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.

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.

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.

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.

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.

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.

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.

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.

Validity and reliability of an intuitive conscious sedation scoring tool: the nursing instrument for the communication of sedation.

OBJECTIVE: To develop a symmetrical 7-level scale (+3, "dangerously agitated" to -3, "deeply sedated") that is both intuitive and easy to use, the Nursing Instrument for the Communication of Sedation (NICS). DESIGN: Prospective cohort study. SETTING: University medical center. PATIENTS: Mixed surgical, medical intensive care unit (ICU) population. INTERVENTIONS: Patient assessment. MEASUREMENTS AND MAIN RESULTS: Criterion, construct, face validity, and interrater reliability of NICS over time and comparison of ease of use and nursing preference between NICS and four common intensive care unit sedation scales. A total of 395 observations were performed in 104 patients (20 intubated [INT], 84 non intubated) by 59 intensive care unit providers. Criterion validity was tested comparing NICS WITH the 8-point level of arousal scale, demonstrating excellent correlation (rs = .96 overall, .95 non intubated, 0.85 intubated, all p < .001). Construct validity was confirmed by comparing NICS with the Richmond Agitation-Sedation Scale, demonstrating excellent correlation (rs = .98, p < .001). Face validity was determined in a blinded survey of 53 intensive care unit nurses evaluating NICS and four other sedation scales. NICS was highly rated as easy to score, intuitive, and a clinically relevant measure of sedation, and agitation and was preferred overall (74% NICS, 17% Richmond Agitation-Sedation Scale, 11% Other, p < .001 NICS vs. Richmond Agitation-Sedation Scale). Interrater reliability was assessed, using the five scales at three timed intervals, during which 37% of patients received sedative medication. The mean NICS score consistently correlated with each of the other scales over time with an rs of >.9. Using the intraclass correlation coefficient as a measure of Interrater reliability, NICS scored as high, or higher than Richmond Agitation-Sedation Scale, Riker Sedation-Agitation Scale, Motor Activity Assessment Scale, or Ramsay over the three time periods. CONCLUSION: NICS is a valid and reliable sedation scale for use in a mixed population of intensive care unit patients. NICS ranked highest in nursing preference and ease of communication and may thus permit more effective and interactive management of sedation.

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.

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).

Irritable bowel syndrome in young and elderly patients with stable asthma.

BACKGROUND: It has been speculated that asthma and irritable bowel syndrome may share common pathophysiological processes. AIM: To estimate the prevalence of irritable bowel syndrome in young and elderly patients with stable asthma. PATIENTS AND METHODS: Sixty-five young (age < 60 years) and 66 elderly (age > or = 60 years) stable asthmatics, and 119 age-matched healthy volunteers were enrolled. In all participants, presence of irritable bowel syndrome, quality of life and psychological status were evaluated. RESULTS: The prevalence of irritable bowel syndrome in asthmatic group was higher than that in the control group (27.5% versus 16.8%; odds ratio, 1.8 [1.0-3.4]; p=0.04). The prevalence of irritable bowel syndrome was significantly higher in young asthmatics than in age-matched healthy controls (36.9% versus 20.3%; odds ratio, 2.2 [1.0-5.1]; p=0.04) and than in elderly asthmatics (36.9% versus 18.2%; odds ratio, 0.3 [0.1-0.8]; p=0.01). Logistic regression analysis identified the younger age (odds ratio, 2.1 [1.1-3.8]; p=0.01), and the presence of asthma (odds ratio, 1.9 [1.0-3.5]; p=0.03) as independent risk factors for irritable bowel syndrome in all participants after adjusting for gender. We also found impaired quality of life to be associated with the presence of irritable bowel syndrome and asthma in all participants after adjusting for age and gender. CONCLUSION: The prevalence of irritable bowel syndrome appears to be significantly higher in young asthmatics, but not in elderly asthmatics, compared to age-matched healthy counterparts. Potential pathogenic mechanisms of higher irritable bowel syndrome prevalence in young asthmatics need to be explained by further studies.

Maxillary and temporal fibrous dysplasia: three cases.

PROBLEMS/OBJECTIVES: Fibrous dysplasia (FD) is a benign, expansile lesion of bone with slow progression and unknown origin. The purpose of this report is to make physicians aware of the symptoms, methods for differential diagnosis, and treatment options. METHODOLOGY: Three cases of monostotic FD are presented; two involving the maxillary sinus, and one in temporal bone. CT scans are the definitive diagnostic and follow-up method. Surgical approaches to alleviate the symptoms, including facial deformity, are described. RESULTS: FD went undiagnosed for three years in these patients. All three patients were relieved of the symptoms by limited surgery, and remained asymptomatic for up to two years after the surgery, with no signs of recurrence. CONCLUSIONS: Practitioners should be alert to the possibility of FD, particularly if patients develop narrowing of the ear canal, or progressive postauricular or maxillofacial enlargement. Minimal surgery to alleviate the symptoms is the treatment of choice.

Serum and CSF levels of haloperidol by radioimmunoassay and radioreceptor assay during high-dose therapy of resistant schizophrenic patients.

Serum and cerebrospinal fluid (CSF) levels of haloperidol were measured in 12 chronic neuroleptic-nonresponsive schizophrenic patients after 1 month on 60 mg haloperidol daily and then again after 1 month on 120 mg haloperidol daily. Serum haloperidol and CSF haloperidol rose with increasing dose. Serum and CSF levels were significantly correlated. No clinical improvement was achieved despite the high serum and CSF drug levels.

Can dobutamine echocardiography induce myocardial damage in patients with dysfunctional but viable myocardium supplied by a severely stenotic coronary artery?

In animal experiments, dobutamine infusion was found to impair the oxygen supply-demand balance in hypoperfused areas of hibernating myocardium which may induce myocardial damage. The aim of our study was to assess whether dobutamine echocardiography can induce myocardial damage detected by an increase in the cardiac troponin T level in blood. Twenty seven patients with coronary artery disease and severe stenosis of at least one major coronary artery (> or = 90% of luminal diameter narrowing) supplying dysfunctional myocardial segments underwent dobutamine echocardiography. Dobutamine was infused in 3 min dose increments of 5, 10, 20, 30, and 40 microg per kg body weight per minute with the addition of atropine up to 1 mg if ischemia or an 85% predicted maximal heart rate were not achieved. In 15 patients the protocol with prolonged application of 40 microg per kg per minute of dobutamine for 6 min and for the next 5 min with the addition of atropine was used. To exclude minor myocardial damage, an increase in the cardiac troponin T blood level was assessed qualitatively by the TROP T sensitive Rapid Test 20 h after dobutamine echocardiography. In 20 patients the dysfunctional segments were found to be viable with inducible ischemia exhibiting either continuous worsening in systolic thickening or "biphasic" response characterised by the improvement of their systolic thickening with a small dose and by a worsening of the thickening with a high dose of dobutamine. No patient exhibited positive TROP T sensitive Rapid Test result. In patients with coronary artery disease and severe stenosis of a major coronary artery supplying dysfunctional but viable myocardial segments, dobutamine echocardiography does not induce myocardial damage detectable by an increase in cardiac troponin T level.