Identification of preoperative factors associated with outcomes following surgical management of intra-abdominal recurrent or metastatic GIST following neoadjuvant tyrosine kinase inhibitor therapy.

BACKGROUND: The role of surgical resection in the treatment of patients with metastatic/recurrent gastrointestinal stromal tumors (GIST) is unclear. The aim of this study was to identify preoperative factors associated with oncologic outcomes for recurrent/metastatic GIST after tyrosine kinase inhibitor (TKI) therapy. METHODS: We identified 107 patients with metastatic or recurrent GIST treated with TKIs and surgical resection (2002-2012). Patients that underwent palliative or incomplete resection were excluded. Complete resection was achieved in 87 patients which comprise the analytic cohort. Univariate and multivariate analyses were conducted to identify risk factors for GIST-specific survival (DSS) and time-to-recurrence (TTR). RESULTS: At a median follow-up of 51 months (91 months for survivors), median DSS was 74 months and TTR was 21 months. By univariate analysis, unifocal disease, duration of TKI < 365 days, and no evidence of radiographic progression were associated with improved TTR and DSS. Multivariate Cox regression demonstrated that evidence of radiographic progression was associated with shorter DSS (HR 2.53, 95%CI = 1.27-5.06, P = 0.008) and increased risk of recurrence (HR 3.33, 95%CI = 1.91-5.82, P < 0.001). CONCLUSIONS: Patients with unifocal disease and radiographic evidence of response to TKI therapy may achieve improved oncologic outcomes when complete surgical resection is achieved following treatment with TKI.

Interaction of primary human trabecular meshwork cells with metal alloy candidates for microinvasive glaucoma surgery.

BACKGROUND: Microinvasive glaucoma surgery (MIGS) is a relatively new addition to the glaucoma treatment paradigm. Small metallic stents are inserted into the trabecular meshwork in order to increase aqueous humour drainage. MIGS procedures are rapidly being adopted owing to a more favourable side effect profile when compared with traditional surgery. Remarkably, this rapid rate of utilization has occurred without any published studies on the effect of metal alloys used in these stents on human trabecular meshwork cells (HTMCs). Therefore, this study aimed to determine the effect of candidate metal alloys for MIGS on HTMC morphology, viability and function. METHODS: Human trabecular meshwork cells were cultured on the surfaces of titanium (polished and sandblasted), a titanium-nickel (nitinol) alloy and glass (as control substratum). Fluorescence imaging was used to assess cell morphology and spreading. A lactate dehydrogenase cytotoxicity assay, cell death detection ELISA, MTT cell viability assay, BrdU cell proliferation assay and fibronectin ELISA were also conducted. RESULTS: Cells cultured on sandblasted titanium exhibited significantly greater spreading than cells cultured on other substrata. In comparison, HTMCs cultured on nitinol displayed poor spreading. Significantly more cell death, by both necrosis and apoptosis, occurred on nitinol than on titanium and glass. Also, cell viability and proliferation were suppressed on nitinol compared with titanium or glass. Finally, HTMCs on both titanium and nitinol produced greater amounts of fibronectin than cells grown on glass. CONCLUSIONS: Substratum topography and metal alloy composition were found to impact morphology, viability and function of primary HTMC cultures.

Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and sporadic cases. Furthermore, both SUZ12 and EED mutations in MPNSTs were associated with loss of H3K27 tri-methylation, a downstream target of PRC2. Therefore, we tested whether H3K27me3 immunohistochemistry is useful as a diagnostic and prognostic marker for MPNSTs. We performed H3K27me3 immunohistochemistry in 162 primary MPNSTs, 97 neurofibromas and 341 other tumors using tissue microarray. We observed loss of H3K27me3 in 34% (55/162) of all MPNSTs while expression was retained in all neurofibromas including atypical (n=8) and plexiform subtypes (n=24). Within other tumors we detected loss of H3K27me3 in only 7% (24/341). Surprisingly, 60% (9/15) of synovial sarcomas and 38% (3/8) of fibrosarcomatous dermatofibrosarcoma protuberans (DFSP) showed loss of H3K27 trimethylation. Only 1 out of 44 schwannomas showed loss of H3K27me3 and all 4 perineuriomas showed intact H3K27me3. Furthermore, MPNSTs with loss of H3K27 tri-methylation showed inferior survival compared with MPNSTs with intact H3K27 tri-methylation, which was validated in two independent cohorts. Our results indicate that H3K27me3 immunohistochemistry is useful as a diagnostic marker, in which loss of H3K27me3 favors MPNST above neurofibroma. However, H3K27me3 immunohistochemistry is not suitable to distinguish MPNST from its morphological mimicker synovial sarcoma or fibrosarcomatous DFSP. Since loss of H3K27 tri-methylation was related to poorer survival in MPNST, chromatin modification mediated by this specific histone seems to orchestrate more aggressive tumour biology.

Sarcoma Brain Metastases: 28 Years of Experience at a Single Institution.

BACKGROUND: Brain metastasis from sarcoma is rare, thus limited information is available. We examined sarcoma brain metastases diagnosed at our institution over a period of 28 years. METHODS: This is a retrospective study of 112 cases. Clinical records were reviewed and clinical, pathological, and survival data were tabulated. RESULTS: Undifferentiated sarcoma was the most common source. In 50 % of cases, the primary sarcoma was in the extremities. Most patients were adults at the time of first brain metastasis, and median age was 34.8 years. Although most patients evidenced metastatic disease to other sites prior to developing brain metastasis, in almost one quarter, brain was the initial site. Most of the metastatic foci were parenchymal, nonhemorrhagic, and solitary. Forty percent of the brain metastatic deposits were located in the frontal lobes. Thirty-one percent recurred-all within 5.3 years. Seventy-six percent of patients succumbed to the disease, with a median survival time of only 0.6 years. Hemorrhagic metastatic foci were found to be associated with significantly lower recurrence-free, as well as disease-specific survivals. No difference in survival was noted between single versus multiple deposits or primary soft tissue versus bone sarcomas. No statistically significant effect on survival was found when neurosurgical resection was combined with radiotherapy. Chemotherapy, on the other hand, was found to significantly improve disease-specific survival when combined with metastasectomy. CONCLUSIONS: Undifferentiated sarcoma was the most common source of brain metastasis. Most cases showed evidence of prior metastatic disease. Surgical resection is employed to manage symptoms, but prognosis remains dismal.

Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma.

BACKGROUND: Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The purpose of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes. METHODS: A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA, and outcome. RESULTS: At a median follow-up of 3.9 years (9 years for survivors), 5-year disease-specific survival (DSS) was 63 %. Clinical variables associated with improved DSS included age <61 years, tumor size <10 cm, margin-negative resection, and sporadic-tumor status. At the protein level, loss of cyclin D1 (p = 0.06), pEGFR (p = 0.023), pIGF-1R (p = 0.022), and PTEN (p < 0.001) and overexpression of AXL (p = 0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA, and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS), whereas RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R. DISCUSSION: Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA-UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions.

Progressive loss of myogenic differentiation in leiomyosarcoma has prognostic value.

AIMS: Well-differentiated leiomyosarcomas show morphologically recognizable smooth muscle differentiation, whereas poorly differentiated tumours may form a spectrum with a subset of undifferentiated pleomorphic sarcomas. The expression of certain muscle markers has been reported to have prognostic impact. We investigated the correlation between the morphological spectrum and the muscle marker expression profile of leiomyosarcoma, and the impact of these factors on patient outcomes. METHODS AND RESULTS: Tissue microarrays including 202 non-uterine and 181 uterine leiomyosarcomas with a spectrum of tumour morphologies were evaluated for expression of immunohistochemical markers of muscle differentiation. Poorly differentiated tumours frequently lost one or more conventional smooth muscle markers [smooth muscle actin, desmin, h-caldesmon, and smooth muscle myosin (P < 0.0001)], as well as the more recently described markers SLMAP, MYLK, and ACTG2 (P < 0.0001). In primary tumours, both desmin and CFL2 expression predicted improved overall survival in multivariate analyses (P = 0.0111 and P = 0.043, respectively). Patients with muscle marker-enriched tumours (expressing all four conventional markers or any three of ACTG2, CFL2, CASQ2, MYLK, and SLMAP) had improved overall survival (P < 0.05) in univariate analyses. CONCLUSIONS: Morphologically and immunohistochemically, poorly differentiated leiomyosarcomas can masquerade as undifferentiated pleomorphic sarcomas with progressive loss of muscle markers. The expression of muscle markers has prognostic significance in primary leiomyosarcomas independently of tumour morphology.

Decomposition analysis of racial and ethnic differences in receipt of immediate postpartum, long-acting, reversible, and permanent contraception.

OBJECTIVES: This study aimed to determine the factors contributing to racial and ethnic disparities in the use of immediate postpartum, long-acting reversible contraception (IPP LARC) and permanent contraception among Medicaid recipients. STUDY DESIGN: We conducted a cross-sectional study using 3 years of national Medicaid claims data to examine the rates of IPP LARC use alone and a composite measure of postpartum permanent contraception and IPP LARC within 7 days of delivery by race and ethnicity. We used a Blinder-Oaxaca model to quantify the extent to which medical complexity, age, rurality, mode of delivery, and year explained differences in outcomes among different minoritized groups in comparison to non-Hispanic White women. RESULTS: Our study sample contained 1,729,663 deliveries occurring from 2016 through 2018 among 1,605,199 people living in 16 states. IPP LARC use rates were highest among Black (2.2%), followed by American Indian and Alaska Native at 2.1% and Hawaiian/Pacific Islander beneficiaries at 1.9%, Hispanic (all races) at 1.2%, and Asian at 1.0%. IPP LARC was lowest among White beneficiaries (0.8%). Medical complexity, age, rurality, year, and mode of delivery explained only 12.3% of the difference in IPP LARC rates between Black and White beneficiaries. Postpartum permanent contraception was highest among White (7.6%), Hispanic (7.2%), and American Indian and Alaska Native (6.8%), followed by Black (6.3%), Hawaiian/Pacific Islander (5.1%) and lowest among Asian women (4.1%). When we examined the use of IPP LARC or postpartum permanent contraception together, these same factors explained 94.4% of the differences between Black and White beneficiaries. CONCLUSIONS: While differences in the use of IPP LARC by race and ethnicity were identified, our findings suggest that overall use of inpatient highly effective contraception are similar across racial and ethnic groups. IMPLICATIONS: When IPP LARC and postpartum permanent contraception are examined jointly, their use is similar across racial and ethnic groups.

Medicaid Policy Change and Immediate Postpartum Long-Acting Reversible Contraception.

Importance: Improving access to the choice of postpartum contraceptive methods is a national public health priority, and the need is particularly acute within the Medicaid population. One strategy to ensure individuals have access to the full range of contraceptive methods is the provision of a method prior to hospital discharge following a birth episode. Beginning in 2016, some states changed their Medicaid billing policy, allowing separate reimbursement for intrauterine devices and contraceptive implants to increase the provision of long-acting reversible contraceptive (LARC) methods immediately postpartum (IPP). Objective: To assess the association of a change in Medicaid billing policy with use of IPP LARC. Design, Setting, and Participants: The cohort study of postpartum Medicaid recipients in 9 treatment and 6 comparison states was conducted from January 2016 to October 2019. Data were analyzed from August 2023 to January 2024. Main Outcomes and Measures: The primary outcome was use of IPP LARC. Results: The final sample included 1 378 885 delivery encounters for 1 197 287 Medicaid enrollees occurring in 15 states. Mean age of beneficiaries at delivery was 27 years. The IPP LARC billing policy was associated with a mean increase of 0.74 percentage points (95% CI, 0.30-1.18 percentage points) in the immediate receipt of IPP LARC, with a prepolicy baseline rate of 0.54%. The IPP LARC billing policy was also associated with an overall increase of 1.48 percentage points (95% CI, 0.43-2.73 percentage points) in LARC use by 60 days post partum. Conclusions and Relevance: In this cohort study, changing Medicaid billing policy to allow for separate reimbursement of LARC devices from the global fee was associated with increased use of IPP LARC, suggesting that this may be a strategy to improve access to the full range of postpartum contraceptive methods.

Twelve-Month Contraceptive Supply Policies and Medicaid Contraceptive Dispensing.

Importance: Nineteen states have passed legislation requiring insurers to cover the dispensation of a 12-month supply of short-acting, hormonal contraception. Objective: To determine whether 12-month contraceptive supply policies were associated with an increase in the receipt of 12-month or longer supply of contraception. Design, Setting, and Participants: This retrospective cohort study included data from all female Medicaid enrollees aged 18 to 44 years who used short-acting hormonal contraception (ie, pill, patch, or ring) from 2016 to 2020. Exposures: Eleven treatment states where legislation required insurers to cover a 12-month supply of contraception to continuing users and 25 comparison states without such legislation prior to December 2020. Main Outcomes and Measures: Proportion of contraception months received via a single 12-month or longer fill. Results: This study included 48 255 512 months of dispensed oral pill, patch, and ring contraception prescription supply among 4 778 264 female Medicaid enrollees. The majority of months of supplied contraception were for the contraceptive pill rather than the patch or ring. In a staggered difference-in-differences model, the 12-month supply policy was associated with an estimated 4.39-percentage point (pp) increase (95% CI, 4.38 pp-4.40 pp) in the proportion of contraception dispensed as part of a 12-month or longer supply, from a mean of 0.11% in treatment states during the first quarter of the study period. Investigating the heterogeneity in policy association across states, California stood out with a 7.17-pp increase (95% CI, 7.15 pp-7.19 pp) in the proportion of contraception dispensed as a 12-month or longer supply; in the other 10 treatment states, the policy association was less than 1 pp. Conclusions and Relevance: In this cohort study of Medicaid recipients using short-acting hormonal contraception, the passage of a 12-month contraceptive supply policy was associated with a minimal increase in the proportion of contraception dispensed through a 12-month or longer supply.

Geographical Variations In Emergency Department Visits For Mental Health Conditions For Medicaid Beneficiaries.

Despite Medicaid's importance as a payer and source of coverage for mental health care, relatively little is known about how prevalence, access, and quality might vary among Medicaid beneficiaries. This study used national Medicaid data from 2018 to assess regional variations in emergency department (ED) visits for mental health conditions, a measure that may reflect unmet needs for behavioral health care. We found substantial variations, with rates in the region with the highest visit rates eight times higher than those in the region with the lowest rates. Many regions with high rates of ED visits for mental health conditions also had high rates of outpatient mental health use. Regional patterns differed substantially, with some regions exhibiting high rates of ED visits related to anxiety but low rates for schizophrenia and vice versa. The presence of large variations in ED visits for mental health conditions, with substantial differences in the composition across regions, suggests a need for context-specific solutions, including assessments of the ways in which mental health benefits are structured at the state Medicaid agency level and of differences in provider accessibility and an understanding of the types of mental illness underlying high rates of use.

Catholic sole community hospitals are associated with decreased receipt of postpartum permanent contraception among Medicaid recipients.

OBJECTIVES: To examine the association of Catholic hospitals with receipt of postpartum tubal ligation and long acting, reversible contraception among Medicaid recipients. STUDY DESIGN: We conducted a retrospective cohort study of live births from January 1, 2016 to October 31, 2016 to female Medicaid beneficiaries in the United States between ages 21 and 44. Our main exposure was the presence of a Catholic-affiliated sole community hospital, and our primary outcome was highly effective postpartum contraception. We examined rates of postpartum permanent contraception, along with the use of a long acting, reversible form of contraception (LARC) at 3 and 60 days are postpartum. We compared counties that had only a Catholic-affiliated hospital with counties with only a non-Catholic hospital. RESULTS: Our study population included 14,545 postpartum Medicaid beneficiaries. Study participants came from 88 counties across 10 United States states. Only 7.7% of women in counties with Catholic sole community hospitals received permanent contraception by 3 days postpartum, compared to 11.3% in counties with non-Catholic sole community hospitals (RD: -3.92%; 95% CI: -6.01%, -1.83%). This difference was not mitigated by receipt of outpatient procedures or long-acting, reversible contraception. Importantly, women residing in counties with Catholic sole community hospitals were much less likely to return postpartum for an outpatient visit between 8 and 60 days postpartum than women in counties with non-Catholic sole community hospitals (35.4% vs 45.4%, RD: -9.29%; 95% CI: -16.71%, -1.86%). CONCLUSIONS: In counties where the only hospital was Catholic, Medicaid recipients giving birth were significantly less likely to receive permanent contraception and to return for postpartum care. IMPLICATIONS: Catholic hospitals are increasing in the United States, which may restrict access to postpartum contraception, particularly in rural areas. We found that Medicaid recipients giving birth at a Catholic sole community hospital were less likely to receive permanent contraception and to return for care.

Medicaid Reimbursement For Psychiatric Services: Comparisons Across States And With Medicare.

Medicaid is characterized by low rates of provider participation, often attributed to reimbursement rates below those of commercial insurance or Medicare. Understanding the extent to which Medicaid reimbursement for mental health services varies across states may help illuminate one lever for increasing Medicaid participation among psychiatrists. We used publicly available Medicaid fee-for-service schedules from state Medicaid agency websites in 2022 to construct two indices for a common set of mental health services provided by psychiatrists: a Medicaid-to-Medicare index to benchmark each state's Medicaid reimbursement with that of Medicare for the same set of services, and a state-to-national Medicaid index comparing each state's Medicaid reimbursement with an enrollment-weighted national average. On average, Medicaid paid psychiatrists at 81.0 percent of Medicare rates, and a majority of states had a Medicaid-to-Medicare index that was less than 1.0 (median, 0.76). State-to-national Medicaid indices for psychiatrists' mental health services ranged from 0.46 (Pennsylvania) to 2.34 (Nebraska) but did not correlate with the supply of Medicaid-participating psychiatrists. As policy makers look to reimbursement rates as one strategy to address ongoing mental health workforce shortages, comparing Medicaid payment across states may help benchmark ongoing state and federal proposals.

The association of federal Medicaid abortion funding restrictions with adverse obstetric outcomes among United States Medicaid recipients.

OBJECTIVE: We examine the association of the Hyde Amendment with obstetrical outcomes in a national Medicaid population. STUDY DESIGN: We conducted a national study of Medicaid-funded abortions to determine the association of restrictions on adolescent, preterm, low-birth weight, and short interpregnancy interval births using administrative data. RESULTS: States that restricted coverage for abortion had a higher median rate of adolescent (10.2%; vs 7.4%; p-value < 0.001), preterm (11.4%; vs 10.1%; p < 0.001), short interpregnancy interval, (13.0% vs 9.6%; p < 0.001), and low birth weight births (10.2% vs 8.7%; p = 0.003) than states where Medicaid provided comprehensive coverage. CONCLUSIONS: Restricting federal funds for abortion is associated with adverse outcomes. IMPLICATIONS: When Medicaid does not provide comprehensive coverage for abortion care, few abortions are provided and higher rates of adverse obstetrical outcomes are noted.

Geographic Variation In Effective Contraceptive Use Among Medicaid Recipients In 2018.

Medicaid is the largest payer for publicly funded contraception, serving millions of women across the United States. However, relatively little is known about the extent to which effective contraceptive services vary geographically for Medicaid recipients. This study used national Medicaid claims to assess county-level variation in rates of provision of the most or moderately effective methods of contraception and provision of long-acting reversible contraception (LARC) across forty states and Washington, D.C., in 2018. County-level rates of most or moderately effective contraceptive use varied almost fourfold across states, from a low of 10.8 percent to a high of 44.4 percent. Rates of LARC provision varied almost tenfold, from a low of 1.0 percent to a high of 9.6 percent. Despite the fact that contraception is a core benefit within Medicaid, access and use vary substantially across and within states. Medicaid agencies have a variety of options to ensure that people have access to a choice of the full range of contraceptive methods, including removing or loosening utilization controls, incorporating quality metrics or value-based payments into contraceptive services, and adjusting reimbursement to remove barriers to the clinical provision of LARC.

P3a amplitude to trauma-related stimuli reduced after successful trauma-focused PTSD treatment.

An elevated P3a amplitude to trauma-related stimuli is strongly associated with posttraumatic stress disorder (PTSD), yet little is known about whether this response to trauma-related stimuli is affected by treatment that decreases PTSD symptoms. As an analysis of secondary outcome measures from a randomized controlled trial, we investigated the latency and amplitude changes of the P3a in responses in a three-condition oddball visual task that included trauma-related (combat scenes) and trauma-unrelated (threatening animals) distractors. Fifty-five U.S. veterans diagnosed with combat-related PTSD were randomized to receive either active or sham repetitive transcranial magnetic stimulation (rTMS). All received cognitive processing therapy, CPT+A, which requires a written account of the index trauma. They were tested before and 6 months after protocol completion. P3a amplitude and response time decreases were driven largely by the changes in the responses to the trauma-related stimuli, and this decrease correlated to the decrease in PTSD symptoms. The amplitude changes were greater in those who received rTMS + CPT than in those who received sham rTMS + CPT, suggesting that rTMS plays beneficial role in reducing arousal and threat bias, which may allow for more effective engagement in trauma-focused PTSD treatment.

PET/CT Imaging as a Diagnostic Tool in Distinguishing Well-Differentiated versus Dedifferentiated Liposarcoma.

Distinguishing well-differentiated liposarcoma (WDLPS) from dedifferentiated liposarcoma (DDLPS) is essential given distinct treatment paradigms and chemosensitivity. Percutaneous biopsy has a low sensitivity for detecting DDLPS. We sought to identify the diagnostic utility of positron emission tomography/computed tomography (PET/CT) in identifying WDLPS versus DDLPS. An independent radiologist reviewed PET/CT images to identify target lesions and determine the maximum standardized uptake value (SUVmax). An independent pathologist review confirmed WDLPS or DDLPS histology. A binary cutoff point of SUVmax was identified using a classification and regression trees (CART) algorithm. We identified 20 patients with WDLPS or DDLPS with 26 PET/CTs performed for separate recurrences that were followed by surgical sampling. Of the 26 records, 12 were DDLPS (46%) and 14 were WDLPS (54%). Patients with DDLPS had significantly higher SUVmax than those with WDLPS (p value = 0.0035). A SUVmax of 4 was identified as the cutoff point. Using this cutoff, the sensitivity of SUVmax identifying a case as DDLPS was 83.3% (95% CI: 51.6%, 97.9%) and the specificity was 85.7% (95% CI: 57.2%, 98.2%). PET/CT is a sensitive and specific diagnostic tool to identify the presence of dedifferentiation within the tumor.

Social representations of chronic pain in newspapers, online media, and film.

Social representation theory provides a framework for studying how scientific knowledge affects common sense and communication through inquiries into everyday discourse. This qualitative study examined social representations of chronic pain from 4 sources: North American newspapers; "Chronic Illness Cat" memes from the social media web site, Pinterest; video blogs on YouTube; and from a 2014 film, Cake, and interviews and comments concerning it. Using thematic analysis, we first identified social representations found in our 4 sources and others found in 1 or 2 of them. Second, we analyzed the sources for their rhetorical intentions. Vlogs directly and memes indirectly were first-person accounts, self-authorizing statements of the truth of chronic pain, whereas newspaper articles and the film were third-person accounts of pain, the differences between these perspectives affecting what was said. We conclude that the medium shapes the message.