Abstract Neurocognition and psychopathology are robust predictors of community functioning and relapse/rehospitalization in schizophrenia. Existing studies are however limited because they have ...ignored the most chronic, treatment-resistant patients. Moreover, the prediction of functional outcomes has yet to be extended to the duration of community tenure, an indicator of the capacity of chronically-hospitalized patients to gain traction in the community. The current study examined neurocognition and symptom severity at discharge as potential predictors of community tenure in chronically-hospitalized treatment-resistant patients. The study recruited 90 people with treatment-resistant schizophrenia who received services on an inpatient unit. Participants completed measures of psychopathology and neurocognition prior to discharge. Following discharge, participants were tracked at current residences six months and one year post-discharge to assess community tenure. The percentage of individuals who continued to live in the community at 12-month follow-up was 51%. Severe negative symptoms but not neurocognitive impairment or positive symptoms was a significant predictor of shorter post-hospital community tenure. Of the negative symptoms domain, anhedonia-asociality proved to be the most relevant predictor of community tenure in the sample. The capacity to elicit goal-directed behaviors in response to anticipated physical and social rewards may be an important treatment target for sustaining community tenure.
The immune and enteric nervous (ENS) systems monitor the frontier with commensal and pathogenic microbes in the colon. We investigated whether FoxP3+ regulatory T (Treg) cells functionally interact ...with the ENS. Indeed, microbe-responsive RORγ+ and Helios+ subsets localized in close apposition to nitrergic and peptidergic nerve fibers in the colon lamina propria (LP). Enteric neurons inhibited in vitro Treg (iTreg) differentiation in a cell-contact-independent manner. A screen of neuron-secreted factors revealed a role for interleukin-6 (IL-6) in modulating iTreg formation and their RORγ+ proportion. Colonization of germfree mice with commensals, especially RORγ+ Treg inducers, broadly diminished colon neuronal density. Closing the triangle, conditional ablation of IL-6 in neurons increased total Treg cells but decreased the RORγ+ subset, as did depletion of two ENS neurotransmitters. Our findings suggest a regulatory circuit wherein microbial signals condition neuronal density and activation, thus tuning Treg cell generation and immunological tolerance in the gut.
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•Treg cells in the colon lamina propria reside close to neuron projections•Neurons modulate the differentiation and phenotype of iTreg cells in culture via IL-6•Neuron-specific ablation of Il6 increases the number of RORγ+ Treg cells in vivo•Microbial colonization affects a subset of neurons in the enteric nervous system
Regulatory T (Treg) cells lie in proximity to nerve fibers in the colon lamina propria. Yan et al. reveal a regulatory circuit wherein microbial signals condition neuronal density and activation, which in turn, via neuron-produced IL-6, tunes Treg cell generation, which has implications for intestinal tolerance.
V(D)J recombination generates mature B cells that express huge repertoires of primary antibodies as diverse immunoglobulin (Ig) heavy chain (IgH) and light chain (IgL) of their B cell antigen ...receptors (BCRs). Cognate antigen binding to BCR variable region domains activates B cells into the germinal center (GC) reaction in which somatic hypermutation (SHM) modifies primary variable region-encoding sequences, with subsequent selection for mutations that improve antigen-binding affinity, ultimately leading to antibody affinity maturation. Based on these principles, we developed a humanized mouse model approach to diversify an anti-PD1 therapeutic antibody and allow isolation of variants with novel properties. In this approach, component Ig gene segments of the anti-PD1 antibody underwent de novo V(D)J recombination to diversify the anti-PD1 antibody in the primary antibody repertoire in the mouse models. Immunization of these mouse models further modified the anti-PD1 antibodies through SHM. Known anti-PD1 antibodies block interaction of PD1 with its ligands to alleviate PD1-mediated T cell suppression, thereby boosting antitumor T cell responses. By diversifying one such anti-PD1 antibody, we derived many anti-PD1 antibodies, including anti-PD1 antibodies with the opposite activity of enhancing PD1/ligand interaction. Such antibodies theoretically might suppress deleterious T cell activities in autoimmune diseases. The approach we describe should be generally applicable for diversifying other therapeutic antibodies.
Abstract Lumbar disc herniations (LDH) may regress with conservative management; however, this phenomenon is poorly understood for the sequestrated subtype of LDH. We present one of the first ...comprehensive literature reviews specifically addressing the spontaneous regression of sequestrated intervertebral discs. We reviewed all publications with lumbar disc herniations, sequestrated subtype. Our results were then narrowed to patients who experienced spontaneous regression of the sequestration. Based on our literature review of 53 cases, patients with sequestrated lumbar disc herniations experienced symptomatic resolution in a mean of 1.33 ± 1.34 months and radiographic resolution in 9.27 ± 13.32 months. Symptomatic patients with sequestrated discs present similarly to those with other types of lumbar disc herniations. Sequestrations may have the highest likelihood to radiographically regress in the shortest time frame in comparison to the remaining subtypes of LDH. The most likely mechanism for regression is an inflammatory response elicited against the free fragment. Patients with disc sequestrations may be managed conservatively, in the absence of intractable pain, inability to walk, weakness or symptoms suggestive of cauda equina syndrome.
HIV-1 vaccine development aims to elicit broadly neutralizing antibodies (bnAbs) against diverse viral strains. In some HIV-1–infected individuals, bnAbs evolved from precursor antibodies through ...affinity maturation. To induce bnAbs, a vaccine must mediate a similar antibody maturation process. One way to test a vaccine is to immunize mouse models that express human bnAb precursors and assess whether the vaccine can convert precursor antibodies into bnAbs. A major problem with such mouse models is that bnAb expression often hinders B cell development. Such developmental blocks may be attributed to the unusual properties of bnAb variable regions, such as poly-reactivity and long antigen-binding loops, which are usually under negative selection during primary B cell development. To address this problem, we devised a method to circumvent such B cell developmental blocks by expressing bnAbs conditionally in mature B cells. We validated this method by expressing the unmutated common ancestor (UCA) of the human VRC26 bnAb in transgenic mice. Constitutive expression of the VRC26UCA led to developmental arrest of B cell progenitors in bone marrow; poly-reactivity of the VRC26UCA and poor pairing of the VRC26UCA heavy chain with the mouse surrogate light chain may contribute to this phenotype. The conditional expression strategy bypassed the impediment to VRC26UCA B cell development, enabling the expression of VRC26UCA in mature B cells. This approach should be generally applicable for expressing other bnAbs that are under negative selection during B cell development.
BACKGROUND:Adjacent segment disease (ASD) has not been described after laminectomy without fusion.
OBJECTIVE:To determine the incidence of ASD after a 1- or 2-level lumbar laminectomy.
METHODS:We ...retrospectively reviewed medical records of all patients who underwent 1- or 2-level, bilateral lumbar laminectomy without fusion for degenerative spinal disease (all follow-up ≥1 year). ASD was defined as clinical and/or radiographic evidence of degenerative spinal disease that required reoperation at the level above or below the index laminectomy.
RESULTS:Of the 398 patients, the incidence of ASD requiring reoperation was 10%. The 39 ASD cases were almost equally distributed at L2-L3 (31%), L3-L4 (26%), and L5-S1 (31%), and to a lesser extent at L4-L5 (15%) (P = .51). The ASD incidences of 10% and 9% were equivalent after a 1- and 2-level laminectomy, respectively (P = .76). Rostral ASD was statistically more common than caudal ASD after both the 1- (P < .001) and 2- (P < .001) level laminectomy. Of the 39 ASD cases, 95% required laminectomy, 26% discectomy, and 49% fusion. Average time to ASD was 4 years. After a Kaplan-Meier analysis, time to reoperation for ASD was equivalent among the 1- and 2-level laminectomy cohorts (log-rank test, P = .13).
CONCLUSION:The cumulative incidence of ASD requiring reoperation was 10% over a mean of 4 years. Both the 1- and 2-level laminectomy cohorts experienced equivalent incidences and rates of ASD. Of the 39 operations for ASD, about half required a fusion.
ABBREVIATIONS:ASD, adjacent segment diseaseIR, incident rates
BACKGROUND:The safety and efficacy of spinal fusion in the elderly population remains uncertain with conflicting data.
OBJECTIVE:To determine if elderly patients undergoing instrumented lumbar fusion ...have increased 30-day complication rates compared to younger patients.
METHODS:The American College of Surgeons National Surgical Quality Improvement Program was used to identify all patients undergoing instrumented posterolateral lumbar fusion between 2005 and 2011. Patients were stratified by decade cohorts as follows<65, 65 to 75, 75 to 85, and ≥85 years old. All 30-day complications were grouped as overall composite morbidity and were compared using multivariate analysis.
RESULTS:A total of 1395 patients were identified and the overall 30-day complication rate was 11.47%. The complication rates were 9.04% and 14.05% for patients younger than 65 and older than 65, respectively. When stratified by decade cohorts, the complication rates were 9.04% for the <65 cohort, 13.46% for the 65 to 75 cohort, 16.17% for the >75 to 85 cohort, and 4.00% for the ≥85 cohort. Multivariable regression analysis revealed no statistically significant difference between the <65 and ≥65 age cohorts (odds ratio = 1.26; 95% confidence interval0.87-2.19). After stratifying into age cohorts, multivariable analyses revealed no difference in odds of postoperative complication occurrence for any age cohort when compared with the referent group (<65 years of age).
CONCLUSION:Patients older than 65 years of age have significantly higher rates of complications after lumbar fusion when compared to younger patients. However, multivariable analysis revealed that age was not an independent risk factor for complication occurrence after lumbar fusion.
ABBREVIATIONS:NSQIP, National Surgical Quality Improvement ProgramPLF, posterolateral fusions
Rationale
We believe that this study represents an innovative approach to clarifying the definitions of routine, empathic and compassionate health care, as well as of sympathy. We emphasize the ...importance of affective empathy and its intensification in the context of patient suffering (compassion), without abandoning the ideal of clinical equanimity.
Methods
We develop a pedagogical model for clinicians and trainees who are weaker in their empathic skills that includes four levels of growth. We clarify representative obstacles to empathic and compassionate care in education and clinical practice. We summarize the four beneficiaries of empathic and compassionate care (clinicians, patients, trainees, institutions). We suggest areas for future research, including the development of a compassion scale and conclude with a statement on how the conceptual and professional confusion we address adversely impacts patients and trainees. The article represents the consensus work of a group of health care professionals and students at Stony Brook University Hospital and School of Medicine who have been engaged in this project for several years through the Center for Medical Humanities, Compassionate Care, and Bioethics, established in August of 2008.
Conclusions
We discern a shift away from concepts of clinical empathy and compassionate care that deny a significant place for an affective component and that idealize ‘detachment’.
Abstract
BACKGROUND:
The safety and efficacy of spinal fusion in the elderly population remains uncertain with conflicting data.
OBJECTIVE:
To determine if elderly patients undergoing instrumented ...lumbar fusion have increased 30-day complication rates compared to younger patients.
METHODS:
The American College of Surgeons National Surgical Quality Improvement Program was used to identify all patients undergoing instrumented posterolateral lumbar fusion between 2005 and 2011. Patients were stratified by decade cohorts as follows: <65, 65 to 75, 75 to 85, and ≥85 years old. All 30-day complications were grouped as overall composite morbidity and were compared using multivariate analysis.
RESULTS:
A total of 1395 patients were identified and the overall 30-day complication rate was 11.47%. The complication rates were 9.04% and 14.05% for patients younger than 65 and older than 65, respectively. When stratified by decade cohorts, the complication rates were 9.04% for the <65 cohort, 13.46% for the 65 to 75 cohort, 16.17% for the >75 to 85 cohort, and 4.00% for the ≥85 cohort. Multivariable regression analysis revealed no statistically significant difference between the <65 and ≥65 age cohorts (odds ratio = 1.26; 95% confidence interval: 0.87-2.19). After stratifying into age cohorts, multivariable analyses revealed no difference in odds of postoperative complication occurrence for any age cohort when compared with the referent group (<65 years of age).
CONCLUSION:
Patients older than 65 years of age have significantly higher rates of complications after lumbar fusion when compared to younger patients. However, multivariable analysis revealed that age was not an independent risk factor for complication occurrence after lumbar fusion.
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