Embedded Palliative Care for Amyotrophic Lateral Sclerosis: A Pilot Program and Lessons Learned.

Background and Objectives: Palliative care (PC) is recommended for people with amyotrophic lateral sclerosis (ALS), but there is scant literature about how to best provide this care. We describe the structure and impact of a pilot program that integrates longitudinal, interdisciplinary PC into the care of patients with ALS. Methods: Observational cohort study of patients with ALS referred to outpatient PC and seen for at least 3 PC visits October 2017-July 2020. Results: Fifty-five patients met the inclusion criteria. Three-quarters (74.5%) were Caucasian, and 78.2% spoke English. Patients were referred for advance care planning (58.2%), support for patient/family (52.7%), and symptoms other than pain (50.9%). Patients had a mean of 5 scheduled PC visits, the majority occurred by video. A PC physician, nurse, social worker, and chaplain addressed pain (for 43.6% of patients), nonpain symptoms (94.5%), psychosocial distress (78.2%), spiritual concerns (29.1%), care planning (96.4%), and supported family caregivers (96.4%). With PC, the rate of completion of advance directives increased from 16.4% to 36.4% (p = 0.001) and Physician Orders for Life-Sustaining Treatment forms from 10.9% to 63.6% (p < 0.001). Of the 27 patients who died, 77.8% used hospice, typically for more than 30 days. Eleven patients obtained aid-in-dying prescriptions, and 8 took these medications, accounting for 29.6% of the deaths. Discussion: Integrating longitudinal, interdisciplinary PC into the care of patients with ALS is feasible, addresses needs in multiple domains, and is associated with increased rates of advance care planning. Controlled studies are needed to further elucidate the impact of PC on patients with ALS, their families, and clinicians.

Association Between COVID-19 Exposure and Self-reported Compliance With Public Health Guidelines Among Essential Employees at an Institution of Higher Education in the US.

Importance: Detailed analysis of infection rates paired with behavioral and employee-reported risk factors is vital to understanding how transmission of SARS-CoV-2 infection may be exacerbated or mitigated in the workplace. Institutions of higher education are heterogeneous work units that supported continued in-person employment during the COVID-19 pandemic, providing a test site for occupational health evaluation. Objective: To evaluate the association between self-reported protective behaviors and prevalence of SARS-CoV-2 infection among essential in-person employees during the first 6 months of the COVID-19 pandemic in the US. Design, Setting, and Participants: This cross-sectional study was conducted from July 13 to September 2, 2020, at an institution of higher education in Fort Collins, Colorado. Employees 18 years or older without symptoms of COVID-19 who identified as essential in-person workers during the first 6 months of the pandemic were included. Participants completed a survey, and blood and nasal swab samples were collected to assess active SARS-CoV-2 infection via quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and past infection by serologic testing. Exposure: Self-reported practice of protective behaviors against COVID-19 according to public health guidelines provided to employees. Main Outcomes and Measures: Prevalence of current SARS-CoV-2 infection detected by qRT-PCR or previous SARS-CoV-2 infection detected by an IgG SARS-CoV-2 testing platform. The frequency of protective behavior practices and essential workers' concerns regarding contracting COVID-19 and exposing others were measured based on survey responses. Results: Among 508 participants (305 [60.0%] women, 451 [88.8%] non-Hispanic White individuals; mean [SD] age, 41.1 [12.5] years), there were no qRT-PCR positive test results, and only 2 participants (0.4%) had seroreactive IgG antibodies. Handwashing and mask wearing were reported frequently both at work (480 [94.7%] and 496 [97.8%] participants, respectively) and outside work (465 [91.5%] and 481 [94.7%] participants, respectively). Social distancing was reported less frequently at work (403 [79.5%]) than outside work (465 [91.5%]) (P < .001). Participants were more highly motivated to avoid exposures because of concern about spreading the infection to others (419 [83.0%]) than for personal protection (319 [63.2%]) (P < .001). Conclusions and Relevance: In this cross-sectional study of essential workers at an institution of higher education, when employees reported compliance with public health practices both at and outside work, they were able to operate safely in their work environment during the COVID-19 pandemic.

Breast conservation therapy versus mastectomy in the surgical management of invasive lobular carcinoma measuring 4 cm or greater.

BACKGROUND: The safety of breast conservation therapy (BCT) has not been demonstrated in large ILC tumors, potentially contributing to the higher mastectomy rates seen in ILC. METHODS: We queried a prospectively maintained database to identify patients with ILC measuring ≥4 cm and evaluated difference in recurrence free survival (RFS) between those treated with BCT versus mastectomy using a multivariate model. RESULTS: Of 180 patients, 30 (16.7%) underwent BCT and 150 (83.3%) underwent mastectomy. Patients undergoing mastectomy were younger (56.6 vs. 64.3 years, p = 0.003) and had larger tumors (7.2 vs. 5.4 cm, p < 0.001). While tumor size, nodal stage, receptor subtype, and margin status were significantly associated with RFS, there was no difference in RFS at 5 (p = 0.88) or 10 (p = 0.65) years for individuals undergoing BCT versus mastectomy. CONCLUSIONS: For patients with ILC ≥4 cm, BCT provides similar tumor control as mastectomy, provided that negative margins are achieved.

Evaluating the impact of axillary dissection on recurrence-free survival by extent of nodal disease in invasive lobular carcinoma of the breast.

PURPOSE: Clinical trials have shown that axillary lymph node dissection (ALND) can be avoided for many breast cancer patients with limited nodal involvement. However, whether its omission is safe for those with invasive lobular carcinoma (ILC) is still questioned. We sought to evaluate the impact of ALND on recurrence-free survival (RFS) by extent of nodal disease in patients with ILC. METHODS: We performed a retrospective, cross-sectional analysis of ILC patients treated between 1990 and 2019 at our institution. Patients underwent either breast conservation surgery (BCS) or mastectomy. We used univariate and multivariate statistics in Stata 14.2 to evaluate associations between extent of axillary surgery and time to recurrence stratified by nodal burden. RESULTS: Of 520 cases, 387 (78.4%) were node negative, 74 (14.9%) had 1-2 positive nodes, and 59 (11.4%) had three or more positive nodes. Most patients (93.3%) had hormone receptor-positive disease, and 94.8% had low or intermediate-grade tumors. The rate of ALND significantly decreased over time (p < 0.002). Using a multivariate model, there was no significant difference in RFS estimates based on receipt of ALND (HR = 0.53, 95% CI 0.17-1.64, p = 0.27), which also held true for patients with 1-2 positive nodes using a test of interaction (HR = 0.91, 95% CI 0.12-6.76, p = 0.92). CONCLUSIONS: These findings support the safety of omitting ALND in selected patients with ILC. Further studies of axillary management in ILC and imaging tools to predict nodal involvement and therapeutic response are warranted.

Mitotic score and pleomorphic histology in invasive lobular carcinoma of the breast: impact on disease-free survival.

PURPOSE: Pleomorphic invasive lobular carcinoma (ILC) has long been thought to have worse outcomes than classic ILC and is therefore often treated with chemotherapy. However, recent data question the utility of the pleomorphic designation, as the poor outcomes seen may be related to other associated high-risk features. Importantly, mitotic count may better define a subset of ILC with high risk of recurrence. We sought to determine the impact of pleomorphic histology versus mitotic count on disease-free survival (DFS) in pure ILC. Additionally, we evaluated whether pleomorphic histology was associated with receipt of chemotherapy when adjusting for other factors. METHODS: We analyzed a cohort of 475 patients with stage I-III pure ILC. We used Kaplan-Meier estimates, and Cox proportional hazards and logistic regression for multivariate analyses. Pleomorphic histology was confirmed by central pathology review. RESULTS: In a multivariate model, pleomorphic histology was not associated with reduced DFS. Only mitotic score, receptor subtype, and pathologic stage were independently and significantly associated with DFS. Patients with pleomorphic ILC were significantly more likely to receive chemotherapy than patients with classic ILC (adjusted odds ratio 2.96, p = 0.026). CONCLUSIONS: The pleomorphic designation in ILC does not have clinical utility and should not be used to determine therapy. Rather, mitotic count identified clear prognostic groups in this cohort of pure ILC.

Success rates of re-excision after positive margins for invasive lobular carcinoma of the breast.

Rates of positive margins after surgical resection of invasive lobular carcinoma (ILC) are high (ranging from 18 to 60%), yet the efficacy of re-excision lumpReceptor subtypeectomy for clearing positive margins is unknown. Concerns about the diffuse nature of ILC may drive increased rates of completion mastectomy to treat positive margins, thus lowering breast conservation rates. We therefore determined the success rate of re-excision lumpectomy in women with ILC and positive margins after surgical resection. We identified 314 cases of stage I-III ILC treated with breast conserving surgery (BCS) at the University of California, San Francisco. Surgical procedures, pathology reports, and outcomes were analyzed using univariate and multivariate statistics and Cox-proportional hazards models. We evaluated outcomes before and after the year 2014, when new margin management consensus guidelines were published. Positive initial margins occurred in 118 (37.6%) cases. Of these, 62 (52.5%) underwent re-excision lumpectomy, which cleared the margin in 74.2%. On multivariate analysis, node negativity was significantly associated with successful re-excision (odds ratio [OR] 3.99, 95% CI 1.15-13.81, p = 0.029). After 2014, we saw fewer initial positive margins (42.7% versus 25.5%, p = 0.009), second surgeries (54.6% versus 20.2%, p < 0.001), and completion mastectomies (27.7% versus 4.5%, p < 0.001). In this large cohort of women with ILC, re-excision lumpectomy was highly successful at clearing positive margins. Additionally, positive margins and completion mastectomy rates significantly decreased over time. These findings highlight improvements in management of ILC, and suggest that completion mastectomy may not be required for those with positive margins after initial BCS.

Breast Conservation and Negative Margins in Invasive Lobular Carcinoma: The Impact of Oncoplastic Surgery and Shave Margins in 358 Patients.

BACKGROUND: Invasive lobular carcinoma (ILC) of the breast grows in a diffuse pattern, making complete surgical excision difficult. This results in high rates of positive margins and low rates of successful breast-conserving surgery. We hypothesized that utilizing oncoplastic surgical techniques and selective shave margins would be associated with lower positive margin rates and increased breast conservation in women with ILC. METHODS: We performed a retrospective cross-sectional analysis in a large cohort of prospectively collected ILC cases who received surgical treatment at the University of California, San Francisco, between 1992 and 2017. We identified all patients with histologically proven, unilateral or bilateral, stage 1-3 ILC. The primary outcome was positive margin rates, defined as no ink on tumor. RESULTS: We identified 365 tumors in 358 women, with an average age of 61 years, who underwent breast-conserving surgery, and found that the use of oncoplastic techniques (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.21-0.79, p = 0.008) and the selective use of shave margins (OR 0.393, 95% CI 0.22-0.7, p = 0.002) were significantly associated with lower positive margin rates, when adjusted for tumor size and multifocality. The success rate for breast-conservation surgery was 75%, with a 25% conversion rate to mastectomy. CONCLUSIONS: Surgeons should consider routine use of oncoplastic techniques and shave margins when performing breast-conservation surgery for women with ILC as these methods are associated with significantly lower odds of having positive margins and higher breast-conservation rates.

Decreased physiologic variability as a generalized response to human endotoxemia.

OBJECTIVE: To test the effect in normal human volunteers of transient systemic inflammation on the variability in time-series behaviors of widely divergent physiologic measures of the human inflammatory response. DESIGN: Prospective study of human volunteers who were tested on 2 consecutive days, a control day and a treatment day. Each participant served as his or her own control. SETTING: Critical care facility of a university medical center. SUBJECTS: Subjects were eight healthy human volunteers. INTERVENTIONS: Participant subjects were tested on both a baseline day with no intervention and on a treatment day when they received 4 ng/kg intravenous Escherichia coli endotoxin. MEASUREMENTS AND MAIN RESULTS: Continuous electrocardiographic recordings and serial blood sampling (performed every 5 mins) were used to create time-series of heart rate (R-R intervals), neutrophil function (phagocytosis), and plasma cortisol concentrations. For each primary measure, we recorded a significant increase in the regularity (decreased variability) of the functional measurement as assessed by the statistical entity, approximate entropy. CONCLUSIONS: Increased regularity, or decreased variability, of organ functions is a generalized response to systemic inflammation that occurs in widely divergent systems during endotoxemia.

Increase in plasma and surface CD163 levels in patients undergoing coronary artery bypass graft surgery.

Although haptoglobin polymorphism has been shown to be a genetic risk factor in coronary artery disease, its mechanisms of action are incompletely defined. Recently, a macrophage scavenger receptor for the uptake of haptoglobin-hemoglobin (Hp-Hb) complexes was cloned and designated CD163. Macrophage expression of CD163 is increased by glucocorticoids, IL-10 and IL-6. To better understand the in vivo response of CD163 to an inflammatory stimulus and glucocorticoid treatment, we studied 18 patients who underwent elective coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). We report a rapid increase in plasma levels of soluble CD163 by 1 h post-declamping the aorta during CABG surgery with CPB. Furthermore, we demonstrate significant increases in monocyte CD163 on post-operative day 1; 14-fold for patients pre-treated with methylprednisolone and 3-fold for those who did not receive exogenous glucocorticoids. These findings show CD163 to be rapidly mobilized in response to systemic inflammatory stimuli and to be affected significantly by glucocorticoids in vivo. The proposed role of CD163 as a Hp-Hb scavenger and anti-inflammatory molecule, in conjunction with the results of this study, make CD163 an intriguing target for potential manipulation of the acute response to inflammation.

Effect of medium tonicity and dextran on neutrophil function in vitro.

BACKGROUND: Multiple investigations have demonstrated that hypertonic saline (HS) diminishes the response of polymorphonuclear leukocytes (PMNs) to stimulation. Recent meta-analysis suggests that hypertonic saline in dextran (HSD) is clinically superior to HS. No work to date has examined the effect of added dextran on this immunomodulatory property. METHODS: Human PMNs were exposed to media of varying osmolarity (220-360 mOsm/L) and stimulated with f-met-leu-phe with or without dextran present in the medium. Cell volume, respiratory burst, PMN aggregation, and beta(2)-integrin (CD18) expression were measured. RESULTS: Stimulation with f-met-leu-phe increased cell volume, respiratory burst, aggregation, and CD18 expression. The increases in cell volume, respiratory burst, and aggregation were significantly attenuated by exposure to hypertonic medium. The addition of dextran to the media did not change the results. CONCLUSION: The alterations in PMN function associated with HS are not changed or attenuated by the addition of dextran, suggesting that the clinically superior HSD may have effects similar to HS in mitigating the tissue damage associated with activated PMNs.