Cost-effectiveness of Multidisciplinary Care in Plastic Surgery: A Systematic Review.

BACKGROUND: Multidisciplinary care has been previously shown to improve outcomes for patients and providers alike, fostering interprofessional collaboration and communication. Many studies have demonstrated the beneficial health care outcomes of interdisciplinary care. However, there has been minimal focus on the cost-effectiveness of such care, particularly in the realm of plastic surgery. This is the first systematic review to examine cost savings attributable to plastic surgery involvement in multidisciplinary care. METHODS: A comprehensive literature review of articles published on cost outcomes associated with multidisciplinary teams including a plastic surgeon was performed. Included articles reported on cost outcomes directly or indirectly attributable to a collaborative intervention. Explicitly reported cost savings were totaled on a per-patient basis. Each article was also reviewed to determine whether the authors ultimately recommended the team-based intervention described. RESULTS: A total of 604 articles were identified in the initial query, of which 8 met the inclusion criteria. Three studies reported explicit cost savings from multidisciplinary care, with cost savings ranging from $707 to $26,098 per patient, and 5 studies reported changes in secondary factors such as complication rates and length of stay. All studies ultimately recommended multidisciplinary care, regardless of whether cost savings were achieved. CONCLUSIONS: This systematic review of the cost-effectiveness of multidisciplinary plastic surgery care examined both primary cost savings and associated quality outcomes, such as length of stay, complication rate, and resource consumption. Our findings indicate that the inclusion of plastic surgery in team-based care provides both direct and indirect cost savings to all involved parties.

Restoration of metabolic health by decreased consumption of branched-chain amino acids.

KEY POINTS: We recently found that feeding healthy mice a diet with reduced levels of branched-chain amino acids (BCAAs), which are associated with insulin resistance in both humans and rodents, modestly improves glucose tolerance and slows fat mass gain. In the present study, we show that a reduced BCAA diet promotes rapid fat mass loss without calorie restriction in obese mice. Selective reduction of dietary BCAAs also restores glucose tolerance and insulin sensitivity to obese mice, even as they continue to consume a high-fat, high-sugar diet. A low BCAA diet transiently induces FGF21 (fibroblast growth factor 21) and increases energy expenditure. We suggest that dietary protein quality (i.e. the precise macronutrient composition of dietary protein) may impact the effectiveness of weight loss diets. ABSTRACT: Obesity and diabetes are increasing problems around the world, and although even moderate weight loss can improve metabolic health, reduced calorie diets are notoriously difficult to sustain. Branched-chain amino acids (BCAAs; leucine, isoleucine and valine) are elevated in the blood of obese, insulin-resistant humans and rodents. We recently demonstrated that specifically reducing dietary levels of BCAAs has beneficial effects on the metabolic health of young, growing mice, improving glucose tolerance and modestly slowing fat mass gain. In the present study, we examine the hypothesis that reducing dietary BCAAs will promote weight loss, reduce adiposity, and improve blood glucose control in diet-induced obese mice with pre-existing metabolic syndrome. We find that specifically reducing dietary BCAAs rapidly reverses diet-induced obesity and improves glucoregulatory control in diet-induced obese mice. Most dramatically, mice eating an otherwise unhealthy high-calorie, high-sugar Western diet with reduced levels of BCAAs lost weight and fat mass rapidly until regaining a normal weight. Importantly, this normalization of weight was mediated not by caloric restriction or increased activity, but by increased energy expenditure, and was accompanied by a transient induction of the energy balance regulating hormone FGF21 (fibroblast growth factor 21). Consumption of a Western diet reduced in BCAAs was also accompanied by a dramatic improvement in glucose tolerance and insulin resistance. Our results link dietary BCAAs with the regulation of metabolic health and energy balance in obese animals, and suggest that specifically reducing dietary BCAAs may represent a highly translatable option for the treatment of obesity and insulin resistance.

EmoCodes: a Standardized Coding System for Socio-emotional Content in Complex Video Stimuli.

Social information processing is vital for inferring emotional states in others, yet affective neuroscience has only begun to scratch the surface of how we represent emotional information in the brain. Most previous affective neuroscience work has used isolated stimuli such as static images of affective faces or scenes to probe affective processing. While this work has provided rich insight to the initial stages of emotion processing (encoding cues), activation to isolated stimuli provides limited insight into later phases of emotion processing such as interpretation of cues or interactions between cues and established cognitive schemas. Recent work has highlighted the potential value of using complex video stimuli to probe socio-emotional processing, highlighting the need to develop standardized video coding schemas as this exciting field expands. Toward that end, we present a standardized and open-source coding system for complex videos, two fully coded videos, and a video and code processing Python library. The EmoCodes manual coding system provides an externally validated and replicable system for coding complex cartoon stimuli, with future plans to validate the system for other video types. The emocodes Python library provides automated tools for extracting low-level features from video files as well as tools for summarizing and analyzing the manual codes for suitability of use in neuroimaging analysis. Materials can be freely accessed at https://emocodes.org/. These tools represent an important step toward replicable and standardized study of socio-emotional processing using complex video stimuli. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00100-7.

Impact of the Virtual Format on Plastic Surgery Residency and Fellowship Interviews: A National Cross-Sectional Study.

BACKGROUND: The 2020 to 2021 residency and fellowship application cycles were profoundly affected by the introduction of virtual interviews. The authors investigated the impact the virtual format had on plastic surgery residency and fellowship interviews from the perspectives of program directors. METHODS: Surveys were sent to program directors of integrated plastic surgery residency and fellowship programs to ascertain their perspectives regarding the virtual format's impact on residency and fellowship interviews. Program directors were stratified into residency and fellowship cohorts, and comparative analysis was performed. RESULTS: Ninety-two program directors, 28 from integrated plastic surgery residency programs and 64 from fellowship programs, completed our survey (35 percent). Compared to in-person interviews, virtual interviews were reported to be more economical and time efficient by program directors of residency (100 percent and 46 percent, respectively) and fellowship programs (97 percent and 48 percent, respectively). Consequentially, 36 percent and 47 percent of residency and fellowship programs were able to interview more applicants, respectively. Program directors of residency and fellowship programs reported that virtual interviews hindered their ability to assess applicants' fit with the program (75 percent and 63 percent, respectively), personality and communication skills (75 percent and 64 percent, respectively), and commitment to the field, along with their ability to function as a trainee (57 percent and 50 percent, respectively). Overall, 71 percent of program directors of residency and 58 percent of program directors of fellowship programs preferred in-person interviews. The majority of residency (71 percent) and fellowship (56 percent) program directors intend to conduct both in-person and virtual interviews in future application cycles ( p = 0.12). CONCLUSIONS: Despite preferring in-person interviews, program directors intend to host both in-person and virtual interviews in future application cycles. It remains to be seen how virtual interviews will be used moving forward.

Multimodal examination of emotion processing systems associated with negative affectivity across early childhood.

High Temperamental Negative Affectivity in early childhood has been found to predict later emotion dysregulation. While much work has been conducted to separately probe bio-behavioral systems associated with Negative Affectivity, very little work has examined the relations among multiple systems across age. In this study, we use multi-modal methods to index neurobiological systems associated with Negative Affectivity in 53 4-7-year-old children. Prefrontal activation during emotion regulation was measured using functional near-infrared spectroscopy over the lateral prefrontal cortex (PFC) while children played a game designed to elicit frustration in Social (Happy and Angry faces) and Nonsocial contexts. Gaze behaviors while free-viewing Happy and Angry faces were also measured. Finally, Negative Affectivity was indexed using a score composite based on factor analysis of parent-reported temperament. Using mixed-effects linear models, we found an age-dependent association between Negative Affectivity and both PFC activation during frustration and fixation duration on the mouth area of Happy faces, such that older children high in Negative Affectivity spent less time looking at the mouths of Happy faces and had lower PFC activation in response to frustration (ps<0.034). These results provide further insight to how Negative Affectivity may be associated with changes in affective neurobiological systems across early childhood.

Adversity is Linked with Decreased Parent-Child Behavioral and Neural Synchrony.

Parent-child synchrony-parent-child interaction patterns characterized by contingent social responding, mutual responsivity, and co-regulation-has been robustly associated with adaptive child outcomes. Synchrony has been investigated in both behavioral and biological frameworks. While it has been demonstrated that adversity can influence behavioral parent-child synchrony, the neural mechanisms by which this disruption occurs are understudied. The current study examined the association between adversity, parent-child behavioral synchrony, and parent-child neural synchrony across lateral prefrontal cortical regions using functional near-infrared spectroscopy hyperscanning during a parent-child interaction task that included a mild stress induction followed by a recovery period. Participants included 115 children (ages 4-5) and their primary caregivers. Parent-child behavioral synchrony was quantified as the amount time the dyad was synchronous (e.g., reciprocal communication, coordinated behaviors) during the interaction task. Parent-child neural synchrony was examined as the hemodynamic concordance between parent and child lateral PFC activation. Adversity was examined across two, empirically-derived domains: sociodemographic risk (e.g., family income) and familial risk (e.g., household chaos). Adversity, across domains, was associated with decreased parent-child behavioral synchrony across task conditions. Sociodemographic risk was associated with decreased parent-child neural synchrony in the context of experimentally-induced stress. These findings link adversity to decreased parent-child behavioral and neural synchrony.

Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and lifespan in mice.

Protein restricted (PR) diets promote health and longevity in many species. While the precise components of a PR diet that mediate the beneficial effects to longevity have not been defined, we recently showed that many metabolic effects of PR can be attributed to reduced dietary levels of the branched-chain amino acids (BCAAs) leucine, isoleucine, and valine. Here, we demonstrate that restricting dietary BCAAs increases the survival of two different progeroid mouse models, delays frailty and promotes the metabolic health of wild-type C57BL/6J mice when started in midlife, and leads to a 30% increase in lifespan and a reduction in frailty in male, but not female, wild-type mice when fed lifelong. Our results demonstrate that restricting dietary BCAAs can increase healthspan and longevity in mice, and suggest that reducing dietary BCAAs may hold potential as a translatable intervention to promote healthy aging.

A multifaceted intervention to implement guidelines improved treatment of nursing home-acquired pneumonia in a state veterans home.

OBJECTIVES: To assess the feasibility of a multifaceted strategy to translate evidence-based guidelines for treating nursing home-acquired pneumonia (NHAP) into practice using a small intervention trial. DESIGN: Pre-posttest with untreated control group. SETTING: Two Colorado State Veterans Homes (SVHs) during two influenza seasons. PARTICIPANTS: Eighty-six residents with two or more signs of lower respiratory tract infection. INTERVENTION: Multifaceted, including a formative phase to modify the intervention, institutional-level change emphasizing immunization, and availability of appropriate antibiotics; interactive educational sessions for nurses; and academic detailing. MEASUREMENTS: Subjects' SVH medical records were reviewed for guideline compliance retrospectively for the influenza season before the intervention and prospectively during the intervention. Bivariate comparisons-of-care processes between the intervention and control facility before and after the intervention were made using the Fischer exact test. RESULTS: At the intervention facility, compliance with five of the guidelines improved: influenza vaccination, timely physician response to illness onset, x-ray for patients not being hospitalized, use of appropriate antibiotics, and timely antibiotic initiation for unstable patients. Chest x-ray and appropriate and timely antibiotics were significantly better at the intervention than at the control facility during the intervention year but not during the control year. CONCLUSION: Multifaceted, evidence-based, NHAP guideline implementation improved care processes in a SVH. Guideline implementation should be studied in a national sample of nursing homes to determine whether it improves quality of life and functional outcomes of this debilitating illness for long-term care residents.

Assessments of the chemistry and vasodilatory activity of nitrite with hemoglobin under physiologically relevant conditions.

Hypoxic vasodilation involves detection of the oxygen content of blood by a sensor, which rapidly transduces this signal into vasodilatory bioactivity. Current perspectives on the molecular mechanism of this function hold that hemoglobin (Hb) operates as both oxygen sensor and a condition-responsive NO reactor that regulates the dispensing of bioactivity through release of the NO group from the beta-cys93 S-nitroso derivative of Hb, SNO-Hb. A common path to the formation of SNO-Hb involves oxidative transfer of the NO-group from heme to thiol. We have previously reported that the reaction of nitrite with deoxy-Hb, which furnishes heme-Fe(II)NO, represents one attractive route for the formation of SNO-Hb. Recent literature, however, posits that the nitrite-reductase reaction of Hb might produce physiological vasodilatory effects through NO that evades trapping on heme-Fe(II) and may be stored before release as Fe(III)NO. In this article, we briefly review current perspectives in NO biology on the nitrite-reductase reaction of Hb. We report in vitro spectroscopic (UV/Vis, EPR) studies that are difficult to reconcile with suggestions that this reaction either generates a heme-Fe(III)NO reservoir or significantly liberates NO. We further show in bioassay experiments that combinations of nitrite and deoxy-Hb--under conditions that suppress SNO-Hb formation--exhibit no direct vasodilatory activity. These results help underscore the differences between physiological, RBC-regulated, hypoxic vasodilation versus pharmacological effects of exogenous nitrite.

Perforated duodenal ulcer: An unusual manifestation of allergic eosinophilic gastroenteritis.

Spontaneous perforation of a duodenal ulcer secondary to allergic eosinophilic gastroenteritis (EGE) has not been previously reported. We present such a case in a teenager who presented with peritonitis. After exploration and operative repair of his ulcer, he continued to experience intermittent abdominal pain, and further evaluation revealed eosinophilic gastroenteritis in the setting of multiple food allergies. His EGE resolved after adhering to a restrictive diet. Both duodenal ulcers and EGE are very rarely seen in pediatric patients. EGE has a variable presentation depending on the layer(s) of bowel wall affected and the segment of the gastrointestinal tract that is involved. Once diagnosed, it may respond to dietary changes in patients with recognized food allergies, or to steroids in patients in whom an underlying cause is not identified. Our case highlights the need to keep EGE in the differential diagnosis when treating pediatric patients with duodenal ulcers. The epidemiology, pathophysiology, and treatment of EGE are also discussed, along with a review of the current literature.

Significance of C4d Immunostaining in Placental Chronic Intervillositis.

Deposition of the complement split product C4d is a phenomenon studied extensively as a marker for complement activation in antibody-mediated transplant rejection. C4d also is observed in placental disease processes including spontaneous abortion, infarct, and villitis of unknown origins. Massive chronic intervillositis is a rare placental abnormality associated with increased risk of growth restriction, fetal death, and recurrent fetal loss. In this study, we evaluated C4d immunostaining in placentas with accumulation of intervillous monocytes with and without villitis. Archived placentas from Kosair Children's Hospital (Louisville, KY) and Seattle Children's Hospital (Seattle, WA) were selected and divided into 4 groups, 16 cases of intervillositis with complicated pregnancy, 15 cases of uncomplicated intervillositis, 20 cases of complicated villitis, and 13 cases of uncomplicated villitis, all with varying degrees of monocytic cells in the intervillous space. Representative specimen blocks were immunohistochemically stained for C4d. The percentage of positive staining of the microvillous surface of the syncytiotrophoblast was scored by five pathologists, and the following consensus score was determined: 0  =  0% to 5%; 1  =  5% to 25%; 2  =  25% to 75%; and 3 ≥ 75%. C4d immunostain localized to the microvillous border of syncytiotrophoblast in many of the placentas. C4d staining was more strongly associated with intervillositis than with villitis (odds ratio: 6.3; confidence interval: 2.1-18.7; P  =  0.001).

Androgen receptor immunohistochemistry in genitourinary neoplasms.

PURPOSE: Androgen receptor (AR) is a recognized immunohistochemical marker of prostate cancer. However, the sensitivity and specificity of AR for prostate cancer in the setting of other genitourinary neoplasms has not been rigorously studied. METHODS: We employed tissue microarrays containing prostate carcinomas, urothelial carcinomas, renal cell carcinomas, and testicular neoplasms. Slides were stained immunohistochemically for AR. RESULTS: Androgen receptor was positive in 95% of prostate carcinomas (n=230), but 19% of invasive urothelial carcinomas of the bladder (n=190) and 33% of non-invasive bladder urothelial carcinomas were also AR positive (N=107). Furthermore, 16% of renal pelvis urothelial carcinomas (n=43) were positive. Of primary renal cell carcinomas, 19% were AR positive (n=307). From a metastatic renal cell carcinoma cohort, 28% of metastases were AR positive (N=126). Six percent of non-teratomatous testicular germ cell tumors stained for AR (n=103). CONCLUSIONS: Our data show that the sensitivity of AR immunohistochemistry for prostate cancer is 94.8%. However, the specificity of AR is only 81.4%, among our cohort of invasive genitourinary tumors. Thus, we find the specificity of AR suboptimal, yet AR may remain useful as a component of an immunostain panel.

Utility of immunohistochemical markers in irradiated breast tissue: an analysis of the role of myoepithelial markers, p53, and Ki-67.

Radiation therapy is an important adjunct to breast-conserving surgery, but the diagnosis of recurrent/de novo carcinoma in a background of radiation atypia can be difficult, especially on small biopsies. Immunostaining for myoepithelial cell proteins is often used to assess invasion in nonirradiated breast tissue, yet these stains have not been investigated specifically in irradiated breast. We studied 29 irradiated breast resection specimens, some with carcinoma in situ (CIS, n=13) and/or invasive carcinoma (n=13). Representative blocks were stained for the myoepithelial proteins p63, smooth muscle myosin heavy chain (SMM), calponin, CK5/6, the proliferative marker Ki-67, and the tumor-suppressor p53. Nonirradiated control tissue was also stained with Ki-67 and p53 (CIS, normal, contralateral). Areas of radiation atypia/atrophy and nearly all CIS in irradiated breast tissue had abundant myoepithelial cells as evidenced by SMM, calponin, and p63 stains, with focal staining attenuation or gaps with SMM and calponin and frequently absent CK5/6 staining. As predicted, myoepithelial cell staining was absent in invasive carcinoma. p63 staining revealed postradiation myoepithelial nuclear morphologic changes. p53 staining was increased, although weak, in irradiated non-neoplastic breast (12% irradiated; 4% nonirradiated); however, irradiated CIS had less p53 staining when compared with control CIS (3% irradiated; 38% nonirradiated). As expected, Ki-67 was increased in carcinoma as compared with non-neoplastic irradiated tissue. Thus, myoepithelial immunostaining is a useful diagnostic adjunct in irradiated breast, with caveats similar to nonirradiated breast. Ki-67 may be helpful in some postradiation specimens; however, p53 staining is not reliable in this setting.

High-energy particle-induced tumorigenesis throughout the gastrointestinal tract.

Epidemiological data reveals the gastrointestinal (GI) tract as one of the main sites for low-LET radiation-induced cancers. Importantly, the use of particle therapy is increasing, but cancer risk by high-LET particles is still poorly understood. This gap in our knowledge also remains a major limiting factor in planning long-term space missions. Therefore, assessing risks and identifying predisposing factors for carcinogenesis induced by particle radiation is crucial for both astronauts and cancer survivors. We have previously shown that exposure to relatively high doses of high-energy (56)Fe ions induced higher intestinal tumor frequency and grade in the small intestine of Apc(Min/+) mice than γ rays. However, due to the high number of spontaneous lesions (∼30) that develop in Apc(Min/+) animals, this Apc mutant model is not suitable to investigate effects of cumulative doses <1 Gy, which are relevant for risk assessment in astronauts and particle radiotherapy patients. However, Apc(1638N/+) mice develop a relatively small number of spontaneous lesions (∼3 per animal) in both small intestine and colon, and thus we propose a better model for studies on radiation-induced carcinogenesis. Here, we investigated model particle radiation increases tumor frequency and grade in the entire gastrointestinal tract (stomach and more distal intestine) after high- and low-radiation doses whether in the Apc(1638N/+). We have previously reported that an increase in small intestinal tumor multiplicity after exposure to γ rays was dependent on gender in Apc(1638N/+) mice, and here we investigated responses to particle radiation in the same model. Phenotypical and histopathological observations were accompanied by late changes in number and position of mitotic cells in intestinal crypts from animals exposed to different radiation types.

Naturally occurring murine norovirus infection in a large research institution.

Murine norovirus (MNV) is a recently discovered infectious agent in mice and may be the most common naturally occurring infection of laboratory mice in North America. In 2005, we surveyed the Swiss Webster female sentinel mice in our institute's research facilities. Of the 4 facilities surveyed, 3 had sentinel mice that were positive for MNV antibodies, whereas our largest facility (which only receives mice directly from select vendors or by embryo rederivation directly into the facility) was apparently MNV-free. However, testing of sentinel mice in this large facility 1 y later found that 2% of the animals had developed MNV-specific antibodies. In a recently opened fifth facility, a serologic survey in 2006 identified MNV-antibody-positive Tac:SW sentinel mice that had received bedding from experimental mice on the same rack quadrant. Reverse transcription- polymerase chain reaction analysis of feces from the cages of these mice showed evidence for shedding of MNV. These sentinel mice were used to study the fecal excretion, antibody development, gross lesions upon necropsy, histopathology, and immunohistochemistry of the viral infection. None of the MNV-antibody-positive sentinel mice exhibited clinical signs or gross lesions, but these mice excreted virus in feces and developed antibodies to MNV. Histopathologic lesions consisted only of a few hepatic inflammatory foci in each liver section, some of which were immunoreactive with antibodies to MNV. MNV viral antigens also were present in the mesenteric lymph nodes.

Routes to S-nitroso-hemoglobin formation with heme redox and preferential reactivity in the beta subunits.

Previous studies of the interactions of NO with human hemoglobin have implied the predominance of reaction channels that alternatively eliminate NO by converting it to nitrate, or tightly complex it on the alpha subunit ferrous hemes. Both channels could effectively quench NO bioactivity. More recent work has raised the idea that NO groups can efficiently transfer from the hemes to cysteine thiols within the beta subunit (cysbeta-93) to form bioactive nitrosothiols. The regulation of NO function, through its chemical position in the hemoglobin, is supported by response to oxygen and to redox agents that modulate the molecular and electronic structure of the protein. In this article, we focus on reactions in which Fe(III) hemes could provide the oxidative requirements of this NO-group transfer chemistry. We report a detailed investigation of the reductive nitrosylation of human met-Hb, in which we demonstrate the production of S-nitroso (SNO)-Hb through a heme-Fe(III)NO intermediate. The production of SNO-Hb is strongly favored (over nitrite) when NO is gradually introduced in limited total quantities; in this situation, moreover, heme nitrosylation occurs primarily within the beta subunits of the hemoglobin tetramer. SNO-Hb can similarly be produced when Fe(II)NO hemes are subjected to mild oxidation. The reaction of deoxygenated hemoglobin with limited quantities of nitrite leads to the production of beta subunit Fe(II)NO hemes, with SNO-Hb produced on subsequent oxygenation. The common theme of these reactions is the effective coupling of heme-iron and NO redox chemistries. Collectively, they establish a connectivity between hemes and thiols in Hb, through which NO is readily dislodged from storage on the heme to form bioactive SNO-Hb.