Executive function deficits in congenital heart surgical patients: prevalence and timing of presentation.

BACKGROUND: Congenital heart patients undergoing congenital heart surgery in the first year of life are at high risk of having a neurodevelopmental disorder. The most common difficulties are related to executive functioning. The following questions were assessed in the current project: Are patients having congenital heart surgery after one year of life at lower risk for neurodevelopmental disorders? At what age do executive function deficits manifest? METHODS: We evaluated executive function in four groups of congenital heart patients who had undergone congenital heart surgery. These groups were high-risk patients with and without a genetic syndrome associated with a neurodevelopmental disorder and low-risk patients with and without a genetic syndrome associated with a neurodevelopmental disorder. We evaluated executive function using the Behavior Rating Inventory of Executive Function - Preschool Version, Behavior Rating Inventory of Executive Function-2, and Minnesota Executive Function Scale at various ages. We compared the rates of executive function deficits in the high- and low-risk groups as well as compared that to the published norms for age. We also assessed at what age these deficits become apparent. CONCLUSION: We found that both high- and low-risk groups had higher levels of executive functioning deficits compared to the norms for age. The low-risk group's degree of executive function deficits appeared a little lower than the high-risk group. However, it was difficult to comment on the statistical significance. We also saw that executive function deficits often do not become apparent for many years after surgery. This finding highlights the need for continued evaluation of functioning as these kids mature.

Disparities in treatment and survival in early-stage hepatocellular carcinoma in California.

BACKGROUND AND OBJECTIVES: Curative intent therapy is the standard of care for early-stage hepatocellular carcinoma (HCC). However, these therapies are under-utilized, with several treatment and survival disparities. We sought to demonstrate whether the type of facility and distance from treatment center (with transplant capabilities) contributed to disparities in curative-intent treatment and survival for early-stage HCC in California. METHODS: We performed a retrospective analysis of the California Cancer Registry for patients diagnosed with stage I or II primary HCC between 2005 and 2017. Primary and secondary outcomes were receipt of treatment and overall survival, respectively. Multivariable logistic regression and Multivariable Cox proportional hazards regression were used to evaluate associations. RESULTS: Of 19 059 patients with early-stage HCC, only 36% (6778) received curative-intent treatment. Compared to Non-Hispanic White patients, Hispanic patients were less likely, and Asian/Pacific Islander patients were more likely to receive curative-intent treatment. Our results showed that rural residence, public insurance, lower neighborhood SES, and care at non-National Cancer Institute-designated cancer center were associated with not receiving treatment and decreased survival. CONCLUSIONS: Although multiple factors influence receipt of treatment for early-HCC, our findings suggest that early intervention programs should target travel barriers and access to specialist care to help improve oncologic outcomes.

Human soft tissue sarcomas harbor an intratumoral viral microbiome which is linked with natural killer cell infiltrate and prognosis.

BACKGROUND: Groundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures. METHODS: We prospectively obtained tumor and stool samples from adult patients with non-metastatic STS using a strict sterile collection protocol to minimize contamination. Metagenomic classification was used to estimate abundance using genus and species taxonomic levels across all classified organisms, and data were analyzed with respect to clinicopathologic factors. RESULTS: Fifteen patients were enrolled. Most tumors were located at an extremity (67%) and were histologic grade 3 (87%). 40% were well-differentiated/dedifferentiated liposarcoma histology. With a median follow-up of 24 months, 4 (27%) patients developed metastases, and 3 (20%) died. Despite overwhelming human DNA (>99%) intratumorally, we detected a small but consistent proportion of bacterial DNA (0.02-0.03%) in all tumors, including Proteobacteria, Bacteroidetes, and Firmicutes, as well as viral species. In the tumor microenvironment, we observed a strong positive correlation between viral relative abundance and natural killer (NK) infiltration, and higher NK infiltration was associated with superior metastasis-free and overall survival by immunohistochemical, flow cytometry, and multiplex immunofluorescence analyses. CONCLUSIONS: We prospectively demonstrate the presence of a distinct and measurable intratumoral microbiome in patients with STS at multiple time points. Our data suggest that the STS tumor microbiome has prognostic significance with viral relative abundance associated with NK infiltration and oncologic outcome. Additional studies are warranted to further assess the clinical impact of these findings.

Emergency department visit patterns in the recently discharged, violently injured patient: Retrospective cohort review.

BACKGROUND: Analysis of the costs associated with emergency department (ED) visits after discharge for violent injury could highlight subgroups for the development of cost-effective interventions to support healing and prevent treatment failures in violently injured patients. METHODS: A retrospective cohort review was conducted of all patients with return ED visits within 90 days of discharge after treatment for a violent injury occurring between July 1, 2016, and June 30, 2018. Hospital costs were calculated for each incidence and analyzed against demographic and injury type variables to identify trends. RESULTS: 218 return ED visits were identified. Hospital costs showed a high frequency of low-cost visits. For more complex visits, distinct cost patterns were observed for Black and LatinX males compared to White males as a function of age. CONCLUSIONS: Analysis of hospital cost per visit identified trends among different subgroups. Underlying etiologies presumably vary between groups, but hypothesis-driven further investigation and needs assessment is required. Understanding the driving forces behind these cost trends may aid in developing effective interventions.

Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials.

The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.

Research-Driven Guidelines for Delivering Group Exercise Programs via Videoconferencing to Older Adults.

Telehealth holds much potential for supporting older adults' physical and social health. In particular, telewellness interventions to support the physical and social wellness of older adults are needed to overcome participation barriers with in-person programs. This paper presents guidelines for delivering telewellness interventions to older adults, which were informed by a human factors approach to developing a Tele Tai Chi intervention for older adults with mobility disabilities, including reviewing user needs literature and conducting user-centered needs assessment research. From these findings, we developed a protocol and support materials for delivering a telewellness intervention and conducted a feasibility study. We also established an adaptation committee to provide recommendations on the intervention. The outcome of our human factors approach was the establishment of research-driven design guidelines for delivering group exercise programs to older adults using videoconferencing. The guidelines provide direction for designing a telewellness protocol, supporting remote participation, and promoting socialization and engagement. These guidelines can be used to deliver interventions that increase access to socially-engaging, physical activity programs for older adults, which can ultimately help support their physical health, mental health, and quality of life.

The Impact of Preexisting Psychiatric Disorders on Outcomes After Pancreatic Cancer Surgery.

OBJECTIVES: Comorbid psychiatric illness has been associated with worse outcomes after some major surgical procedures. We hypothesized that patients with preexisting mood disorders would have worse postoperative and oncologic outcomes after pancreatic cancer resection. METHODS: This retrospective cohort study analyzed Surveillance, Epidemiology, and End Results patients with resectable pancreatic adenocarcinoma. A preexisting mood disorder was classified if a patient was diagnosed and/or treated with medication approved for depression/anxiety within 6 months before surgery. RESULTS: Of 1305 patients, 16% had a preexisting mood disorder. Mood disorders had no impact on hospital length of stay (12.9 vs 13.2 days, P = 0.75), 30-day complications (26% vs 22%, P = 0.31), 30-day readmissions (26% vs 21%, P = 0.1), or mortality (30 days: 3% vs 4%, P = 0.35); only an increased 90-day readmissions rate (42% vs 31%, P = 0.001) was observed. No effect on adjuvant chemotherapy receipt (62.5% vs 69.2%, P = 0.06) or survival (24 months, 43% vs 39%, P = 0.44) was observed. CONCLUSIONS: Preexisting mood disorders influenced 90-day readmissions after pancreatic resection, but not other postoperative or oncologic outcomes. These findings suggest that affected patients should be expected to have outcomes similar to patients without mood disorders.

Search for a Variation of the Fine Structure Constant around the Supermassive Black Hole in Our Galactic Center.

Searching for space-time variations of the constants of Nature is a promising way to search for new physics beyond general relativity and the standard model motivated by unification theories and models of dark matter and dark energy. We propose a new way to search for a variation of the fine-structure constant using measurements of late-type evolved giant stars from the S star cluster orbiting the supermassive black hole in our Galactic Center. A measurement of the difference between distinct absorption lines (with different sensitivity to the fine structure constant) from a star leads to a direct estimate of a variation of the fine structure constant between the star's location and Earth. Using spectroscopic measurements of five stars, we obtain a constraint on the relative variation of the fine structure constant below 10^{-5}. This is the first time a varying constant of nature is searched for around a black hole and in a high gravitational potential. This analysis shows new ways the monitoring of stars in the Galactic Center can be used to probe fundamental physics.

Is there any effect of neurotrophin-3 on the pathogenesis of non-allergic nasal polyps?

BACKGROUND: Although the role of neurotrophins such as nerve growth factor and brain-derived neurotrophic factor in nasal polyps development has been studied, the contribution of neurotrophin-3 has not been evaluated yet. This study aimed to investigate the possible role of neurotrophin-3 in nasal polyps pathogenesis. METHODS: The study group comprised 70 non-allergic nasal polyps patients and the control group consisted of 53 patients with middle turbinate concha bullosa. Specimens were taken, during surgery, from the ethmoid sinus nasal polyps in the nasal polyps group and from the lateral part of the middle turbinate concha bullosa in the control group. Tissue and serum levels of neurotrophin-3 were assessed by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. RESULTS: Nasal polyps patients had higher tissue neurotrophin-3 scores (p < 0.001). There was no statistically significant difference between groups regarding serum neurotrophin-3 levels (p = 0.417). Tissue neurotrophin-3 staining scores in the nasal polyps group had no statistically significant correlation with Lund-Mackay scores (p = 0.792). CONCLUSION: Neurotrophin-3 may have a local effect in nasal polyps pathogenesis, without joining systemic circulation.

Delay in pediatric epilepsy surgery: A caregiver's perspective.

The timing of epilepsy surgery is complex, and there is not a structured pathway to help families decide whether to continue medical management or pursue surgical treatment. We surveyed caregivers of pediatric epilepsy surgery patients. Fifty-eight respondents answered the majority of questions. Thirty caregivers wished their child had undergone epilepsy surgery earlier compared with twenty who felt surgery was done at the appropriate time, and eight were unsure. In retrospect, caregivers who wished their child's surgery had been performed sooner had a significantly longer duration of epilepsy prior to the surgery [44.1±71.7 (months±standard deviation (SD), N=27)], compared with those who felt content with the timing of the surgery [12.8±14.1 (months±SD, N=20), p=0.0034]. Caregivers were willing to accept a lower likelihood of seizure freedom than their physician reported was likely. Most caregivers were willing to accept deficits in all domains surveyed; caregivers had high acceptance of motor deficits, cognitive deficits, behavioral change, and language loss. Future studies are needed to focus on how to improve the education of caregivers and neurologists about the benefits and risks of epilepsy surgery and accelerate the pipeline to epilepsy surgery to improve caregiver satisfaction.

Ecchordosis Physaliphora: Evaluation with Precontrast and Contrast-Enhanced Fast Imaging Employing Steady-State Acquisition MR Imaging Based on Proposed New Classification.

PURPOSE: Ecchordosis physaliphora (EP) is a notochordal remnant typically located at the dorsal surface of the clivus, which has to be distinguished from the other retroclival lesions. Our aim is to investigate the imaging features of intracranial EP using precontrast and contrast-enhanced fast imaging employing steady-state acquisition (FIESTA). METHODS: We retrospectively evaluated the precontrast and contrast-enhanced FIESTA images of 399 patients with temporal magnetic resonance imaging to detect "classical EP" and "possible EP." The classical EP was classified into type A (hyperintense excrescence (cyst-like component) on the dorsal surface of the clivus) and type B (hyperintense excrescence plus a hyperintense lesion within the clivus). Possible EP was subdivided as incomplete EP (T2-hypointense protrusion of the clivus) and EP variant (hyperintense lesion within the clivus alone). RESULTS: We found 31 (31 of 399, 7.7 %) EPs of which 11 were defined as classical EP (2.7 %) and 20 were defined as possible EP (5.0 %). Of the 11 classical EPs, 7 (63.6 %) were diagnosed as type A and 4 (% 36.4) were diagnosed as type B. Of the 20 possible EPs, 19 were classified as incomplete EP (95.0 %) and one was classified as EP variant (5.0 %). CONCLUSIONS: Contrast-enhanced FIESTA images are helpful in the assessment of EP, although we do not define a role in the current classification proposed by Chihara et al. (Eur Radiol 23:2854-2860, 2013).

Differential effects of leptin on adiponectin expression with weight gain versus obesity.

BACKGROUND/OBJECTIVE: Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. METHODS/RESULTS: Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8 weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8±1.2 kg resulted in increased adiponectin level (P=0.03), whereas weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (P=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, whereas a leptin antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal-weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in the adipose tissue from normal-weight participants, but did not do so in the adipose tissue from obese participants. Second, we noted that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. CONCLUSIONS: Modest weight gain in healthy individuals is associated with increases in adiponectin levels, which correlate positively with changes in leptin. In vitro, leptin induces adiponectin expression, which is attenuated by increased caveolin-1 expression. In addition, the adipose tissue from obese subjects shows increased caveolin-1 expression and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin levels in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

Motor and cognitive delay in Duchenne muscular dystrophy: implication for early diagnosis.

OBJECTIVES: To examine the relationship between delay in the age of first independent walking and cognitive impairment in boys with Duchenne muscular dystrophy (DMD) to assess how age of diagnosis might be improved. STUDY DESIGN: We reviewed the records of 179 boys with DMD evaluated by the senior author between 1989 and June 2012. Delay in walking was defined as occurring at or greater than 16 months of age. Cognitive impairment was identified by school placement in special education or lower than expected grade level during the elementary school years. RESULTS: Delay in walking and cognitive impairment are highly correlated (P ≤ .0001). If cognitively delayed, boys with DMD were 3 times more likely to have a delay in walking. This association was shown to be independent from the rate of motor degeneration (P = .9) and the age of diagnosis (P = .6, combined average = 5.1 ± 2 years). CONCLUSION: Delay in the onset of walking in boys with DMD is strongly associated with cognitive delay. We suspect that primary care givers overlook DMD as a possible cause of delay in the age of independent walking when early features of cognitive delay are also apparent. DMD should be included among those disorders causing global developmental delay. Recognition of this association could substantially decrease the age of diagnosis for many boys with DMD. We suggest that the standard evaluation for boys with global developmental delay include an inexpensive and sensitive serum creatine kinase test.

Neurogenous hyperplasia in the oesophagus.

Leiomyoma and gastrointestinal stromal tumours take first place among mesenchymal tumours of the oesophagus, where tumours of peripheral nerve origin are rarely seen. Schwann and enterochromaffi n cell proliferation occur in neurogenous hyperplasia, an entity observed in the appendix which has not been reported in the oesophagus in the medical literature. Oesophagogastroscopy of a 58-year-old woman showed linear erosions and nodularity at the gastroesophageal junction. The microscopic examination of biopsies taken from this area revealed proliferation of spindle cells with oval-round nuclei forming focal fascicular arrangement in the lamina propria. These cells stained positive for synaptophysin and S100-protein, while immunohistochemistry for smooth muscle actin and CD117 were negative. The case was diagnosed as neurogenous hyperplasia with these findings. Control endoscopic biopsies showed no evidence of neurogenous hyperplasia. Neurogenous hyperplasia can be considered as a distinct entity which might also be observed in the oesophagus as in the appendix.

The value of FDG-PET/CT in the post-treatment evaluation of endometrial carcinoma: a comparison of PET/CT findings with conventional imaging and CA 125 as a tumour marker.

OBJECTIVES: This retrospective study was designed to assess the value of positron emission tomography/computed tomography imaging (PET/CT) in the post-treatment evaluation of the patients with endometrial carcinoma and to compare PET/CT scan with conventional imaging (CI) including computed tomography (CT), ultrasonography (US) and magnetic resonance imaging (MRI) and CA 125 with both 20U/ml and 35U/ml cut-off values. MATERIALS AND METHODS: A total of 31 patients who were treated for histopathologically proven endometrial adenocarcinoma, underwent PET/CT examination for restaging and suspected recurrence. Thirty five PET/CT studies were performed in 31 patients. Lesion status was determined on the basis of clinical follow-up including radiological imaging (follow-up CT scan) at least 6 months and response to therapy. RESULTS: Of the 35 PET/CT studies, 13 (37%) studies were positive, whereas 22 (63%) of them were negative. On study-based analysis the overall sensitivity, specificity, accuracy for PET/CT imaging were 100%, 96% and 97%, respectively. The corresponding information for CI were 46%, 87% and 74%, for CA 125 (cut off=20U/ml) measurement were 45%, 88% and 74%, and for CA 125 (cut off=35U/ml) measurement were 27%, 100% and 78%, respectively. On lesion-based analysis, PET/CT revealed only one false positive case. In none of 21 patients with negative 22 PET/CT studies, no subsequent clinical or radiological recurrences were observed with a follow-up of at least 6 months. CONCLUSION: FDG-PET/CT is found more useful modality than CI and CA 125 in the evaluation of post-treatment endometrial carcinoma patients, for suspected recurrence.

Splenic and multiple abdominal metastases of endometrial carcinoma detected with FDG-PET/CT.

A 58 year old female was referred for FDG-PET/CT for restaging of endometrial adenocarcinoma. For evaluation of treatment, no metastases were detected on FDG-PET/CT which was performed 18 months later after the surgery. During follow-up, FDG-PET/CT was performed 6 months later than the previous FDG-PET/CT for restaging. A lesion with increased metabolic activity (SUV max: 10.21) was detected at spleen which was not seen on previous FDG-PET/CT scan. The lesion was consistent with metastasis of endometrial carcinoma. Splenic metastasis of endometrial carcinoma is extremely rare. There are only 13 cases of splenic metastasis from endometrial carcinoma that reported in the literature before. There is only one splenic metastasis of endometrial carcinoma case reported in the literature which is imaged with FDG-PET. To best of our knowledge this is the first report of solitary splenic metastasis of endometrial carcinoma that is imaged with FDG-PET/CT.

Primary epithelioid trophoblastic tumor with a synchronous breast carcinoma detected only with FDG-PET/CT Scan.

Epithelioid trophoblastic tumor is a recently described, rare and distinctive type of gestational trophoblastic tumor. We report the case of a 31-year old patient who had a full-term pregnancy 18 months before presentation. She had a right axillary lymph node metastasis and was referred for FDG-PET/CT scan for evaluation of distant metastasis and to detect primary malignancy. The axillary lymph node biopsy revealed metastatic breast carcinoma. FDG-PET/CT revealed increased uptake of right axillary lymph node, soft tissue density lesion with a diameter of 24 mm on left cervical region with increased FDG uptake, increased uptake on cervical region and left inguinal lymph node with increased uptake. Pelvic MRI imaging and ultrasonography were negative for malignancy in cervical region. Biopsy of the lesion was consistent with epithelioid trophoblastic tumor in cervical region. Gestational trophoblastic tumor was not suspected because she had no signs such as abnormal vaginal bleeding. FDG-PET/CT demonstrated the primary lesion in cervical region. We report a rare case of primary epithelioid trophoblastic tumor detected only with FDG-PET/CT scan which synchronized with breast carcinoma.

Comparison of bone scintigraphy and 18F-FDG PET-CT in a prostate cancer patient with osteolytic bone metastases.

A 62 year-old male with prostate cancer, recently complaining lumbar pain with elevated PSA level (6.83 ng/ml) was referred for evaluating bone metastases. Bone scintigraphy with (99m)Tc-MDP demonstrated intense uptake on third lumbar vertebra. Postoperative biopsy of the lesion on third lumbar vertebra revealed adenocarcinoma metastasis. For evaluating distant metastases and restaging, (18)F-FDG PET-CT was performed postoperatively. On PET-CT imaging there were cervical and left parailiac lymph nodes with FDG uptake, destruction on third lumbar vertebra level and intense soft tissue mass FDG uptake on the same area. Additionally, FDG uptake was detected on right iliac crest. On the CT images obtained by integrated PET-CT scanner, this uptake was matching with lytic bone metastases. The superiority of (18)F-FDG PET-CT for demonstrating osteolytic bone metastases compared to bone scintigraphy was presented in a case of prostate cancer in a patient with bone and lymph node metastases.