Publications by authors named "James Mirocha"

184 Publications

Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19: A Randomized, Controlled Pilot Trial.

Chest 2021 Feb 20. Epub 2021 Feb 20.

Department of Medicine, Cedars Sinai Medical Center, Los Angeles, CA.

Background: Severity of illness in COVID-19 is consistently lower in women. A focus on sex as a biological factor may suggest a potential therapeutic intervention for this disease. We assessed whether adding progesterone to standard of care (SOC) would improve clinical outcomes of hospitalized men with moderate to severe COVID-19.

Research Question: Does short-term subcutaneous administration of progesterone safely improve clinical outcome in hypoxemic men hospitalized with COVID-19?

Study Design And Methods: We conducted a pilot, randomized, open-label, controlled trial of subcutaneous progesterone in men hospitalized with confirmed moderate to severe COVID-19. Patients were randomly assigned to receive SOC plus progesterone (100 mg subcutaneously twice daily for up to 5 days) or SOC alone. In addition to assessment of safety, the primary outcome was change in clinical status on day 7. Length of hospital stay and number of days on supplemental oxygen were key secondary outcomes.

Results: Forty-two patients were enrolled from April 2020 to August 2020; 22 were randomized to the control group and 20 to the progesterone group. Two patients from the progesterone group withdrew from the study before receiving progesterone. There was a 1.5-point overall improvement in median clinical status score on a seven-point ordinal scale from baseline to day 7 in patients in the progesterone group as compared with control subjects (95% CI, 0.0-2.0; P = .024). There were no serious adverse events attributable to progesterone. Patients treated with progesterone required three fewer days of supplemental oxygen (median, 4.5 vs 7.5 days) and were hospitalized for 2.5 fewer days (median, 7.0 vs 9.5 days) as compared with control subjects.

Interpretation: Progesterone at a dose of 100 mg, twice daily by subcutaneous injection in addition to SOC, may represent a safe and effective approach for treatment in hypoxemic men with moderate to severe COVID-19.

Trial Registry: ClinicalTrials.gov; No.: NCT04365127; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.02.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896492PMC
February 2021

Quality of Life Outcomes After Modified Selective Neurectomy for Postfacial Paralysis Synkinesis.

Facial Plast Surg Aesthet Med 2021 Feb 19. Epub 2021 Feb 19.

Center for Advanced Facial Plastic Surgery, Beverly Hills, California, USA.

Until now, quality of life (QOL) outcomes after modified selective neurectomy for postfacial paralysis synkinesis (PFPS) have not been assessed. To evaluate QOL outcomes among patients with PFPS who underwent modified selective neurectomy. The medical records of patients aged ≥18 years with PFPS who underwent modified selective neurectomy during a 6-year period were reviewed. QOL outcomes were measured using the Facial Clinimetric Evaluation (FaCE) scale and Synkinesis Assessment Questionnaire (SAQ). At <1 year after selective neurectomy, there was improvement in mean SAQ (from 26.6 [95% confidence interval {CI}, 23.7-29.5] to 21.4 [95% CI, 19.5-23.3];  < 0.0001). Mean FaCE scores improved (from 47.1 [95% CI, 43.6-50.6] to 62.6 [95% CI, 58.7-66.5];  < 0.0001), with improvements in all subscores except lacrimal control scores (from 61.7 [95% CI, 52.6-70.9] to 62.2 [95% CI, 53.6-70.9];  = 0.91). At >1 year after surgery, there was improvement in mean SAQ score (from 28.8 [95% CI, 26.0-31.6] to 23.4 [95% CI, 21.0-25.7];  < 0.0001). Mean FaCE scores improved (from 45.9 [95% CI, 41.6-50.3] to 59.4 [95% CI, 53.6-65.2];  < 0.0001), with improvements in all subscores except eye comfort and lacrimal control (from 52.4 [95% CI, -40.8-64.0] to 56.8 [95% CI, 45.5-68.0];  = 0.36), and lacrimal control scores worsened (from 68.0 [95% CI, 56.7-79.2] to 56.3 [95% CI, 44.8-67.7];  = 0.023). Modified selective neurectomy results in QOL improvements in patients with PFPS.
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http://dx.doi.org/10.1089/fpsam.2020.0485DOI Listing
February 2021

Gene expression comparison between primary estrogen receptor-positive and triple-negative breast cancer with paired axillary lymph node metastasis.

Breast J 2021 Jan 19. Epub 2021 Jan 19.

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

The aim of this study is to characterize and compare changes in gene expression patterns of paired axillary lymph node (ALN) metastases from estrogen receptor (ER)-positive and triple-negative (TNBC) primary breast cancer (PBC). Patients with stage 2-3 PBC with macrometastasis to an ALN were selected. Gene expression of 2567 cancer-associated genes was analyzed with the HTG EdgeSeq system coupled with the Illumina Next Generation Sequencing (NGS) platform. Changes in gene expression between ER/PR-positive, HER2-negative PBC, and their paired ALN metastases were compared with TNBC and their paired ALN metastases. Fourteen pairs of ER-positive and paired ALN metastasis were analyzed. Compared with the PBC, ALN metastasis had 673 significant differentially expressed genes, including 348 upregulated genes and 325 downregulated genes. Seventeen pairs of TNBC and paired ALN metastasis were analyzed. ALN metastasis had 257 significant differentially expressed genes, including 123 upregulated genes and 134 downregulated genes. When gene expression of the ALN for ER-positive PBC was compared to that of TNBC, 97 genes were upregulated in both, and 115 genes were similarly downregulated. Common upregulated genes were associated with cell death, necrosis, and homeostasis. Common downregulated genes were those of migration, degradation of extracellular matrix, and invasion. Although ER-positive PBC and TNBC have a distinct gene expression profiles and distinct changes from PBC to ALN metastases, a significant number of genes are similarly up- or downregulated. Understanding the role of these common genomic changes may provide clues to understanding the metastatic process itself.
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http://dx.doi.org/10.1111/tbj.14119DOI Listing
January 2021

Personalized treatments for depressive symptoms in patients with advanced heart failure: A pragmatic randomized controlled trial.

PLoS One 2021 7;16(1):e0244453. Epub 2021 Jan 7.

Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.

Objectives: Heart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months.

Methods: Trial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed.

Conclusions: The current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings.

Registration: ClinicalTrials.Gov Identifier: NCT03688100.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244453PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790529PMC
January 2021

Effect of nasal fluticasone exhalation delivery system on Eustachian tube dysfunction.

Int Forum Allergy Rhinol 2021 Feb 2;11(2):204-206. Epub 2020 Nov 2.

Department of Otolaryngology, University of Louisville, Louisville, KY.

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http://dx.doi.org/10.1002/alr.22728DOI Listing
February 2021

Donor-derived Cell-free DNA Combined With Histology Improves Prediction of Estimated Glomerular Filtration Rate Over Time in Kidney Transplant Recipients Compared With Histology Alone.

Transplant Direct 2020 Aug 15;6(8):e580. Epub 2020 Jul 15.

Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.

Higher Banff inflammation and chronicity scores on kidney transplant biopsies are associated with poorer graft survival, although histology alone has limitations in predicting outcomes. We investigated if integrating donor-derived cell-free DNA (dd-cfDNA, Allosure; CareDx, Inc.) with Banff biopsy scores into a predictive model for estimated glomerular filtration rate over time can improve prognostic assessment versus histology alone.

Methods: We identified 180 kidney transplant patients with dd-cfDNA assessed within 1 mo of biopsy. Using linear mixed-effects models, a prediction model of Banff histology scores and dd-cfDNA on estimated glomerular filtration rate over time was derived. Nested models were compared using the likelihood-ratio test, Akaike Information Criterion, and Bayesian Information Criterion to assess if inclusion of dd-cfDNA into a model consisting of Banff biopsy scores would improve model fit.

Results: Univariate models identified significant covariate-by-time interactions for cg = 3 versus <3 (coefficient: -1.3 mL/min/1.73 m/mo; 95% confidence interval [CI], -2.4 to -0.2; = 0.02) and ci + ct ≥ 3 versus <3 (coefficient: -0.7 mL/min/1.73 m/mo; 95% CI, -1.3 to -0.1; = 0.03) and a trend toward significant covariate-by-time interaction for dd-cfDNA (coefficient: -0.5 mL/min/1.73 m/mo; 95% CI, -1.0 to 0.1; = 0.08). Addition of acute inflammation (i, t, and v), microvascular inflammation (g and ptc), and inflammation in area of interstitial fibrosis and tubular atrophy scores to chronicity scores (cg ≥ 3 and ci + ct ≥ 3) did not improve model fit. However, a model including dd-cfDNA with cg and ci + ct with covariate-by-time interactions had a better model fit compared with cg and ci + ct alone (likelihood-ratio test statistic = 21.1; df = 2; < 0.001).

Conclusions: Addition of dd-cfDNA to Banff biopsy scores provided better prognostic assessment over biopsy characteristics alone.
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http://dx.doi.org/10.1097/TXD.0000000000001027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581058PMC
August 2020

Male Breast Cancer: 13-Year Single Institution Experience.

Am Surg 2020 Oct 25;86(10):1345-1350. Epub 2020 Oct 25.

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Due to the low incidence of male breast cancer (BC), there are few studies evaluating outcomes. We evaluated the clinicopathologic features and outcomes of male BC. Male patients with BC from January 2006 to December 2018 were identified. Of 49 patients, mean age was 64 (range 33-94) years. Of the 27 (55.1%) patients who had genetic testing, 9 (33.3%) had a Breast Cancer gene (BRCA) 1 or 2 mutation. The majority of patients had a mastectomy (n = 43/49, 87.8%) and had invasive ductal carcinoma (n = 47/49, 95.9%). 20 patients (n = 20/43, 46.5%) had positive lymph nodes. 41 (n = 41/47, 87.2%) patients had estrogen receptor positive disease. The majority of patients were pathologic stage 2 (n = 21/46, 45.7%), followed by stage 1 (n = 15/46, 32.6%), stage 3 (n = 6/46, 13.0%), and stage 4 (n = 4/46, 8.7%). Eight patients had the 21-gene recurrence score performed. Of patients with stage 1-3 BC, 10 (n = 10/43, 23.3%) patients had recurrence. With median follow-up of 4.1 (range .6-10.6) years, 5-year overall survival was 82.9% and 5-year disease-free survival was 65.9%. In conclusion, our cohort of patients with male BC had a high incidence of BRCA mutations and most commonly had high-grade estrogen positive stage 2 tumors. Breast conserving surgery was utilized in 4% of patients and genomic testing utilized in 55% of patients.
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http://dx.doi.org/10.1177/0003134820964444DOI Listing
October 2020

Challenges in Ki-67 assessments in pulmonary large-cell neuroendocrine carcinomas.

Histopathology 2021 Apr 29;78(5):699-709. Epub 2020 Nov 29.

Departments of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Aims: To gather the best available evidence regarding Ki-67% values in large-cell neuroendocrine carcinoma (LCNEC) and determine whether certain cut-off values could serve as a prognostic feature in LCNEC.

Methods And Results: Aperio ScanScope AT Turbo, eSlide Manager and ImageScope software (Leica Biosystems) were used to measure Ki-67% in 77 resected LCNEC diagnosed by World Health Organisation (WHO) criteria. Cases were stratified into six classes by 10% Ki-67 increments. Using the Kaplan-Meier method, overall (OS) and disease-free survivals (DFS) were compared by AJCC stage, by six Ki-67% classes and with Ki-67% cut-points ≥20% and ≥40%. Tumours were from 0.9 to 11.5 cm and pathological stages 1-3. The system measured Ki-67% positivity using 4072-44 533 tumour nuclei per case (mean 16610 ± 8039). Ki-67% ranged from 1 to 64% (mean = 26%; median = 26%). Only 16 (21%) tumours had Ki-67% ≥40%. OS ranged from 1 to 298 months (median follow-up = 25 months). DFS ranged from 1 to 276 months (median follow-up = 9 months). OS and DFS differed across AJCC stage (overall log-rank P = 0.038 and P = 0.037). However, neither OS nor DFS significantly correlated with Ki-67% when six or two classes were used with either ≥20% Ki-67 or ≥40% Ki-67 as cut-point. A literature review identified 14 reports meeting our inclusion criteria with ≥10 LCNEC. Reported Ki-67% ranged from 2% to 100%. Problems contributing to variability in Ki-67% measurements are discussed.

Conclusion: Our findings caution against a blanket use of 20%, 40% or other Ki-67% cut-points for LCNEC diagnosis or prognostication.
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http://dx.doi.org/10.1111/his.14277DOI Listing
April 2021

Low Prenatal Vitamin D Metabolite Ratio and Subsequent Postpartum Depression Risk.

J Womens Health (Larchmt) 2021 Jan 6;30(1):113-120. Epub 2020 Oct 6.

Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Depression is a common complication of pregnancy and vitamin D deficiency is one biological risk factor for postpartum depression (PPD). We evaluated the ratio of 24,25(OH)D and 25(OH)D serum concentrations referred to as the Vitamin D Metabolite Ratio (VMR), a new candidate biomarker during pregnancyand its relationship with PPD. Women were enrolled in the first trimester of pregnancy and followed through four timepoints. A total of 89 women had complete depression, biomarker and demographic data and 34% were at risk for PPD (CES-D≥16). Stepwise multiple logistic regression models for PPD risk were carried out with eight predictors. Results showed that only lower VMR, OR = 1.43, 95% CI 1.10-1.86,  = 0.007, and Hispanic/Latina identification, OR = 3.83, 95% CI 1.44-10.92,  = 0.007 were significantly associated with higher PPD risk. Routine prenatal screening for vitamin D metabolites, particularly in Hispanic/Latina women, may identify women at risk for PPD.
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http://dx.doi.org/10.1089/jwh.2019.8209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826430PMC
January 2021

Mentorship Effectiveness in Cardiothoracic Surgical Training.

Ann Thorac Surg 2020 Oct 1. Epub 2020 Oct 1.

Division of Thoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Background: Mentoring is an essential component of cardiothoracic surgery training, yet trainees report varied experiences despite substantial efforts to enhance mentorship opportunities. This study aimed to evaluate mentorship effectiveness and identify gaps in mentorship education.

Methods: A survey was distributed to cardiothoracic surgical trainees in Accreditation Council for Graduate Medical Education-accredited programs (n = 531). Responses to 16 questions concerning trainee experiences, expectations, and perspectives on mentorship were collected. An 11-component mentorship effectiveness tool generated a composite score (0 to 55), with a score of 44 or lower indicating less effective mentorship.

Results: Sixty-seven residents completed the survey (12.6%), with most (83.6%) reporting a current mentor. Trainees with mentors cited "easy to work with and approachable" (44 of 58; 75.9%) as the major criterion for mentor selection, whereas trainees without a mentor reported an inability to identify one who truly reflected the resident's needs (6 of 11; 45.5%). Resident age, gender, race or ethnicity, marital status, family status, postgraduate year, and training program type or size were not associated with having a mentor (P = .15 to .73). The median mentorship effectiveness score was 51 (interquartile range, 44, 55). More than one-third of residents (25 of 67) had either no mentor (n = 6) or less effective mentorship (n = 16), or both (n = 3). Resident and program characteristics were not associated with mentorship effectiveness (P = .39 to .99). Finally, 61.2% of residents had not received education on effective mentorship, and 53.8% did not currently serve as a mentor.

Conclusions: Many resident respondents have either no mentor or less effective mentorship, and most reported not having received education on mentorship. Addressing these gaps in mentorship training and delivery should be prioritized.
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http://dx.doi.org/10.1016/j.athoracsur.2020.07.045DOI Listing
October 2020

Patient satisfaction survey experience among American otolaryngologists.

Am J Otolaryngol 2020 Nov - Dec;41(6):102656. Epub 2020 Aug 5.

Division of Otolaryngology, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America. Electronic address:

Background: Patient Satisfaction (PS) is a commonly used metric in health care settings to assess the quality of care given by physicians. Monitoring physicians in this way may impact physician quality of life. Studies evaluating this impact are not available. This study sought to examine the physician experience of measuring PS among practicing otolaryngologists.

Methods: Using an online survey platform, a 34-item survey was given to practicing otolaryngologists through email distribution. The survey included questions about physician, practice and patient demographics, as well as inquiries regarding the way in which PS was measured and how it affected physician work and personal life. Data from these questions were reviewed and analyzed.

Results: 174 otolaryngologists responded to the survey. A majority of physicians' (55.3%) PS scores had been tracked with 89.9% reporting being tracked for a length of at least 1 year. PS scores for individual physicians were noted to be inconsistent and vary significantly between reports. Measuring patient satisfaction led to increased occupational stress, yet most physicians (63.8%) felt the monitoring did not lead to improvements in their practice. Some physicians (36.2%) reported that the collection of patient satisfaction scores had negatively influenced the way they practiced medicine, including the pressure to order superfluous tests or to prescribe unnecessary medications.

Conclusion: Overall, physicians are negatively affected by the tracking of patient satisfaction scores. Occupational stress caused by the collection of patient satisfaction scores may contribute to physician burnout.
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http://dx.doi.org/10.1016/j.amjoto.2020.102656DOI Listing
December 2020

Depression in Heart Failure: A Systematic Review.

Innov Clin Neurosci 2020 Apr;17(4-6):27-38

Drs. IsHak, Edwards, Herrera, Lin, Spiegel, Hedrick, Chernoff, Diniz, Danovitch; Mr. Mirocha and Mr. Peterson; and Ms. Hren, Ms. Nigor, Ms. Liu, and Ms. Manoukian and are with the Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center in Los Angeles, California.

: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Studies published from 1988 to 2018 covering depression and HF were identified through the review of the PubMed and PsycINFO databases using the keywords: "depres*" AND "heart failure." Two authors independently conducted a focused analysis, identifying 27 studies that met the specific selection criteria and passed the study quality checks. Patient-reported questionnaires were more commonly adopted than clinician-rated questionnaires, including the Beck Depression Inventory, the Patient Health Questionnaire (PHQ-9), and the Hospital Anxiety and Depression Scale. Six common interventions were observed: antidepressant medications, collaborative care, psychotherapy, exercise, education, and other nonpharmacological interventions. Except for paroxetine, selective serotonin reuptake inhibitors failed to show a significant difference from placebo. However, the collaborative care model including the use of antidepressants showed a significant decrease in PHQ-9 score after one year. All of the psychotherapy studies included a variation of cognitive behavioral therapy and patients showed significant improvements. The evidence was mixed for exercise, education, and other nonpharmacological interventions. This study suggests which types of interventions are more effective in addressing depression in heart failure patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413333PMC
April 2020

Metabolic factors and post-traumatic arthritis may influence the increased rate of surgical site infection in patients with human immunodeficiency virus following total hip arthroplasty.

J Orthop Surg Res 2020 Aug 12;15(1):316. Epub 2020 Aug 12.

Department of Anesthesiology, Kaiser Permanente Los Angeles Medical Center, 4867 Sunset Blvd, 3rd Floor, Suite 3017, Los Angeles, CA, 90027, USA.

Background: The impact of CD4+ T-cell count and highly active antiretroviral therapy (HAART) on the rate of surgical site infection (SSI) in patients with human immunodeficiency virus (HIV) undergoing total hip arthroplasty is still unclear. The goals of this study were to assess the rate of perioperative infection at a large tertiary care referral center and to identify risk factors in HIV+ patients undergoing total hip arthroplasty (THA).

Methods: This study was a prospective, observational study at a single medical center from 2000-2017. Patients who were HIV+ and underwent THA were followed from the preoperative assessment period, through surgery and for a 2-year follow-up period.

Results: Sixteen of 144 HIV+ patients (11%) undergoing THA developed perioperative surgical site infections. Fourteen patients (10%) required revision THA within a range of 12 to 97 days after the initial surgery. The patients' mean age was 49.6 ± 4.5 years, and the most common diagnosis prompting THA was osteonecrosis (96%). Patients who developed SSI had a lower waist-hip ratio (0.86 vs. 0.93, p = 0.047), lower high density lipoprotein cholesterol (45.8 vs. 52.5, p = 0.015) and were more likely to have post-traumatic arthritis (12.5% vs. 0%, p = 0.008). Logistic regression analysis demonstrated that current alcohol use and higher waist-hip ratio were significant protectors against infection (p < 0.05). No other demographic, medical, immunologic parameters, or specific HAART regimens were associated with perioperative infection.

Conclusions: Immunologic status as measured by CD4+ cell count, HIV viral load, and medical therapy do not appear to influence the development of SSI in HIV+ patients undergoing THA. Metabolic factors and post-traumatic arthritis may influence the increased rate of infection in HIV+ patients following THA.
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http://dx.doi.org/10.1186/s13018-020-01827-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425402PMC
August 2020

Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial.

J Clin Endocrinol Metab 2020 09;105(9)

Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.

Context: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied.

Objective: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly.

Design And Setting: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center.

Patients: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment.

Intervention: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day).

Main Outcome Measure: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy.

Results: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ± 1375 per month), arm C was most expensive (mean, $22543 ± 11158 per month), and arm A had an intermediate cost (mean, $14261 ± 1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%.

Conclusions: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.
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http://dx.doi.org/10.1210/clinem/dgaa444DOI Listing
September 2020

Voice-Related Quality of Life in Patients with Chronic Rhinosinusitis.

Ann Otol Rhinol Laryngol 2020 Oct 26;129(10):983-987. Epub 2020 May 26.

Cedars-Sinai Division of Otolaryngology-Head & Neck Surgery, Los Angeles, CA, USA.

Objective: Chronic rhinosinusitis (CRS) has long been associated with vocal dysfunction. However, studies quantifying the presence of voice dysfunction in CRS patients or the effects of functional endoscopic sinus surgery (FESS) are sparse. The goal of this study was to determine the voice-related quality of life in patients undergoing FESS for CRS using the validated Voice Related Quality of Life Survey (VRQL). We correlated the preoperative VRQL scores to the Sino-Nasal Outcome Test (SNOT-22) scores, and we determined the effect of FESS on postoperative VRQL scores.

Methods: Consecutive patients undergoing FESS were preoperatively administered both the VRQL and the SNOT-22 surveys. Spearman (ρ) and Pearson () correlation coefficients were calculated. The VRQL was mailed to patients postoperatively between 3 and 6 months. The paired t-test was used to compare pre- and post-FESS scores.

Results: A total of 102 patients were enrolled, and 81 patients completed the two surveys. A total of 51 (62.9%) patients had raw VRQL score ≥ 10, signifying presence of significant vocal symptoms. The mean ± standard deviation (SD) raw VRQL score of the entire study population was 12.4 ± 4.6, and the mean SNOT-22 score was 37.8 ± 19.2. The Spearman correlation coefficient between VRQL and the total SNOT-22 score was 0.34 ( =.002), and the Pearson correlation coefficient was 0.36 ( = .001). Both correlations were similar, demonstrating that increasing severity of CRS symptoms correlates with decreasing voice-related quality of life (QOL). Seventy patients completed the postoperative survey for an 86% retention rate. Thirty-six of these patients had abnormal preoperative VRQL scores, and these patients improved significantly after FESS. The mean preoperative versus postoperative raw scores were 15.2 ± 5.6 versus 12.5 ± 4.1, respectively ( = .003).

Conclusion: This study demonstrates the increasing presence of vocal complaints with increasing severity of CRS. It also demonstrates that VRQL scores improve after FESS in those patients with preoperative vocal complaints.

Level Of Evidence: IV.
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http://dx.doi.org/10.1177/0003489420924061DOI Listing
October 2020

Immunoglobulin G/albumin staining in tubular protein reabsorption droplets in minimal change disease and focal segmental glomerulosclerosis.

Nephrol Dial Transplant 2020 Mar 19. Epub 2020 Mar 19.

Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background: Some renal biopsies cannot distinguish minimal change disease (MCD) from primary focal segmental glomerulosclerosis (FSGS) because of inadequate sampling and/or a lack of sampled glomeruli with segmental sclerosis. As protein excretion in MCD has been described as being albumin-selective, we examined whether the ratio of immunoglobulin G (IgG)/albumin staining in protein reabsorption droplets (tPRD) might help distinguish MCD from FSGS.

Methods: Frozen tissue from 144 native renal biopsies from patients with nephrotic syndrome and a diagnosis of MCD or FSGS [73 MCD, 30 FSGS tip variant (FSGS-tip), 38 FSGS-not otherwise specified (FSGS-NOS), 3 FSGS collapsing] was retrospectively stained by direct immunofluorescence for IgG and albumin; none of these samples showed diagnostic lesions of FSGS. IgG and albumin staining of tPRD were graded on a scale of 0 to 3+ based on the distribution and intensity of staining.

Results: Mean (standard deviation) IgG/albumin staining ratios were 0.186 ± 0.239 for MCD, 0.423 ± 0.334 for FSGS-tip (P = 0.0001 versus MCD) and 0.693 ± 0.297 for FSGS-NOS (P < 0.0001 versus MCD; P = 0.0001 versus FSGS-tip). Of 84 biopsies with a ratio ≤0.33, 63 (75%) showed MCD, whereas among 21 with a ratio of 1.0, all but one showed FSGS (15 FSGS-NOS).

Conclusions: In summary, IgG/albumin staining in tPRD was correlated with histologic diagnosis in renal biopsies with MCD and FSGS. A ratio of ≤0.33 was associated with MCD, whereas a ratio of 1.0 was most often seen with FSGS-NOS.
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http://dx.doi.org/10.1093/ndt/gfaa039DOI Listing
March 2020

Comparing the rates of methane production in patients with and without appendectomy: results from a large-scale cohort.

Sci Rep 2020 01 21;10(1):867. Epub 2020 Jan 21.

Medically Associated Science and Technology (MAST) program, Department of Medicine, Cedars-Sinai, Los Angeles, 90048, USA.

There is no clear study identifying the microbiome of the appendix. However, in other diverticular conditions, such as diverticulosis, methanogens appear important. We investigated whether patients who had undergone appendectomies had decreased levels of exhaled methane (CH). Consecutive patients who underwent breath testing (BT) from November 2005 to October 2013 were deterministically linked to electronic health records. The numbers of patients with CH ≥ 1 ppm (detectable) and ≥ 3 and ≥ 10 ppm (excess) were compared between patients who did and did not undergo appendectomy using a multivariable model adjusted for age and sex. Of the 4977 included patients (48.0 ± 18.4 years, 30.1% male), 1303 (26.2%) had CH ≥ 10 ppm, and 193 (3.9%) had undergone appendectomy. Appendectomy was associated with decreased odds of CH ≥ 1, ≥ 3, and ≥ 10 ppm (ORs (95% CI) = 0.67 (0.47-0.93), p = 0.02; 0.65 (0.46-0.92), p = 0.01; and 0.66 (0.46-0.93), p = 0.02, respectively). Additionally, the percentage of CH producers increased 4-fold from the first to ninth decade of life. This is the first study to report that appendectomy is associated with decreased exhaled CH. The appendix may play an active physiologic role as a reservoir of methanogens.
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http://dx.doi.org/10.1038/s41598-020-57662-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972888PMC
January 2020

Impact of the Paris system for reporting urine cytopathology on predictive values of the equivocal diagnostic categories and interobserver agreement.

Cytojournal 2019 22;16:21. Epub 2019 Oct 22.

Address: Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background: The Paris System (TPS) acknowledges the need for more standardized terminology for reporting urine cytopathology results and minimizing the use of equivocal terms. We apply TPS diagnostic terminologies to assess interobserver agreement, compare TPS with the traditional method (TM) of reporting urine cytopathology, and evaluate the rate and positive predictive value (PPV) of each TPS diagnostic category. A survey is conducted at the end of the study.

Materials And Methods: One hundred urine samples were reviewed independently by six cytopathologists. The diagnosis was rendered according to TPS categories: negative for high-grade urothelial carcinoma (NHGUC), atypical urothelial cells (AUC), low-grade urothelial neoplasm (LGUN), suspicious for high-grade urothelial carcinoma (SHGUC), and high-grade urothelial carcinoma (HGUC). The agreement was assessed using kappa. Disagreements were classified as high and low impacts. Statistical analysis was performed.

Results: Perfect consensus agreement was 31%, with an overall kappa of 0.362. Kappa by diagnostic category was 0.483, 0.178, 0.258, and 0.520 for NHGUC, AUC, SHGUC, and HGUC, respectively. Both TM and TPS showed 100% specificity and PPV. TPS showed 43% sensitivity (38% by TM) and 70% accuracy (66% by TM). Disagreements with high clinical impact were 27%. Of the 100 cases, 52 were concurrent biopsy-proven HGUC. The detection rate of biopsy-proven HGUC was 43% by TPS (57% by TM). The rate of NHGUC was 54% by TPS versus 26% by TM. AUC rate was 23% by TPS (44% by TM). The PPV of the AUC category by TPS was 61% versus 43% by TM. The survey showed 33% overall satisfaction.

Conclusions: TPS shows adequate precision for NHGUC and HGUC, with low interobserver agreement for other categories. TPS significantly increased the clinical significance of AUC category. Refinement and widespread application of TPS diagnostic criteria may further improve interobserver agreement and the detection rate of HGUC.
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http://dx.doi.org/10.4103/cytojournal.cytojournal_30_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826565PMC
October 2019

Superiority of Out-of-Office Blood Pressure for Predicting Hypertensive Heart Disease in Non-Hispanic Black Adults.

Hypertension 2019 11 16;74(5):1192-1199. Epub 2019 Sep 16.

From the Smidt Heart Institute, Hypertension Center of Excellence (F.R., R.G.V.), Cedars-Sinai Medical Center, Los Angeles, CA.

Black Americans suffer disproportionately from hypertension and hypertensive heart disease. Out-of-office blood pressure (BP) is more predictive for cardiovascular complications than clinic BP; however, the relative abilities of clinic and out-of-office BP to predict left ventricular hypertrophy in black and white adults have not been established. Thus, we aimed to compare associations of out-of-office and clinic BP measurement with left ventricular hypertrophy by cardiac magnetic resonance imaging among non-Hispanic black and white adults. In this cross-sectional study, 1262 black and 927 white participants of the Dallas Heart Study ages 30 to 64 years underwent assessment of standardized clinic and out-of-office (research staff-obtained) BP and left ventricular mass index. In multivariable-adjusted analyses of treated and untreated participants, out-of-office BP was a stronger determinant of left ventricular hypertrophy than clinic BP (odds ratio per 10 mm Hg, 1.48; 95% CI, 1.34-1.64 for out-of-office systolic BP and 1.15 [1.04-1.28] for clinic systolic BP; 1.71 [1.43-2.05] for out-of-office diastolic BP, and 1.03 [0.86-1.24] for clinic diastolic BP). Non-Hispanic black race/ethnicity, treatment status, and lower left ventricular ejection fraction were also independent determinants of hypertrophy. Among treated Blacks, the differential association between out-of-office and clinic BP with hypertrophy was more pronounced than in treated white or untreated participants. In conclusion, protocol-driven supervised out-of-office BP monitoring provides important information that cannot be gleaned from clinic BP assessment alone. Our results underscore the importance of hypertension management programs outside the medical office to prevent hypertensive heart disease, especially in high-risk black adults. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00344903.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785391PMC
November 2019

Sex differences in crude mortality rates and predictive value of intensive care unit-based scores when applied to the cardiac intensive care unit.

Eur Heart J Acute Cardiovasc Care 2020 Dec 27;9(8):966-974. Epub 2019 Aug 27.

Division of Cardiology, Jewish General Hospital, McGill University, Montreal, QC, Canada.

Background: Limited data exists regarding sex differences in outcome and predictive accuracy of intensive care unit-based scoring systems when applied to cardiac intensive care unit patients.

Methods: We reviewed medical records of patients admitted to cardiac intensive care unit from 1 January 2011-31 December 2016. Sex differences in mortality rates and the performance of intensive care unit-based scoring systems in predicting in-hospital mortality were analyzed. Calibration was assessed by the Hosmer-Lemeshow test and locally weighted scatterplot smoothing curves. Discrimination was assessed using the c statistic and receiver-operating characteristic curve.

Results: Among 6963 patients, 2713 (39%) were women. Overall in-hospital and cardiac intensive care unit mortality rates were similar in women and men (9.1% vs 9.4%, =0.67 and 5.9% vs 6%, =0.88, respectively) and in age and major diagnosis subgroups. Of the scoring systems, Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment had poor calibration (Hosmer-Lemeshow value <0.001), while Simplified Acute Physiology Score II performed better (Hosmer-Lemeshow value 0.09), in both women and men. All scores had good discrimination (C statistics >0.8). In the subgroups of acute myocardial infarction and heart failure patients, all scores had good calibration (Hosmer-Lemeshow >0.001) and discrimination (C statistic >0.8) while in diagnosis subgroups with highest mortality, the calibration varied among scores and by sex, and discrimination was poor.

Conclusions: No sex differences in mortality were seen in cardiac intensive care unit patients. The mortality predictive value of intensive care unit-based scores is limited in both sexes and variable among different subgroups of diagnoses.
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http://dx.doi.org/10.1177/2048872619872129DOI Listing
December 2020

Prognostic factors influencing survival in small bowel neuroendocrine tumor with liver metastases.

J Surg Oncol 2019 Nov 8;120(6):926-931. Epub 2019 Aug 8.

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Resection of liver metastasis in small bowel neuroendocrine tumors (SBNET) may improve survival, however, factors influencing prognosis are unclear. We evaluated how the extent of resection influences outcomes.

Methods: Patients with SBNET with liver metastasis from 1990 to 2013 who underwent resection of the primary tumor were identified. Outcomes among patients undergoing complete resection (CR), partial resection (PR), or no resection (NR) of liver metastases with resection of the primary tumor only were compared.

Results: One hundred eleven patients met the criteria. The median number of liver lesions was seven and median lesions resected was one. Fifty (45%) patients had NR, 41 (36.9%) underwent CR, and 20 (18.1%) underwent PR. The 5-year overall survival (OS) was 79.4% for NR, 84.7% for PR, and 100% for CR, demonstrating a trend that CR was best, followed by PR then NR (P = .02). 10-year OS showed no significant differences (72.7% NR; 84.7% PR; 82.5% CR; P = .10). Greater than 10 liver lesions (hazard ratio [HR] 3.6; P = 0.04) or receiving chemotherapy (HR 3.7; P = .03) were negative predictors of survival.

Conclusion: The extent of resection of liver disease in SBNET influenced survival at 5 years but not at 10 years. In addition, more than 10 liver lesions and chemotherapy were predictors of mortality.
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http://dx.doi.org/10.1002/jso.25657DOI Listing
November 2019

Impact of Resident and Fellow Participation on Surgical Outcomes in Breast Conserving Surgery for Invasive Breast Cancer.

J Surg Educ 2020 Jan - Feb;77(1):144-149. Epub 2019 Aug 1.

Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address:

Objective: Few studies examine the impact of surgical trainee involvement on tumor-free margins in breast conserving surgery (BCS). Our objective was to investigate the impact of resident and fellow involvement on positive margins rates following BCS for invasive breast cancer (BC).

Design: We identified female patients who had BCS for BC between January 2005 to December 2015.

Setting: Tertiary care hospital.

Participants: Around 1089 patients were identified from a prospectively maintained database.

Results: Of 1089 patients, mean age was 63 (range 43-99) years. Around 768 patients (70.1%) required preoperative localization, and 328 patients (29.9%) had a palpable cancer. Nonpalpable cancers had a smaller volume of specimen tissue excised (p = 0.0005) compared to palpable cancers, and no significant difference was observed in the positive margin rate between the nonpalpable group compared to the palpable group (24.7% nonpalpable vs. 25.3% palpable, p = 0.88). Nonpalpable cancer positive margin rates were 23.9% (n = 102/427) for cases performed by an attending surgeon, 25.0% (n = 15/60) with a junior resident (PGY 2-3), 28.6% (n = 8/28) with a senior resident (PGY 4-5), and 25.7% (n = 65/253) with a fellow, which were not statistically significant (p = 0.89). Palpable cancer positive margin rates were 27.6% (n = 47/170) for cases performed by an attending, 13.9% (n = 5/36) with an intern (PGY-1), 40.9% (n = 9/22) with a junior resident, 0% (n = 0/8) with a senior resident, and 23.9% (n = 22/92) with a fellow, which were also not significantly different (p = 0.07).

Conclusion: Resident and fellow participation in BCS for BC does not appear to impact the rate of positive margins.
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http://dx.doi.org/10.1016/j.jsurg.2019.07.014DOI Listing
August 2019

Effect of Percutaneous Suction Thromboembolectomy on Improved Right Ventricular Function.

Tex Heart Inst J 2019 Apr 1;46(2):115-119. Epub 2019 Apr 1.

Venous thromboembolism is a leading cause of cardiovascular death. Historically, surgical intervention has been associated with high morbidity rates. Pharmacologic therapy alone can be inadequate for patients with substantial hemodynamic compromise, so minimally invasive procedures are being developed to reduce clot burden. We describe our initial experience with using the AngioVac system to remove thromboemboli percutaneously. We reviewed all suction thromboembolectomy procedures performed at our institution from March 2013 through August 2015. The main indications for the procedure were failed catheter-directed therapy, contraindication to thrombolysis, bleeding-related complications, and clot-in-transit phenomena. We collected details on patient characteristics, procedural indications, thrombus location, hemodynamic values, cardiac function, pharmacologic support, and survival to discharge from the hospital. The Wilcoxon signed-rank test was used for statistical analysis. Thirteen patients (mean age, 56 ± 15 yr; 10 men) underwent suction thromboembolectomy; 10 (77%) survived to hospital discharge. The median follow-up time was 74 days (interquartile range [IQR], 23-221 d). Preprocedurally, 8 patients (62%) had severe right ventricular dysfunction; afterwards, 11 (85%) had normal function or mild-to-moderate dysfunction, and only 2 (17%) had severe dysfunction (=0.031). Percutaneous suction thromboembolectomy, a promising therapeutic option for patients, appears to be safe, and we found it to be associated with improved right ventricular function.
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http://dx.doi.org/10.14503/THIJ-17-6551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555294PMC
April 2019

Allocation of the Highest Quality Kidneys and Transplant Outcomes Under the New Kidney Allocation System.

Am J Kidney Dis 2019 05 28;73(5):605-614. Epub 2019 Mar 28.

Division of Nephrology, Department of Medicine, Comprehensive Transplant Center, Cedars Sinai Medical Center, West Hollywood. Electronic address:

Rationale & Objective: Increased access to transplantation for highly sensitized candidates following implementation of the kidney allocation system (KAS) has been mostly due to higher use of organs with a lower kidney donor profile index (KDPI; a quality metric for donated kidneys), although changes in allocation of these organs was not intended. It is unclear whether clinical outcomes have changed in association with these changes. We investigated the use of kidneys with low and high KDPI scores over time and whether KDPI score affects patient and graft survival differently across varying levels of allosensitization.

Study Design: Observational cohort study.

Setting & Participants: Adult (aged ≥18 years) recipients of a deceased donor kidney transplant between October 1, 2009, and September 30, 2017 (Organ Procurement and Transplantation Network/United Network for Organ Sharing database; n = 84,451).

Predictors: Calculated panel-reactive antibody (cPRA) level (0%, 1%-79%, 80%-89%, 90%-98%, and 99%-100%) and KDPI score (≤20%, 21%-85%, and >85%).

Outcomes: Death, graft loss.

Analytical Approach: Time to event.

Results: Allocation of kidneys with KDPI scores ≤ 20% and KDPI scores of 21% to 85% to recipients with cPRA levels ≥ 99% increased 4-fold following implementation of the KAS with little change in allocation of kidneys with KDPI scores > 85%. Patient survival and graft loss were strongly associated with KDPI score, whereas the association with cPRA level was minimal. There was no evidence of a differential effect of KDPI scores across the range of cPRA levels on patient survival (P for interaction=0.06-0.9) or graft loss (P for interaction=0.5-0.9). Patient survival at 5 years among the 5 cPRA groups ranged from 87.2% to 89.8% for recipients of kidneys with KDPI scores ≤ 20% (P=0.2), 82.8% to 85.5% for KDPI scores of 21% to 85% (P=0.04), and 70.2% to 79.2% for KDPI scores > 85% (P=0.2). Cumulative incidence of graft loss by cPRA level ranged from 7.7% to 10.6% for recipients of kidneys with KDPI scores ≤ 20% (P=0.2), 11.8% to 15.0% for KDPI scores of 21% to 85% (P < 0.001), and 19.8% to 29.7% for KDPI scores > 85% (P = 0.4).

Limitations: Lack of data for crossmatches, donor-specific antibodies, and immunomodulation.

Conclusions: Highly sensitized recipients received kidneys with lower KDPI scores following implementation of the KAS, reducing access to these kidneys by less-sensitized candidates. KDPI score has a stronger association with patient survival and graft loss than cPRA level. The association of KDPI score with these outcomes was not modified by the recipient's level of sensitization. The impact of the redistribution of kidneys with low KDPI scores on outcomes among less-sensitized recipients needs further evaluation.
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http://dx.doi.org/10.1053/j.ajkd.2018.12.036DOI Listing
May 2019

Menopausal Status and Outcomes of BRCA Mutation Carriers with Breast Cancer.

Am Surg 2018 Oct;84(10):1584-1588

Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.

Outcomes based on menopausal status of breast cancer (BC) patients who are BRCA mutations carriers (BRCAm) are not well known. A prospective database identified 88 BRCAm with BC from 2005 to 2015. Of the 88 patients, 68 (77.3%) women were premenopausal (Pre-M) and 20 (22.7%) were postmenopausal (Post-M). In the Pre-M group, 52.9 per cent of patients had triple-negative (TN) BC, whereas in the Post-M group, there were more estrogen receptor +(65%; = 0.129) and less TN (25%; = 0.041) tumors. Median tumor size was significantly larger in the Pre-M group compared with the Post-M group ( <0.001). Pre-M women were more likely to present with stage III cancers (14.7% 0%, respectively, = 0.082). Ten-year overall survival was 87.9 per cent in the Pre-M group and 93.8 per cent in the Post-M group ( = 0.44), and 25.3 per cent of Pre-M women had recurrences compared with 11.5 per cent of Post-M women ( = 0.24). Premenopausal BRCAm with BC are more likely to have TN, higher stage disease, and twice the number of recurrences at 10 years than Post-M BRCAm. Our study is the first to show worse BC outcomes for Pre-M BRCAm compared with Post-M BRCAm women.
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October 2018

Combined Heart and Kidney Transplantation: Clinical Experience in 100 Consecutive Patients.

J Am Heart Assoc 2019 02;8(4):e010570

1 Division of Cardiology Cedars-Sinai Smidt Heart Institute the Multiorgan Transplant Program Cedars-Sinai Medical Center Los Angeles CA.

Background Combined heart and kidney transplantation ( HKT x) is performed in patients with severe heart failure and advanced renal insufficiency. We analyzed the long-term survival after HKT x, the influence of age and dialysis status, the rates of cardiac rejection, and the influence of sensitization. Methods and Results From June 1992 to December 2016, we performed 100 HKT x procedures. We compared older (≥60 years, n=53) with younger (<60 years, n=47) recipients, and recipients on preoperative dialysis (n=49) and not on dialysis (n=51). We analyzed actuarial freedom from any cardiac rejection, acute cellular rejection, and antibody-mediated rejection, and survival rates by sensitized status with panel-reactive antibody levels <10%, 10% to 50%, and >50%, and compared these survival rates with those from the United Network for Organ Sharing database. There was no difference in 15-year survival between the 2 age groups (35±12.4% and 49±17.3%, ≥60 versus <60 years; P=0.45). There was no difference in 15-year survival between the dialysis and nondialysis groups (44±13.4% and 37±15.2%, P=0.95). Actuarial freedom from any cardiac rejection ( acute cellular rejection >0 or antibody-mediated rejection >0) was 92±2.8% and 84±3.8%, acute cellular rejection (≥2R/3A) 98±1.5% and 94±2.5%, and antibody-mediated rejection (≥1) 96±2.1% and 93±2.6% at 30 days and 1 year after HKT x. There was no difference in the 5-year survival among recipients by sensitization status with panel-reactive antibody levels <10%, 10% to 50%, and >50% (82±5.9%, 83±10.8%, and 92±8.0%; P=0.55). There was no difference in 15-year survival after HKT x between the United Network for Organ Sharing database and our center (38±3.2% and 40±10.1%, respectively; P=0.45). Conclusions HKT x is safe to perform in patients 60 years and older or younger than 60 years and with or without dialysis dependence, with excellent outcomes. The degree of panel-reactive antibody sensitization did not appear to affect survival after HKT x.
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http://dx.doi.org/10.1161/JAHA.118.010570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405671PMC
February 2019

Early clinical experience using donor-derived cell-free DNA to detect rejection in kidney transplant recipients.

Am J Transplant 2019 06 29;19(6):1663-1670. Epub 2019 Mar 29.

Division of Nephrology, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California.

Donor-derived cell-free DNA (dd-cfDNA) became Medicare reimbursable in the United States in October 2017 for the detection of rejection in kidney transplant recipients based on results from its pivotal validation trial, but it has not yet been externally validated. We assessed 63 adult kidney transplant recipients with suspicion of rejection with dd-cfDNA and allograft biopsy. Of these, 27 (43%) patients had donor-specific antibodies and 34 (54%) were found to have rejection by biopsy. The percentage of dd-cfDNA was higher among patients with antibody-mediated rejection (ABMR; median 1.35%; interquartile range [IQR]: 1.10%-1.90%) compared to those with no rejection (median 0.38%, IQR: 0.26%-1.10%; P < .001) and cell-mediated rejection (CMR; median: 0.27%, IQR: 0.19%-1.30%; P = .01). The dd-cfDNA test did not discriminate patients with CMR from those without rejection. The area under the ROC curve (AUC) for CMR was 0.42 (95% CI: 0.17-0.66). For ABMR, the AUC was 0.82 (95% CI: 0.71-0.93) and a dd-cfDNA ≥0.74% yielded a sensitivity of 100%, specificity 71.8%, PPV 68.6%, and NPV 100%. The dd-cfDNA test did not discriminate CMR from no rejection among kidney transplant recipients, although performance characteristics were stronger for the discrimination of ABMR.
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http://dx.doi.org/10.1111/ajt.15289DOI Listing
June 2019

Randomized Clinical Trial Comparing Laparoscopic Versus Ultrasound-Guided Transversus Abdominis Plane Block in Minimally Invasive Colorectal Surgery.

Dis Colon Rectum 2019 02;62(2):203-210

Division of Colon and Rectal Surgery, Cedars-Sinai Medical Center, Los Angeles, California.

Background: Transversus abdominis plane block may improve analgesia after colorectal surgery; however, techniques remain unstandardized and results are conflicting.

Objective: The purpose of this study was to compare laparoscopic and ultrasound-guided transversus abdominis plane block with no block in minimally invasive colorectal surgery.

Design: This was a randomized controlled trial.

Settings: The study was conducted at an urban teaching hospital.

Patients: Patients undergoing laparoscopic colorectal surgery were included.

Interventions: The intervention included 2:2:1 randomization to laparoscopic, ultrasound-guided, or no transversus abdominis plane block.

Main Outcome Measures: Morphine use in the first 24 hours after surgery was measured.

Results: The study cohort included 107 patients randomly assigned to laparoscopic (n = 41), ultrasound-guided (n = 45), or no transversus abdominis plane block (n = 21). Mean age was 50.4 years (SD ± 18 y), and 50 patients (47%) were men. Laparoscopic transversus abdominis plane block was superior to ultrasound-guided (p = 0.007) and no transversus abdominis plane block (p = 0.007), with median (interquartile range) total morphine used in the first 24 hours postoperatively of 17.6 mg (6.6-33.9 mg), 34.0 mg (16.4-44.4 mg), and 31.6 mg (18.4-44.4 mg). At 48 hours, laparoscopic transversus abdominis plane block remained superior to ultrasound-guided (p = 0.03) and no transversus abdominis plane block (p = 0.007) with median (interquartile range) total morphine used at 48 hours postoperatively of 26.8 mg (15.5-45.8 mg), 44.0 mg (27.6-70.0 mg), and 60.8 mg (34.8-78.8 mg). Mean hospital stay was 5.1 ± 3.1 days without any intergroup differences. Overall complications were similar between groups.

Limitations: Treatment teams were not blinded and there was operator dependence of techniques and variable timing of the blocks.

Conclusions: Laparoscopic transversus abdominis plane block is superior to ultrasound-guided and no transversus abdominis plane block in achieving pain control and minimizing opioid use in the first 24 hours after colorectal surgery. A large, multicenter, randomized trial is needed to confirm our findings. See Video Abstract at http://links.lww.com/DCR/A822.
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http://dx.doi.org/10.1097/DCR.0000000000001292DOI Listing
February 2019

Declining Rates of Referral for Irritable Bowel Syndrome Without Constipation at a Tertiary Care Center.

Dig Dis Sci 2019 01 15;64(1):182-188. Epub 2018 Oct 15.

GI Motility Program, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.

Background: Irritable bowel syndrome (IBS) is a common chronic disorder of the gastrointestinal tract. Several treatments have been developed, including rifaximin for the treatment of IBS without constipation (non-IBS-C), but no studies have evaluated the effect of these therapies on patient referral rates to tertiary care gastroenterology clinics.

Aim: To assess referral patterns for IBS patients at a tertiary motility clinic over a 10-year period.

Methods: Data from consecutive patients referred to the clinic during 2006-2016 were analyzed. Trends in the proportion of referrals and prior rifaximin use in IBS-C versus non-IBS-C groups were compared.

Results: A total of 814 adult patients were referred to a single physician panel for IBS-related symptoms. Of these, 776 were included in the study [528 females (68%), average age 45.7 ± 15.9 years), comprising 431 IBS-C (55.5%) and 345 non-IBS-C (44.5%) patients. The proportion of non-IBS-C referrals declined significantly from 53.0% in 2006 to 27.3% in 2016 (Chi-square, p < 0.0001, Cochran-Armitage trend test p = 0.0001), and the proportion of IBS-C referrals increased significantly from 46.9% in 2006 to 72.7% in 2016 (Chi-square, p < 0.0001, Cochran-Armitage trend test p = 0.0004). Non-IBS-C referrals with prior rifaximin use significantly increased from 22.7% in 2006 to 66.7% in 2016 (Cochran-Armitage trend test, p = 0.008).

Conclusions: The results indicate a significantly declining tertiary care referral rate for non-IBS-C over the past decade. While not directly linked, there has been an increase in rifaximin use in the same population during the same time interval.
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http://dx.doi.org/10.1007/s10620-018-5302-2DOI Listing
January 2019

Heterogeneity of Fibrosis in Liver Biopsies of Patients With Heart Failure Undergoing Heart Transplant Evaluation.

Am J Surg Pathol 2018 12;42(12):1617-1624

Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center.

Liver biopsies are commonly performed in heart transplant candidates to confirm congestive hepatopathy (CH) and to assess the degree of fibrosis. Heterogeneity of fibrosis is frequent in CH, making it difficult to stage fibrosis. In this study, we evaluated the prevalence of heterogeneity of fibrosis and nodular regenerative hyperplasia (NRH) in liver biopsies with CH secondary to heart failure. Fifty liver biopsies with CH secondary to heart failure were reviewed. The fibrosis was scored on trichrome stain as follows: stage 0 for no fibrosis, stage 1 for zone 3 fibrosis, stage 2 for zone 3 and portal fibrosis, stage 3 for bridging fibrosis, and stage 4 for cirrhosis. Both stage 3 and stage 4 fibrosis were classified as advanced fibrosis. A predominant pattern of fibrosis and a secondary pattern of fibrosis, defined as a different stage of fibrosis seen in at least 10% of the biopsy material, if present, were recorded. A biopsy was considered to show heterogenous fibrosis if there was at least a 2 stage difference between the predominant and secondary patterns. Thirteen biopsies (26%) showed heterogenous fibrosis. Sixteen biopsies (32%) showed some evidence of advanced fibrosis: 5 had uniform advanced fibrosis, 4 had predominant pattern of advanced fibrosis, and advanced fibrosis was focal in 7 biopsies from 6 patients. NRH-type changes were seen in 9 of 50 biopsies (18%). In conclusion, our study showed heterogenous fibrosis in the liver biopsy of a quarter of patients with CH due to heart failure, highlighting the limitations of fibrosis assessment in the biopsies, and suggests that correlation with the complete clinical information is essential for management decisions.
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http://dx.doi.org/10.1097/PAS.0000000000001163DOI Listing
December 2018