-neutral equations generated similarly accurate predictions of respiratory outcomes but assigned different disease classifications, occupational eligibility, and disability compensation for millions of persons, with effects diverging according to race. (Funded by the National Heart Lung and Blood Institute and the National Institute of Environmental Health Sciences.).
Journal Article
The neural processing of negative emotion postpartum: a preliminary study of amygdala function in postpartum depression
While contemporary diagnostic nosology characterizes postpartum depression (PPD) as a specifier of a major depressive disorder (MDD), this classification continues to be questioned. Functional magnetic resonance imaging (fMRI) holds the promise of helping to characterize the neuroanatomical dysfunction associated with dysregulated emotion after childbirth. Twenty postpartum women underwent fMRI in the presence of emotionally valenced stimuli. The observation of relative amygdala non-responsivity in subjects demonstrating greater depression symptomotology stands in contrast to imaging studies of MDD and provides insight into possible phenotypic differences of PPD.
Journal Article
Optimizing Imaging Protocols for Overweight and Obese Patients: A Lutetium Orthosilicate PET/CT Study
High photon attenuation and scatter in obese patients affect image quality. The purpose of the current study was to optimize lutetium orthosilicate (LSO) PET image acquisition protocols in patients weighing > or =91 kg (200 lb).
Twenty-five consecutive patients (16 male and 9 female) weighing > or =91 kg (200 lb; range, 91-168 kg [200-370 lb]) were studied with LSO PET/CT. After intravenous injection of 7.77 MBq (0.21 mCi) of 18F-FDG per kilogram of body weight, PET emission scans were acquired for 7 min/bed position. Single-minute frames were extracted from the 7 min/bed position scans to reconstruct 1-7 min/bed position scans for each patient. Three reviewers independently analyzed all 7 reconstructed whole-body images of each patient. A consensus reading followed in cases of disagreement. Thus, 175 whole-body scans (7 per patient) were analyzed for number of hypermetabolic lesions. A region-of-interest approach was used to obtain a quantitative estimate of image quality.
Fifty-nine hypermetabolic lesions identified on 7 min/bed position scans served as the reference standard. Interobserver concordance increased from 64% for 1 min/bed position scans to 70% for 3 min/bed position scans and 78% for 4 min/bed position scans. Concordance rates did not change for longer imaging durations. Region-of-interest analysis revealed that image noise decreased from 21% for 1 min/bed position scans to 14%, 13%, and 11% for, respectively, 4, 5, and 7 min/bed position scans. When compared with the reference standard, 14 lesions (24%) were missed on 1 min/bed position scans but only 2 (3%) on 4 min/bed position scans. Five minute/bed position scans were sufficient to detect all lesions identified on the 7 min/bed position scans.
Lesion detectability and reader concordance peaked for 5 min/bed position scans, with no further diagnostic gain achieved by lengthening the duration of PET emission scanning. Thus, 5 min/bed position scans are sufficient for optimal lesion detection with LSO PET/CT in obese patients.
Journal Article
Posterior cortical atrophy: an exemplar for renovating diagnostic formulation in neuropsychiatry
Neurodegenerative dementias represent among the most clinically and pathologically complex syndromes in neuropsychiatry. Phenomenologically protean, and often initially presenting with subtle subsyndromal characteristics, neurodegenerative behavioral syndromes can manifest with an assortment of cognitive, mood, personality, and comportmental changes, often alloyed with elementary neurologic (eg, motor) signs. A range of pathogenic mechanisms (eg, amyloid plaques, Pick bodies, etc) typically underlie corresponding clinical syndromes. However, overlap in both clinical expression and histopathologic comorbidities frequently exist among cortical and subcortical neurodegenerative disorders. Moreover, secondary central nervous system pathologies (eg, cerebrovascular disease) commonly coexist with neurodegenerative processes, further complicating clinical phenomenology-based nosologic categorization. Evolving insight into the etiologic mechanisms of neurodegenerative dementias, and correspondingly improving potential for intervention, require more precise differentiation among dementia subtypes and comprehensive identification of contemporaneous neurodegenerative processes. Increasing appreciation of this diagnostic complexity is prompting the need for renovation of existing diagnostic schemas. We address these issues by reviewing the atypical dementia type known as posterior cortical atrophy. We then use posterior cortical atrophy as an exemplar for renovating neuropsychiatric diagnostic classification to better account for the layered complexity of clinical and pathologic domains needing to be characterized to accurately and completely diagnose neuropsychiatric disturbances.
Journal Article
Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer’s disease
Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (
p
= 0.027) and independent (
p
= 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer’s disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer’s disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer’s markers.
Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.
Journal Article
A Dangerous Movie? Hollywood Does Psychoanalysis
After the appearance of David Cronenberg's film A Dangerous Method in 2011, dealing with the relationships of Sigmund Freud, C. G. Jung and Sabina Spielrein, Dr. Donald Ferrell published: A Dangerous Method, A Film Directed by David Cronenberg: An Extended Review (Ferrell 2012) in the Journal of Religion and Health. Upon its publication, Dr. Ferrell's article was nominated for a Gradiva Award by the National Association for the Advancement of Psychoanalysis. On November 1, 2013, the Association for the Psychoanalysis of Culture and Society held its annual conference at Rutgers University, New Brunswick, NJ. Dr. Billie Pivnick, a member at large of the Board of Directors of the APCS and also on the Editorial Board of the Journal of Religion and Health, persuaded the 2013 Conference Program Committee that Cronenberg's film would make an interesting subject for discussion for conference participants. To that end, Dr. Pivnick invited Dr. Ferrell, C. G. Jung Institute of New York, Dr. Steven Reisner, Coalition for an Ethical Psychology, and Dr. Martin Silverman, Training and Supervising Analyst and Supervising Child Analyst at the Institute for Psychoanalytic Education, NYU College of Medicine, Training and Supervising Analyst at the Center for Psychotherapy and Psychoanalysis of New Jersey, and Associate Editor of The Psychoanalytic Quarterly to serve as panel members to discuss: A Dangerous Movie? Hollywood does Psychoanalysis. Presentations on Cronenberg's film and the early history of psychoanalysis were given by Drs. Ferrell and Reisner, followed by a response to their presentations by Dr. Silverman. Dr. Pivnick chaired the session. The articles presented here were given originally at the APCS conference by Dr. Ferrell and Dr. Silverman. Dr. Reisner declined the invitation to submit his presentation for publication. Dr. Silverman's remarks were based not only on the presentation given by Dr. Ferrell at the session on A Dangerous Movie?, but also on his close and careful reading of the extended review of Cronenberg's film Dr. Ferrell published in the Journal of Religion and Health, as well as Dr. Reisner's presentation. It was appropriate for Dr. Silverman to serve in his capacity as discussant since he had earlier published a critical review of A Secret Symmetry. Sabina Spielrein Between Jung and Freud by Aldo Carotenuto (Silverman 1985).
Journal Article
Gram-Negative Sepsis and the Adult Respiratory Distress Syndrome
Gram-negative sepsis has dramatically increased in frequency throughout the twentieth century in the United States. Currently, ∼200,000 patients develop gram-negative sepsis each year in this country. Of these, about one-quarter develop the adult respiratory distress syndrome (ARDS). Among these critically ill patients, mortality is estimated at 60%–90%. In the complex series of events leading to acute lung injury in gram-negative sepsis, endotoxin is the proximal mediator. Although endotoxin may be capable of causing direct injury to the pulmonary endothelium, its primary role is as a trigger activating inflammatory agents, including complement, neutrophils, and platelets, and inducing the production of cytokines and arachidonic acid metabolites. The end results are impairment of the endothelial barrier, diffusely increased capillary permeability, and adherence of neutrophils to the endothelium with subsequent migration into the tissues. The consequent clinical syndrome is one of acute respiratory distress with pulmonary edema, poorly compliant lungs, and refractory hypoxemia. Endothelial injury often becomes widespread, leading to the failure of multiple organs, including the kidneys, brain, intestine, and liver. Conventional therapy consists of supplemental oxygen, positive end-expiratory pressure, inotropic agents, fluid management, and antibiotics aimed at the offending pathogen. Recent discoveries regarding the mediators of sepsis as well as the expansion of the biotechnological armamentarium have provided clinicians with a plethora of new tools with which to manipulate the host's inflammatory response. The challenge for the next decade will be to ensure the safety, efficacy, and cost-effective use of these expensive but potentially lifesaving immunomodulators, singly or in combination, as adjuvant therapy.
Journal Article
ERCP and stent therapy for progressive jaundice in hepatocellular carcinoma : which patients benefit, which patients don't?
Jaundice in hepatocellular carcinoma (HCC) can be due to biliary obstruction. Endoscopic retrograde cholangiopancreatography (ERCP) can be both diagnostic and therapeutic. Biliary stenting can relieve jaundice and allow further chemotherapy, but at additional expense and potential morbidity. We sought to determine whether CT scan or ultrasound (US) could identify which patients with HCC and jaundice would benefit from endoscopic stenting. We retrospectively analyzed 26 patients with HCC and jaundice who underwent ERCP after CT or US. We compared biliary dilation on CT or US with the dominant biliary stricture seen on ERCP, and with response to biliary stenting. Eleven of 26 patients had dominant biliary stricture on ERCP; 11 underwent stenting. Six of 11 (55%) stented patients had a significant decline in bilirubin; three became eligible for further chemotherapy. All six responders to stenting had biliary dilation on prior CT or US. Procedure-related complications occurred in 1/11 (9%) who underwent stent placement. In conclusion, in selected patients, stenting can safely relieve jaundice and allow subsequent chemotherapy. CT or US accurately predicted lesions that responded to stenting. ERCP and stenting provided no benefit in the absence of biliary dilation on CT or US.
Journal Article