Optimization and Standardization of the Immunodeficient Mouse Model for Assessing Fat Grafting Outcomes.

BACKGROUND: Animal models are often used to assess interventions that might improve fat grafting outcomes; however, there is great variability in the models. The authors sought to determine the predictive value of the immunocompromised mouse model for fat grafting so that experiments could be standardized and optimized. METHODS: Human lipoaspirate injections at different volumes and time points were assessed in a nude mouse model and compared with control injections of nonviable fat. Volume retention and explant histologic score were compared. In a separate study, interanimal reproducibility was determined by implanting a highly consistent hydrogel and measuring variability in volume retention. RESULTS: Injection volume significantly affects adipose resorption kinetics at 6 and 12 weeks. Masson trichrome staining revealed that macrophages were unable to infiltrate large (1 ml) grafts, and oil cysts were not absorbed by 18 weeks, which interfered with interpretation of volume retention data. Nonviable tissue was resorbed when grafts were 0.3 ml, and quantification of graft histologic viability correlated well with graft retention at all study time points. Interanimal variability was measured to be 8.44 percent of the mean retention volume for small graft volumes. CONCLUSIONS: Human fat graft retention in the immunodeficient mouse correlates with graft viability in small, 0.3-ml-volume grafts. However, centralized oil cysts in nonviable 1.0-ml grafts were not resorbed by 18 weeks and thus volume measurements were confounded and not significantly different from viable samples. In addition, tissue injury scores increased in initially healthy fat grafts at 18 weeks, possibly because of a delayed immune reaction.

Utilization of Flow Cytometry in Pediatric Fine-Needle Aspiration Biopsy Specimens.

BACKGROUND: Fine-needle aspiration (FNA) coupled with flow cytometry (FC) can be helpful in suspicious pediatric lymph nodes or masses to exclude a lymphoproliferative disorder. The aim of this study was to analyze FC findings in a series of pediatric FNAs and to correlate abnormal findings with follow-up information. MATERIALS AND METHODS: All pediatric FNAs performed at a tertiary-care children's hospital over a 46-month period that had FC performed were retrospectively analyzed and correlated with follow-up. RESULTS: A total of 163 FNA procedures were performed in children (age ≤21 years), and 47 (28.8%) of these cases had FC performed. Specimens were mostly obtained from the head and neck (72.3% of cases). Nine cases (19.1%) had abnormal FC findings, including double-negative T cells (n = 3; 33.3%), double-positive T cells (n = 3; 33.3%), excess λ light chains (n = 1; 11.1%), weak CD34 positivity (n = 1; 11.1%), and T-lymphoblastic lymphoma (n = 1; 11.1%). CONCLUSION: Unusual FC results that are not diagnostic of malignancy can be seen in lymph node FNA in a minority of young patients. In our series, these findings were seen mainly in small populations of T cells and occurred primarily in the setting of reactive lymphoid hyperplasia or ectopic thymic tissue. Cytopathologists performing FNA on children should be aware of these abnormalities and, although they may warrant further investigation and follow-up, they are unlikely to be associated with malignancy.

IgG4-related kidney disease--A review.

IgG4-related disease (IgG4-RD) is a recently recognized systemic autoimmune disorder characterized by high levels of serum IgG4 and dense infiltration of IgG4-positive plasma cells in multiple organs. The condition was first described as a disease of the pancreas, and has since been recognized in various organ systems including the kidneys. IgG4 related kidney disease (IgG4-RKD) signifies any form of renal involvement by IgG4-RD. The most common renal involvement by IgG4-RD is tubulointerstitial nephritis. Glomerular disease, in particular membranous glomerulonephritis, may also be seen. Other co-existent glomerular diseases such as IgA nephropathy, membranoproliferative glomerulonephritis, and mesangioproliferative immune complex glomerulonephritis may be identified. IgG4-related plasma cell arteritis has also been noted in the kidney. As with IgG4-RD in general, IgG4 related kidney disease (IgG4-RKD) usually occurs in middle-aged to elderly men. Common findings in IgG4-RKD are plasma cell-rich interstitial inflammatory infiltrate either in a focal or diffuse pattern with increased IgG4+ plasma cells, expansile swirling interstitial fibrosis, high levels of serum IgG and IgG4, hypocomplementemia, high serum IgE levels and/or peripheral blood eosinophilia. By immunofluorescence, most of the cases show IgG4 dominant tubular basement membrane immune complex deposits. Similar to IgG4-RD, IgG4-RKD often shows a rapid response to steroid therapy. In this review, we discuss the current knowledge on IgG4-RKD and its clinical relevance.

Dream content in complicated grief: a window into loss-related cognitive schemas.

Bereavement and its accompanying psychological response (grief) constitute potent experiences that necessitate the reorganization of cognitive-affective representations of lost significant attachment figures during both wakefulness and dreaming. The goals of this preliminary study were to explore whether the dream content of 77 adults with complicated grief (CG) differed from that of a normative sample and whether CG patients who dream of the deceased differ from CG patients who do not dream of the deceased on measures of daytime emotional distress. CG dreams were characterized by more family and familiar characters including the deceased (in women), and fewer social interactions and emotions compared to norms. Increased representations of familiar characters in CG dreams may reflect attempts to reorganize relational cognitive schemas to compensate for the loss.

Impact of concurrent naturalistic pharmacotherapy on psychotherapy of complicated grief.

Complicated grief (CG) is a debilitating syndrome that can be reliably identified, but there is a paucity of research examining treatment of CG. A targeted psychotherapy for complicated grief (CGT) was recently shown to be efficacious [Shear, K., Frank, E., Houck, P.R., Reynolds, C.F., 3rd, 2005. Treatment of complicated grief: a randomized controlled trial. Journal of the American Medical Association 293, 2601-2608]. We provide a detailed examination of the association of naturalistic pharmacotherapy use with treatment response and study completion in the psychotherapy study. Patients on an antidepressant medication were more likely to complete a full course of CGT (91% vs. 58% completed), while antidepressant use had no effect on completion rates for the comparator, interpersonal psychotherapy (70% vs. 77%). Our naturalistic data underscore the need for prospective, randomized controlled studies of CG pharmacotherapy and psychotherapy alone and in combination.

Evaluation of whole slide image immunohistochemistry interpretation in challenging prostate needle biopsies.

Whole slide images (WSIs), also known as virtual slides, can support electronic distribution of immunohistochemistry (IHC) stains to pathologists that rely on remote sites for these services. This may lead to improvement in turnaround times, reduction of courier costs, fewer errors in slide distribution, and automated image analyses. Although this approach is practiced de facto today in some large laboratories, there are no clinical validation studies on this approach. Our retrospective study evaluated the interpretation of IHC stains performed in difficult prostate biopsies using WSIs. The study included 30 foci with IHC stains identified by the original pathologist as both difficult and pivotal to the final diagnosis. WSIs were created from the glass slides using a scanning robot (T2, Aperio Technologies, Vista, CA). An evaluation form was designed to capture data in 2 phases: (1) interpretation of WSIs and (2) interpretation of glass slides. Data included stain interpretations, diagnoses, and other parameters such as time required to diagnose and image/slide quality. Data were also collected from an expert prostate pathologist, consensus meetings, and a poststudy focus group. WSI diagnostic validity (intraobserver pairwise kappa statistics) was "almost perfect" for 1 pathologist, "substantial" for 3 pathologists, and "moderate" for 1 pathologist. Diagnostic agreement between the final/consensus diagnoses of the group and those of the domain expert was "almost perfect" (kappa = 0.817). Except for one instance, WSI technology was not felt to be the cause of disagreements. These results are encouraging and compare favorably with other efforts to quantify diagnostic variability in surgical pathology. With thorough training, careful validation of specific applications, and regular postsignout review of glass IHC slides (eg, quality assurance review), WSI technology can be used for IHC stain interpretation.

Telemedicine process used to implement an effective and functional screening program for diabetic retinopathy.

BACKGROUND: Diabetic retinopathy, damage to the blood vessels in the retina, is the leading cause of blindness in adults 20-74 years of age. Nearly 300 million people worldwide have diabetes and nearly half of all people with diabetes will develop some degree of diabetic retinopathy during their lifetime. It has been estimated that blindness from diabetic retinopathy is preventable in at least 65% of cases, if detected early. The aim of the project was to develop a flexible, modular, mobile method for screening individuals that could be used effectively in a variety of medical and community settings. METHODS: Our project created software to support a simple, effective retinal screening process for people with diabetes. The system included four separate software components: registration, imaging, grading, and tracking/reporting. The imaging component consisted of customized software running on a computer attached to a camera that drives retinal image acquisition. RESULTS: Seven hundred and six subjects with diabetes were successfully consented, registered, imaged, and had their eye images graded. The mean time for subjects to be registered, imaged, and have eye images graded was 00:12:53. Seventy-six percent of the sample was instructed to follow-up with their eye doctor in 1 year (had no retinopathy or microaneurysms). Only six patients (0.8 %) were asked to see their eye doctor within 6 weeks (proliferative retinopathy or diabetic maculopathy). CONCLUSION: Our project successfully demonstrated that the retinal screening software and workflow process can be used to overcome challenges of providing adequate screening and diagnostic services for people at risk for diabetic retinopathy.

The prevalence and correlates of psychiatric comorbidity in individuals with complicated grief.

BACKGROUND: Complicated grief (CG), variously called pathological or traumatic grief, is a debilitating syndrome that is not currently included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) nomenclature. One issue that remains under debate is whether this condition can be clearly distinguished from other psychiatric disorders, such as major depression and posttraumatic stress disorder, with which CG frequently coexists. METHODS: Using a structured clinical interview for CG and the Structured Clinical Interview for DSM-IV, trained experienced raters conducted careful diagnostic assessments of individuals seeking treatment of bereavement-related distress. All study participants met criteria for a current CG syndrome. Liberal criteria were used to diagnose DSM-IV disorders, making no attempt to decide if symptoms could be explained by grief. RESULTS: Of 206 who met the criteria for CG, 25% had no evidence of a current DSM-IV Axis I disorder. When present, psychiatric comorbidity was associated with significantly greater severity of grief; however, even after adjustment for the presence of comorbidity, severity of CG symptoms was associated with greater work and social impairment. LIMITATIONS: It is likely that our study underestimated the rate of CG without comorbidity because fewer DSM diagnoses would have been made if a judgment about grief had been taken into consideration. CONCLUSIONS: Our data provide further support for the need to identify CG as a psychiatric disorder.

Treating complicated grief and substance use disorders: a pilot study.

Empirically supported treatments for co-occurring substance use disorders (SUDs) and grief problems are lacking, despite the salience of grief pathology in substance abusers. Identification of a syndrome of complicated grief, distinct from bereavement-related depression and anxiety, led to the development of a targeted treatment, but this treatment has not been tried with persons with SUDs. We recruited 16 adults with complicated grief and substance dependence or abuse into an open pilot study of a manualized 24-session treatment, incorporating motivational interviewing and emotion coping and communication skills into our efficacious complicated grief treatment. Completer and intent-to-treat analyses showed significant reductions in Inventory of Complicated Grief and Beck Depression Inventory scores, with large effect sizes. Timeline Followback percent days abstinent increased significantly in both analyses, with medium to large effect sizes, and cravings declined significantly. Study limitations notwithstanding, complicated grief and substance use treatment appears to be a promising intervention that merits further research.

Indirect self-destructive behavior and overt suicidality in patients with complicated grief.

BACKGROUND: Complicated grief is associated with increased suicidal ideation in samples of bereaved individuals; however, suicidal behavior has not been assessed in these patients. Additionally, there are no reports of suicidality among help-seeking individuals with complicated grief. Therefore, we examined suicidal behavior and its correlates in 149 patients who signed informed consent statements to participate in a National Institute of Mental Health-funded treatment study of complicated grief. METHOD: All patients met criteria for complicated grief (Inventory of Complicated Grief score>or=25). Suicidality was assessed using a structured clinical interview administered prior to beginning treatment. Participants also completed self-report questionnaires and interview assessment measures rating the presence or absence of DSM-IV Axis I diagnosis and symptom severity. Data were gathered between April 2001 and April 2004. RESULTS: Thoughts of wanting to die following the death of a loved one were reported by 65% of participants. More than half of this group (38% of the study sample) engaged in self-destructive behavior, including 9% who made a suicide attempt and 29% who engaged in indirect suicidal behavior. In a multiple logistic regression model, only the severity of complicated grief symptoms (p<.0001) and history of a suicide attempt (p<.02) were significantly associated with postloss suicidal behavior. DISCUSSION: Consistent with reports of non-help-seeking bereaved people, a high rate of individuals seeking treatment for complicated grief endorsed a wish to die. Notably, 13% of this group made at least 1 suicide attempt, and 44% engaged in indirect self-destructive behavior. Given its frequency, this behavior should be included in assessment of bereaved people.