Recent Modifications of the Nuss Procedure: The Pursuit of Safety During the Minimally Invasive Repair of Pectus Excavatum.

OBJECTIVE: To review standardized Nuss correction of pectus excavatum and vacuum bell treatment over the last 10 years. SUMMARY OF BACKGROUND DATA: In 2010, we reported 21 years of the Nuss procedure in 1215 patients. METHODS: Over the last 10 years, 2008-2018, we evaluated 1885 pectus excavatum patients. Surgery was indicated for well-defined objective criteria. A consistent operation was performed by 8 surgeons in 1034 patients, median 15 years, (range 6-46); 996 were primary, and 38 redo operations. Surgical patients' mean computed tomography index was 5.46. Mitral valve prolapse was present in 5.4%, Marfan syndrome in 1.1% and scoliosis in 29%. Vacuum bell treatment was introduced for 218 patients who did not meet surgical criteria or were averse to surgery. RESULTS: At primary operation, 1 bar was placed in 49.8%; 2 bars, 49.4%; and 3 bars, 0.7%. There were no deaths. Cardiac perforation occurred in 1 patient who had undergone previous cardiac surgery. Paraplegia after epidural catheter occurred once. Reoperation for bar displacement occurred in 1.8%, hemothorax in 0.3%, and wound infection in 2.9%; 1.4% required surgical drainage. Allergy to stainless steel was identified in 13.7%. A good anatomic outcome was always achieved at bar removal. Recurrence requiring reoperation occurred in 3 primary surgical patients. Two patients developed carinate overcorrection requiring reoperation. Vacuum bell treatment produced better results in younger and less severe cases. CONCLUSIONS: A standardized Nuss procedure was performed by multiple surgeons in 1034 patients with good overall safety and results in primary repairs. Vacuum bell treatment is useful.

Juvenile dermatomyositis resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination of cyclophosphamide and rituximab: case-based review.

Dermatomyositis (DM) is a multi-system disease that results in chronic inflammation principally of the skin and striated muscle. Small blood vessel injury in the GI tract has been described in dermatomyositis, manifesting as bleeding, ulceration, pneumatosis intestinalis, and ultimately perforation. Recent histopathological studies have shown deposits in the capillaries of the skin, gastrointestinal tract, and brain of patients with dermatomyositis similar to that found in patients with Degos disease, suggesting these disease processes are closely related or represent varying degrees of severity on the same pathologic spectrum. We report a case of juvenile dermatomyositis (JDM) resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination rituximab and cyclophosphamide therapy. We systematically reviewed the literature detailing the medical and surgical treatments for gastrointestinal perforation in dermatomyositis, Degos-like dermatomyositis, and Degos disease. In addition to our case, as of October 2019, we identified 36 cases describing gastrointestinal perforation in patients with underlying dermatomyositis, 5 cases of Degos-like dermatomyositis and 17 cases of idiopathic Degos disease. Corticosteroid therapy was used widely for dermatomyositis and Degos-like dermatomyositis, while antiplatelet and anticoagulant medications were chiefly used for patients with idiopathic Degos disease. However, there were no cases that detailed the successful treatment of dermatomyositis or Degos disease with gastrointestinal perforation with rituximab alone or combined with cyclophosphamide. We report that rituximab, in combination with cyclophosphamide, can be used as a novel adjunctive therapy to successfully treat dermatomyositis with Degos-like gastrointestinal perforation.

Omission of temporal nuisance regressors from dual regression can improve accuracy of fMRI functional connectivity maps.

Functional connectivity (FC) maps from brain fMRI data can be derived with dual regression, a proposed alternative to traditional seed-based FC (SFC) methods that detect temporal correlation between a predefined region (seed) and other regions in the brain. As with SFC, incorporating nuisance regressors (NR) into the dual regression must be done carefully, to prevent potential bias and insensitivity of FC estimates. Here, we explore the potentially untoward effects on dual regression that may occur when NR correlate highly with the signal of interest, using both synthetic and real fMRI data to elucidate mechanisms responsible for loss of accuracy in FC maps. Our tests suggest significantly improved accuracy in FC maps derived with dual regression when highly correlated temporal NR were omitted. Single-map dual regression, a simplified form of dual regression that uses neither spatial nor temporal NR, offers a viable alternative whose FC maps may be more easily interpreted, and in some cases be more accurate than those derived with standard dual regression.

Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression.

OBJECTIVE: This study tests the hypothesis that the use of semantic organizational strategy during the free-recall phase of a verbal memory task predicts remission of geriatric depression. METHODS: Sixty-five older patients with major depression participated in a 12-week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2-week drug washout period. The Hopkins Verbal Learning Test-Revised was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7 for 2 consecutive weeks and no longer meeting the DSM-IV-TR criteria for major depression. The association between the number of clusters used at the final learning trial (trial 3) and remission was examined using Cox's proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and the number of words recalled after a 25-min delay was examined in a regression with age and education as covariates. RESULTS: Higher number of clusters utilized predicted remission rates (hazard ratio, 1.26 (95% confidence interval, 1.04-1.54); χ(2) = 4.23, df = 3, p = 0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58) = 7.93; p < 0.001). CONCLUSIONS: Effective semantic strategy use at baseline on a verbal list learning task by older depressed patients was associated with higher rates of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response.

The First Year of the Psychiatric Diseases Section.

Since its inception in May 2021, the Psychiatric Diseases Section of Brain Sciences has grown to include a staff of 28 academic editors with expertise related to clinical psychiatry, in addition to its supporting staff of managing and English-language editors [...].

What Do These Findings Tell Us? Comment on Tinella et al. Cognitive Efficiency and Fitness-to-Drive along the Lifespan: The Mediation Effect of Visuospatial Transformations. Brain Sci. 2021, 11, 1028.

Tinella et al.'s recent article [...].

Replicability in Brain Imaging.

In the early 2010s, the "replication crisis" and synonymous terms ("replicability crisis" and "reproducibility crisis") were coined to describe growing concerns regarding published research results too often not being replicable, potentially undermining scientific progress [...].

Seed-based dual regression: An illustration of the impact of dual regression's inherent filtering of global signal.

BACKGROUND: Functional connectivity (FC) maps from brain fMRI data are often derived with seed-based methods that estimate temporal correlations between the time course in a predefined region (seed) and other brain regions (SCA, seed-based correlation analysis). Standard dual regression, which uses a set of spatial regressor maps, can detect FC with entire brain "networks," such as the default mode network, but may not be feasible when detecting FC associated with a single small brain region alone (for example, the amygdala). NEW METHOD: We explored seed-based dual regression (SDR) from theoretical and practical points of view. SDR is a modified implementation of dual regression where the set of spatial regressors is replaced by a single binary spatial map of the seed region. RESULTS: SDR allowed detection of FC with small brain regions. COMPARISON WITH EXISTING METHOD: For both synthetic and natural fMRI data, detection of FC with SDR was identical to that obtained with SCA after removal of global signal from fMRI data with global signal regression (GSR). In the absence of GSR, detection of FC was significantly improved when using SDR compared with SCA. CONCLUSION: The improved FC detection achieved with SDR was related to a partial filtering of the global signal that occurred during spatial regression, an integral part of dual regression. This filtering can sometimes lead to spurious negative correlations that result in a widespread negative bias in FC derived with any application of dual regression. We provide guidelines for how to identify and correct this potential problem.

Increasing severity of pectus excavatum is associated with reduced pulmonary function.

OBJECTIVE: To determine whether pulmonary function decreases as a function of severity of pectus excavatum, and whether reduced function is restrictive or obstructive in nature in a large multicenter study. STUDY DESIGN: We evaluated preoperative spirometry data in 310 patients and lung volumes in 218 patients aged 6 to 21 years at 11 North American centers. We modeled the impact of the severity of deformity (based on the Haller index) on pulmonary function. RESULTS: The percentages of patients with abnormal forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced expiratory flow from 25% exhalation to 75% exhalation, and total lung capacity findings increased with increasing Haller index score. Less than 2% of patients demonstrated an obstructive pattern (FEV(1)/FVC <67%), and 14.5% demonstrated a restrictive pattern (FVC and FEV(1) <80% predicted; FEV(1)/FVC >80%). Patients with a Haller index of 7 are >4 times more likely to have an FVC of ≤80% than those with a Haller index of 4, and are also 4 times more likely to exhibit a restrictive pulmonary pattern. CONCLUSIONS: Among patients presenting for surgical repair of pectus excavatum, those with more severe deformities have a much higher likelihood of decreased pulmonary function with a restrictive pulmonary pattern.

Executive function and short-term remission of geriatric depression: the role of semantic strategy.

BACKGROUND: This study tested the hypothesis that use of semantic organizational strategy in approaching the Mattis Dementia Rating Scale (MDRS) complex verbal initiation/perseveration (CV I/P) task, a test of semantic fluency, is the function specifically associated with remission of late-life depression. METHOD: Seventy elders with major depression participated in a 12-week escitalopram treatment trial. Neuropsychologic performance was assessed at baseline after a 2-week drug washout period. Patients with a Hamilton Depression Rating Scale Score ≤7 for 2 consecutive weeks and who no longer met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were considered to be remitted. Cox's proportional hazards survival analysis was used to examine the relationship between subtests of the I/P, other neuropsychologic domains, and remission rate. Participants' performance on the CV I/P subscale was coded for perseverations, and use of semantic strategy. RESULTS: The relationship between the performance on the CV I/P subscale and remission rate was significant. No other subtest of the MDRS I/P evidenced this association. There was no significant relationship between speed, confrontation naming, verbal memory, or perseveration with remission rate. Remitters' use of verbal strategy was significantly greater than nonremitters. CONCLUSIONS: Geriatric depressed patients who showed decrements in performance on a semantic fluency task showed poorer remission rates than those who showed adequate performance on this measure. Executive impairment in verbal strategy explained performance. This finding supports the concept that executive functioning exerts a "top down" effect on other basic cognitive processes, perhaps as a result of frontostriatal network dysfunction implicated in geriatric depression.

Hippocampal volumes and the brain-derived neurotrophic factor val66met polymorphism in geriatric major depression.

OBJECTIVES: structural abnormalities in the hippocampus have been implicated in the pathophysiology of major depressive disorder (MDD). The brain-derived neurotrophic factor (BDNF) val66met polymorphism may contribute to these abnormalities and therefore confer vulnerability to MDD. This study examined whether there is a relationship among BDNF genotype, hippocampal volumes, and MDD in older adults. METHODS: thirty-three older adults with MDD and 23 psychiatrically normal comparison subjects were studied. Structural magnetic resonance imaging analysis was used to quantify hippocampal volumes. A repeated-measures analysis of covariance examined the relationships among BDNF val66met (val/val, met carrier), diagnosis (depressed, nondepressed), and hippocampal volumes (right, left). Age, gender, education, and whole brain volume were included as covariates. RESULTS: elderly MDD BDNF val/val homozygotes had significantly higher right hippocampal volumes compared with nondepressed val/val subjects. However, there was no difference between the depressed and healthy nondepressed met carriers. In addition, depressed met carriers had an earlier age of onset of depressive illness than val/val homozygotes, but age of onset did not moderate the relationship between hippocampal volumes and MDD diagnosis. CONCLUSION: these results provide preliminary evidence of a neuroprotective role of the val/val genotype, suggesting that neurotrophic factor production protects against pathophysiological processes triggered by depression in older adults with later age of onset of MDD. The BDNF val66met polymorphism may play a salient role in structural alterations of the hippocampus in older adults with MDD.

The Quest for Psychiatric Advancement through Theory, beyond Serendipity.

Over the past century, advancements in psychiatric treatments have freed countless individuals from the burden of life-long, incapacitating mental illness. These treatments have largely been discovered by chance. Theory has driven advancement in the natural sciences and other branches of medicine, but psychiatry remains a field in its "infancy". The targets for healing in psychiatry lie within the realm of the mind's subjective experience and thought, which we cannot yet describe in terms of their biological underpinnings in the brain. Our technology is sufficiently advanced to study brain neurons and their interactions on an electrophysiological and molecular level, but we cannot say how these form a single feeling or thought. While psychiatry waits for its "Copernican Revolution", we continue the work in developing theories and associated experiments based on our existing diagnostic systems, for example, the Diagnostic and Statistical Manual of Mental Disorders (DSM), International Classification of Diseases (ICD), or the more newly introduced Research Domain Criteria (RDoC) framework. Understanding the subjective reality of the mind in biological terms would doubtless lead to huge advances in psychiatry, as well as to ethical dilemmas, from which we are spared for the time being.

Selective use of sternal elevation before substernal dissection in more than 2000 Nuss repairs at a single institution.

BACKGROUND/PURPOSE: Evaluate the safety of sternal elevation (SE) used selectively before creating the substernal tunnel during the Nuss procedure. METHODS: An IRB-approved (01-05-EX-0175-HOSP), single institution, retrospective review was performed (1/1/1997-11/20/2017). Primary and secondary Nuss repairs (i.e., previous Nuss, Ravitch, thoracotomy, or sternotomy) are included. SE use, cardiac injuries, and pectus bar infections are reported. Chi square and Fisher's exact test (FE) were used (critical p < .05). RESULTS: 2037 patients [(80% male; mean age 15.2 years (SD = 4.4, range 3-46); mean Haller index (HI) 5.3 (SD = 5.7, range 1.73-201)] underwent Nuss repair. SE was used before creating the substernal tunnel in 171 (8.4%): 160 (8.2%) of 1949 primary and 11 (12.5%) of 88 secondary repairs. SE use increased significantly [χ2(2) = 118.93; p < .001] over time and with increasing HI [χ2(3) = 59.9; p < .001]. No cardiac injuries occurred in primary repairs but two occurred in patients with previous sternotomy. Infection rates were not different with (2.9%) or without SE (1.8%) [χ2(1) =1.14; p = .285] and not higher with off-label VB (1.5%) versus other SE techniques (3.8%) [FE, p = .65)]. CONCLUSION: Selective use of sternal elevation before substernal dissection during the Nuss procedure is safe but may not prevent cardiac injuries in patients with previous sternotomy. Infection rates were not increased with SE. TYPE OF STUDY: Retrospective review. LEVEL OF EVIDENCE: IV.

Twenty-one years of experience with minimally invasive repair of pectus excavatum by the Nuss procedure in 1215 patients.

OBJECTIVE: To review the technical improvements and changes in management that have occurred over 21 years, which have made the minimally invasive repair of pectus excavatum safer and more successful. SUMMARY BACKGROUND DATA: In 1997, we reported our 10-year experience with a new minimally invasive technique for surgical correction of pectus excavatum in 42 children. Since then, we have treated an additional 1173 patients, and in this report, we summarize the technical modifications which have made the repair safer and more successful. METHODS: From January 1987 to December 2008, we evaluated 2378 pectus excavatum patients. We established criteria for surgical intervention, and patients with a clinically and objectively severe deformity were offered surgical correction. The objective criteria used for surgical correction included computed tomography (CT) scans of the chest, resting pulmonary function studies (spirometry and/or plethysmography), and a cardiology evaluation which included echocardiogram and electrocardiogram. Surgery was indicated if the patients were symptomatic, had a severe pectus excavatum on a clinical basis and fulfilled two or more of the following: CT index greater than 3.25, evidence of cardiac or pulmonary compression on CT or echocardiogram, mitral valve prolapse, arrhythmia, or restrictive lung disease. Data regarding evaluation, treatment, and follow up have been prospectively recorded since 1994. Surgical repair was performed in 1215 (51%) of 2378 patients evaluated. Of these, 1123 were primary repairs, and 92 were redo operations. Bars have been removed from 854 patients; 790 after primary repair operations, and 64 after redo operations. RESULTS: The mean Haller CT index was 5.15 ± 2.32 (mean ± SD). Pulmonary function studies performed in 739 patients showed that FVC, FEV1, and FEF25-75 values were decreased by a mean of 15% below predicted value. Mitral valve prolapse was present in 18% (216) of 1215 patients and arrhythmias in 16% (194). Of patients who underwent surgery, 2.8% (35 patients) had genetically confirmed Marfan syndrome and an additional 17.8% (232 patients) had physical features suggestive of Marfan syndrome. Scoliosis was noted in 28% (340). At primary operation, 1 bar was placed in 69% (775 patients), 2 bars in 30% (338), and 3 bars in 0.4% (4). Complications decreased markedly over 21 years. In primary operation patients, the bar displacement rate requiring surgical repositioning decreased from 12% in the first decade to 1% in the second decade. Allergy to nickel was identified in 2.8% (35 patients) of whom 22 identified preoperatively received a titanium bar, 10 patients were treated successfully with prednisone and 3 required bar removal: 2 were switched to a titanium bar, and 1 required no further treatment. Wound infection occurred in 1.4% (17 patients), of whom 4 required surgical drainage (0.4% of the total). Hemothorax occurred in 0.6% (8 patients); 4 during the postoperative period and four occurred late. Postoperative pulmonary function testing has shown significant improvement. A good or excellent anatomic surgical outcome was achieved in 95.8% of patients at the time of bar removal. A fair result occurred in 1.4%, poor in 0.8%, and recurrence of sufficient severity to require reoperation occurred in 11 primary surgical patients (1.4%). Five patients (0.6%) had their bars removed elsewhere. In the 752 patients, more than 1 year post bar removal, the mean time from initial operation to last follow up was 1341 ± 28 days (SEM), and time from bar removal to last follow-up is 854 ± 51 days. Age at operation has shifted from a median age of 6 years (range 1-15) in the original report to 14 years (range 1-31). The minimally invasive procedure has been successfully performed in 253 adult patients aged 18 to 31 years of age. CONCLUSIONS: The minimally invasive repair of pectus excavatum has been performed safely and effectively in 1215 patients with a 95.8% good to excellent anatomic result in the primary repairs at our institution.

Indications and technique of Nuss procedure for pectus excavatum.

Pectus excavatum most frequently involves the lower sternum and chest wall. Because the morphology varies, preoperative imaging for anatomic assessment and documentation of dimensions of the chest are important. Many modifications have been made to the minimally invasive procedure since it was first performed in 1987. As a result, there has been an increase in the number of patients seeking surgical correction. This article discusses the clinical features of pectus excavatum and reviews the preoperative considerations and the steps involved in the repair of the deformity.

Prevalence of pectus excavatum in an adult population-based cohort estimated from radiographic indices of chest wall shape.

BACKGROUND: Pectus excavatum is the most common chest wall skeletal deformity. Although commonly evaluated in adolescence, its prevalence in adults is unknown. METHODS AND FINDINGS: Radiographic indices of chest wall shape were analyzed for participants of the first (n = 2687) and second (n = 1780) phases of the population-based Dallas Heart Study and compared to clinical cases of pectus (n = 297). Thoracic computed tomography imaging studies were examined to calculate the Haller index, a measure of thoracic axial shape, and the Correction index, which quantitates the posterior displacement of the sternum relative to the ribs. At the level of the superior xiphoid, 0.5%, 5% and 0.4% of adult Dallas Heart Study subjects have evidence of pectus excavatum using thresholds of Haller index >3.25, Correction index >10%, or both, respectively. Radiographic measures of pectus are more common in females than males and there is a greater prevalence of pectus in women than men. In the general population, the Haller and Correction indices are associated with height and weight, independent of age, gender, and ethnicity. Repeat imaging of a subset of subjects (n = 992) demonstrated decreases in the mean Haller and Correction indices over seven years, suggesting change to a more circular axial thorax, with less sternal depression, over time. CONCLUSIONS: To our knowledge, this is the first study estimating the prevalence of pectus in an unselected adult population. Despite the higher reported prevalence of pectus cases in adolescent boys, this study demonstrates a higher prevalence of radiographic indices of pectus in adult females.

Development and validation of the Pectus Carinatum Body Image Quality of Life (PeCBI-QOL) questionnaire.

INTRODUCTION: While body image disturbances and quality of life in persons with pectus excavatum (PE) have been well documented, very little has been done to systematically measure and document the same in patients with pectus carinatum (PC). Because of this, the current study aimed to develop and validate an instrument to assess body image related quality of life in patients with PC and their parents. METHOD: Participants: Two waves of data collection took place. The development phase enrolled 78 PC patients and 76 matched parents. The validation phase enrolled 50 PC patients and 50 parents. Mean age at the initiation of treatment was 15.14 (SD = 2.54). Participants were mostly boys (85.9%) and White or Caucasian (89.7%). Instrument development, refinement, and validation: A group of 5 experts in chest wall deformities used existing measures of body image disturbances in PE, combined with the broader body image literature, to develop larger item pools for patients and their parents. Item analysis from this phase was used to remove poorly performing or statistically redundant items. In the validation phase, refined patient and parent instruments were examined using exploratory principal components factor analysis (EFA) with parallel analysis for factor retention, followed by Varimax rotation to identify a final factor solution. RESULTS/DISCUSSION: This development and refinement process yielded a final questionnaire for patients (18 items) and parents (15 items). The patient questionnaire includes four subscales, each with good internal consistency: Body Image Disturbance; Treatment Motivation/Engagement; Physical Limitations; and Social Disadvantage. The parent questionnaire includes 3 subscales: Body Image Disturbance; Treatment Motivation/Engagement; Physical Limitations. Patient and parent scales showed moderate correlations. Among patients with measures pre- and posttreatment, there was a significant improvement in overall PeCBI-QOL score. We demonstrate, in this study, that body image and related quality of life can be reliably and validly assessed with the PeCBI-QOL, which has implications for more comprehensively documenting the negative psychological and functional consequences of pectus carinatum. TYPE OF STUDY/LEVEL OF EVIDENCE: Study of diagnostic test/III.

Pectus excavatum: historical background, clinical picture, preoperative evaluation and criteria for operation.

Pectus excavatum is a depression of the sternum and costal cartilages which may present at birth, or more commonly during the teenage growth spurt. Symptoms of lack of endurance, shortness of breath with exercise, or chest pain are frequent. Although pectus excavatum may be a component of some uncommon syndromes, patients usually are healthy. Evaluation should include careful anatomic description with photographs, radiography to demonstrate the depth of the depression, extent of cardiac compression, or displacement, measurement of pulmonary function, and echocardiography to look for mitral valve prolapse (in 15%) or diminished right ventricular volume. Indications for surgical treatment include two or more of the following: a severe, symptomatic deformity; progression of deformity; paradoxical respiratory chest wall motion; computer tomography scan with a pectus index greater than 3.25; cardiac compression/displacement and/or pulmonary compression; pulmonary function studies showing restrictive disease; mitral valve prolapse, bundle branch block, or other cardiac pathology secondary to compression of the heart; or failed previous repair(s). The developmental factors, genetics, and physiologic abnormalities associated with the condition are reviewed.

Minimally invasive surgical correction of chest wall deformities in children (Nuss procedure).

Pectus excavatum can be corrected with minimally invasive techniques that do not require costal cartilage resection or sternal osteotomy. At our institution, 947 patients have been safely and effectively managed with excellent long-term results and low morbidity.

Outcomes, quality of life, and long-term results after pectus repair from around the globe.

The procedure introduced by Donald Nuss in 1997 at the American Pediatric Surgical Association meeting has now been adopted by pediatric, thoracic, and plastic surgeons around the globe. Since its introduction, the Nuss procedure has been the subject of intense scrutiny. More than 20 years since the original publication, medical centers from around the world have reported their experience with the procedure and robust evidence now supports its safety and efficacy. Additionally, in collaboration with psychologists in Norfolk, a methodology was devised to measure the psychosocial as well as the physical benefits of the procedure. Extensive independent multinational and multi-institutional data demonstrate repair of pectus excavatum using the Nuss procedure results in marked improvement in both physical function and body image. This report reviews the outcomes, quality of life, and long-term results of numerous centers worldwide since the introduction of the procedure.