Association of Medicaid expansion with access to thyroidectomy for benign disease at high-volume centers.

BACKGROUND: Insurance-based disparities in access to thyroidectomy are well established. Patients undergoing thyroidectomy by high-volume surgeons have fewer complications and better postoperative outcomes. The aim of this study is to evaluate the association of Medicaid expansion with access to high-volume centers for thyroidectomy for benign disease. METHODS: The Vizient Clinical Data Base was queried for adult operations for benign thyroid disease from 2010 to 2019. Centers were sorted by volume into quartiles. Difference-in-difference analysis evaluated changes in insurance populations in expansion and non-expansion states after Medicaid expansion. Odds of patients undergoing operations in the 4 volume quartiles after stratifying by insurance and Medicaid expansion status were calculated. RESULTS: A total of 82,602 patients underwent operations at 364 centers. Expansion states increased Medicaid coverage in all volume quartiles compared to non-expansion states after Medicaid expansion (Q1, +4.87%, Q2, +5.35%, Q3, +8.57%, Q4, +4.62%, P < .002 for all). After Medicaid expansion, Medicaid patients had higher odds of undergoing operation at lower volume hospitals compared to the highest volume centers in both expansion states (Q1, ref, Q2, 1.82, Q3, 1.76, Q4, 1.67, P < .001) and non-expansion states (Q1, ref, Q2, 1.54, Q3, 2.04, Q4, 1.44, P < .001). Privately insured patients were most likely to undergo their operation at the highest volume centers in all states (E: Q1, ref, Q2, 0.78, Q3, 0.74, Q4, 0.66, P < .001; NE: Q1, ref, Q2, 0.89, Q3, 0.58, Q4, 0.85, P < .001). CONCLUSION: Medicaid expansion increased Medicaid coverage in expansion states, but Medicaid patients in both expansion and non-expansion states were less likely to be operated on at the highest volume centers compared to privately insured patients. Persistent barriers to accessing high-volume care still exists for Medicaid patients.

Socioeconomic status as a predictor of post-operative mortality and outcomes in carotid artery stenting vs. carotid endarterectomy.

Background: The association between low socioeconomic status (SES) and worse surgical outcomes has become an emerging area of interest. Literature has demonstrated that carotid artery stenting (CAS) poses greater risk of postoperative complications, particularly stroke, than carotid endarterectomy (CEA). This study aims to compare the impact of low SES on patients undergoing CAS vs. CEA. Methods: The National Inpatient Sample (NIS) was queried for patients undergoing CAS and CEA from 2010 to 2015. Patients were stratified by highest and lowest median income quartiles by zip code and compared through demographics, hospital characteristics, and comorbidities defined by the Charlson Comorbidity Index (CCI). Primary outcome was in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), post-operative stroke, sepsis, and bleeding requiring reoperation.Multivariable logistic regression was used to determine the effect of SES on outcomes. Results: Five thousand four hundred twenty-five patients underwent CAS (Low SES: 3,516 (64.8%); High SES: 1,909 (35.2%) and 38,399 patients underwent CEA (Low SES: 22,852 (59.5%); High SES: 15,547 (40.5%). Low SES was a significant independent predictor of mortality [OR = 2.07 (1.25-3.53); p = 0.005] for CEA patients, but not for CAS patients [OR = 1.21 (CI 0.51-2.30); p = 0.68]. Stroke was strongly associated with low SES, CEA patients (Low SES = 1.5% vs. High SES = 1.2%; p = 0.03), while bleeding was with high SES, CAS patients (Low SES = 5.3% vs. High SES = 7.1%; p = 0.01). CCI was a strong predictor of mortality for both procedures [CAS: OR1.45 (1.17-1.80); p < 0.001. CEA: OR1.60 (1.45-1.77); p < 0.001]. Advanced age was a predictor of mortality post-CEA [OR = 1.03 (1.01-1.06); p = 0.01]. While not statistically significant, advanced age and increased mortality trended towards a positive association in CAS [OR = 1.05 (1.00-1.10); p = 0.05]. Conclusions: Low SES is a significant independent predictor of post-operative mortality in patients who underwent CEA, but not CAS. CEA is also associated with higher incidence of stroke in low SES patients. Findings demonstrate the impact of SES on outcomes for patients undergoing carotid revascularization procedures. Prospective studies are warranted to further evaluate this disparity.

Effects of the COVID-19 pandemic on endocrine operations in the United States.

BACKGROUND: The COVID-19 pandemic disrupted the United States (US) healthcare system. Endocrine operations are predominantly elective and were likely affected. Therefore, our aim was to determine the effect of the pandemic on endocrine operations. STUDY DESIGN: The Vizient Clinical Data Base® was examined for cases from 1/2019-12/2022 using ICD10 and CPT codes for thyroid, parathyroid, and adrenal operations. Control chart analysis identified trends in operative volume. Negative binomial regression was utilized to analyze demographic trends. RESULTS: Monthly volumes for all operations from 515 hospitals decreased at the beginning of 2020, except for operations for adrenal malignancy. Inpatient operations (Thyroid -17.1%, Parathyroid -20.9%, p â€‹< â€‹0.001 for both) experienced more significant and longer lasting disruptions than outpatient operations (Thyroid -2.6%, p â€‹= â€‹0.883, Parathyroid -9.1%, p â€‹= â€‹0.098). CONCLUSIONS: The COVID-19 pandemic disrupted endocrine operations across the US. While all adrenal operations and outpatient thyroid and parathyroid operations have returned to pre-pandemic levels, inpatient operations for thyroid and parathyroid remain decreased.

Malpractice litigation after thyroid surgery: What factors favor surgeons?

BACKGROUND: Litigation impacts physicians financially, reputationally, and professionally. Although thyroid surgery has favorable patient outcomes, litigation persists. We aimed to characterize malpractice claims after thyroidectomy and investigate which factors favor physicians. METHODS: We queried the Westlaw legal database using the terms "thyroidectomy" and "medical malpractice" to identify malpractice cases brought against surgeons from 1949 to 2022. We collected and analyzed demographic; clinical; surgical; and legal data, including year, cause for initiating litigation, verdict, state where the lawsuit was brought, and the state's tort reform status. RESULTS: Of the 68 cases included, medical negligence was the most common cause of action, followed by failure to provide adequate informed consent. The most common inciting surgical event was recurrent laryngeal nerve injury (n = 34, 50%). Surgeons prevailed more often overall (n = 53, 77.9%) and in 11 (91.7%) of the 12 cases treated at academic institutions. The 3 endocrine surgery fellowship-trained surgeons all prevailed in their cases. Of the 15 cases in which patients prevailed, 12 (80%) of which were decided by a jury, the median damages awarded were $569,668 (interquartile range $341,146-$2,594,050). In the 53 cases won by surgeons, 26 were jury decisions (49.1%). Surgeons prevailed in 87.5% of cases brought in the 24 states with tort reform and in 72.7% in the 44 states without tort reform. CONCLUSION: Non-jury cases and operations done at academic institutions appear to favor decisions for the defendant. Although not statistically significant, all endocrine surgery fellowship-trained defendants won. Where tort reforms are in place, surgeons tend to prevail.

Minimally invasive approach associated with lower resource utilization after aortic and mitral valve surgery.

Objective: To investigate the effect of minimally invasive cardiac surgery (MICS) on resource utilization, cost, and postoperative outcomes in patients undergoing left-heart valve operations. Methods: Data were retrospectively reviewed for patients undergoing single-valve surgery (eg, aortic valve replacement, mitral valve replacement, or mitral valve repair) at a single center from 2018 to 2021, stratified by surgical approach: MICS vs full sternotomy (FS). Baseline characteristics and postoperative outcomes were compared. Primary outcome was high resource utilization, defined as direct procedure cost higher than the third quartile or either postoperative LOS ≥7 days or 30-day readmission. Secondary outcomes were direct cost, length of stay, 30-day readmission, in-hospital and 30-day mortality, and major morbidity. Multiple regression analysis was conducted, controlling for baseline characteristics, operative approach, valve operation, and lead surgeon to assess high resource utilization. Results: MICS was correlated with a significantly lower rate of high resource utilization (MICS, 31.25% [n = 115] vs FS 61.29% [n = 76]; P < .001). Median postoperative length of stay (MICS, 4 days [range, 3-6 days] vs FS, 6 days [range, 4 to 9 days]; P < .001) and direct cost (MICS, $22,900 [$19,500-$28,600] vs FS, $31,900 [$25,900-$50,000]; P < .001) were lower in the MICS group. FS patients were more likely to experience postoperative atrial fibrillation (P = .040) and renal failure (P = .027). Other outcomes did not differ between groups. Controlling for stratified Society of Thoracic Surgeons predicted risk of mortality, cardiac valve operation, and lead surgeon, FS demonstrated increased likelihood of high resource utilization (P < .001). Conclusions: MICS for left-heart valve pathology demonstrated improved postoperative outcomes and resource utilization.

Ambulatory Electrocardiography Monitoring for Early Discharge After Minimally Invasive Valve Surgery.

INTRODUCTION: We sought to compare outcomes after early discharge in patients with and without predischarge diagnosis of arrhythmia following minimally invasive valve surgery (MIVS). MATERIALS AND METHODS: We retrospectively reviewed ambulatory electrocardiography (AECG) datasheets and medical records of patients discharged with 14-d AECG monitoring from our facility between October 2019 and March 2022 ≤ 3 d after MIVS. Baseline and clinical characteristics, arrhythmias during AECG monitoring, and 30-d adverse outcomes were reported for the population and stratified by presence or absence of predischarge arrhythmia. RESULTS: Of 41 patients discharged ≤3 d postoperatively of MIVS, 17 (41.5%) experienced predischarge arrhythmias and 24 (58.5%) did not. The population was predominantly male and White with a median age of 62 y [57, 70]. Baseline and clinical characteristics did not differ between subgroups. Most patients (92.7% [n = 38]) experienced one or more tachyarrhythmias during the AECG monitoring period. There were similar proportions of patients experiencing atrial fibrillation in both groups, but patients with predischarge arrhythmias had higher burden of atrial fibrillation on AECG monitoring (27.60% [6.57%, 100%] versus 1.65% [0.76%, 4.32%]; P = 0.004). The predischarge arrhythmia subgroup had higher proportions of patients experiencing nonsustained ventricular tachycardia but lower proportions experiencing supraventricular tachycardia. There were no mortalities within 30 d of surgery. Six (14.6%) patients were readmitted within 30 d with equal proportions of readmissions between subgroups (P = 0.662). CONCLUSIONS: Early discharge timelines and noninvasive monitoring techniques can allow patients to return to their normal activities quicker in the comfort of their own home with no increased risk of morbidity or mortality.

Does arterial cannulation site for aortic dissection repair impact surgical outcomes?

Background: Establishing cardiopulmonary bypass remains critical to the successful repair of an acute type A aortic dissection. A recent trend away from femoral arterial cannulation has occurred in part due to concerns of stroke risk from retrograde perfusion to the brain. The purpose of this study was to determine if arterial cannulation site for aortic dissection repair impacts surgical outcomes. Methods: A retrospective chart review was performed at Rutgers Robert Wood Johnson Medical School from January 1st, 2011 to March 8th, 2021. Of the 135 patients included, 98 (73%) underwent femoral arterial cannulation, 21 (16%) axillary artery cannulation, and 16 (12%) direct aorta cannulation. The study variables included demographic data, cannulation site, and complications. Results: The mean age was 63.6±14 years, with no difference between the femoral, axillary, and direct cannulation groups. Eighty-four patients (62%) were male, with similar percentages amongst each group. The rates of bleeding, stroke, and mortality specifically due to the arterial cannulation did not significantly differ based on cannulation site. None of the patients had strokes that were attributable to cannulation type. No patients died as a direct complication of arterial access. The overall in-hospital mortality was 22%, similar between groups. Conclusions: This study found no statistically significant different in rates of stroke or other complications based on cannulation site. Femoral arterial cannulation thus remains a safe and efficient choice for arterial cannulation in the repair of acute type A aortic dissection.

Aortic dissection following "ecstasy" use complicated by compartment syndrome.

BACKGROUND: Patients who present to the emergency department (ED) with acute chest pain should receive a thorough history and exam to rule out rare, life-threatening conditions, such as drug-induced acute aortic dissections (AD). CASE PRESENTATION: A 34-year-old man with a history of uncontrolled hypertension, smoking, and "ecstasy" use presented to the ED with an acute type A aortic dissection (AD). Following surgery to repair the dissection, he developed compartment syndrome of the lower extremity requiring muscle excision and neurolysis with subsequent wound debridement procedures. CONCLUSION: Physicians treating adults with symptoms and signs of aortic dissection should take a focused history about substance use and include AD on their differential. In addition, the extremities should be monitored for signs and symptoms of ischemia throughout the acute peri-surgical period(s).

Surgery is Associated With Improved Overall Survival in Patients With Metastatic Gastric Cancer: A National Cancer Database Analysis.

BACKGROUND: The 5-year overall survival (OS) rate for patients with metastatic gastric cancer (mGC) is 5.3%. Surgery for mGC is controversial. METHODS: We identified all mGC patients who received chemotherapy using the National Cancer Database (2004-2015). Patients were grouped according to surgery of: (1) the primary site (PS) only, (2) primary and distant sites (PDS), (3) distant site only (DS), or (4) no surgery (NS). A propensity score adjustment and multivariate regression was used to compare OS. RESULTS: Overall, 18,772 patients met the inclusion criteria: (1) PS (n = 962, 5.1%), (2) PDS (n = 380, 2.1%), (3) DS (n = 984, 5.2%), and 16,446 NS (87.6%). Surgery was associated with improved OS in the PS and PDS groups (hazard ratios: .489 (95% CI: .376-.636); .583 (95% CI: .420-.811), P < .001) (median OS 15.8 and 15.9 months vs 8.6 for NS patients, respectively). CONCLUSIONS: Gastrectomy with or without metastasectomy is associated with improved survival in stage IV gastric cancer patients receiving chemotherapy. This warrants further prospective studies.

Early Discharge After Minimally Invasive Aortic and Mitral Valve Surgery.

BACKGROUND: We investigated patient outcomes in relation to their postoperative length of stay after minimally invasive valve surgery. METHODS: All adults who survived elective, uncomplicated minimally invasive aortic or mitral valve surgery at a single center between 2012 and 2019 were classified by postoperative length of stay: early discharge (≤3 days) or late discharge (>3 days). The trend in early discharge was investigated over the study period, predictors of early discharge were identified using multivariate logistic regression modeling, and 1:1 propensity score matching was used to determine which patients in the late-discharge cohort had similar health to patients discharged early. Adjusted outcomes of 30-day mortality, readmission, and direct costs were analyzed. RESULTS: Among 1262 consecutive patients undergoing minimally invasive valve surgery, 618 were elective and uncomplicated, 25% (n = 162) of whom were discharged early. The proportion of early-discharge patients increased over time (P for trend < .05). A history of congestive heart failure, stroke, or smoking and higher Society of Thoracic Surgeons predictive risk of mortality score negatively predicted early discharge (P < .05). Propensity score matching identified 101 (22%) late-discharge patients comparable with early-discharge patients. Adjusted 30-day mortality and readmission rates were comparable between cohorts. The median direct costs per patient ($20,046 vs $22,124, P < .05) were significantly lower in the early-discharge cohort. CONCLUSIONS: In well-selected patients early discharge after minimally invasive valve surgery was associated with lower costs but comparable postoperative outcomes. About one-fifth of patients who remain in the hospital beyond postoperative day 3 may be candidates for earlier discharge.

Gut Microbiome-Derived Uremic Toxin Levels in Hemodialysis Patients on Different Phosphate Binder Therapies.

INTRODUCTION: Constipation is prevalent in patients with kidney failure partly due to the use of medication, such as phosphate binders. We hypothesized that serum levels of gut microbiome-derived uremic toxins (UTOX) may be affected by the choice of phosphate binder putatively through its impact on colonic transit time. We investigated two commonly prescribed phosphate binders, sevelamer carbonate (SEV) and sucroferric oxyhydroxide (SFO), and their association with gut microbiome-derived UTOX levels in hemodialysis (HD) patients. METHODS: Weekly blood samples were collected from 16 anuric HD participants during the 5-week observational period. All participants were on active phosphate binder monotherapy with either SFO or SEV for at least 4 weeks prior to enrollment. Eight UTOX (7 gut microbiome-derived) and tryptophan were quantified using liquid chromatography-mass spectrometry. Serum phosphorus, nutritional, and liver function markers were also measured. For each substance, weekly individual levels, the median concentration per participant, and differences between SFO and SEV groups were reported. Patient-reported bowel movements, by the Bristol Stool Scale (BSS), and pill usage were assessed weekly. RESULTS: The SEV group reported a 3.3-fold higher frequency of BSS stool types 1 and 2 (more likely constipated, p < 0.05), whereas the SFO group reported a 1.5-fold higher frequency of BSS stool types 5-7 (more likely loose stool and diarrhea, not significant). Participants in the SFO group showed a trend toward better adherence to phosphate binder therapy (SFO: 87.6% vs. SEV: 66.6%, not significant). UTOX, serum phosphorus, nutritional and liver function markers, and tryptophan were not different between the two groups. CONCLUSION: There was no difference in the gut microbiome-derived UTOX levels between phosphate binders (SFO vs. SEV), despite SFO therapy resulting in fewer constipated participants. This pilot study may inform study design of future clinical trials and highlights the importance of including factors beyond bowel habits and their association with UTOX levels.

Outcomes of minimally invasive aortic valve replacement in patients with obese body mass indices.

BACKGROUND: Minimally invasive heart valve surgery has previously been shown to be safe and feasible in obese patients. Within this population, we investigated the effect of obesity class on the patient outcomes of minimally invasive aortic valve replacement (mini-AVR). METHODS: A single-center retrospective cohort study of consecutive patients with obese body mass indices (BMIs) who underwent mini-AVR between 2012 and 2020. Patients were stratified into three groups according to Centers for Disease Control and Prevention adult obesity classifications: Class I (BMI: 30.0-<35.0), Class II (BMI: 35.0-<40.0), and Class III (BMI ≥ 40.0). The primary outcomes were postoperative length of stay (LOS), 30-day mortality, and direct cost. RESULTS: Among 206 obese patients who underwent mini-AVR, LOS (Class I 5 [3-7] vs. Class II 6 [5-7] vs. Class III 6 [5-7] days; p = .056), postoperative 30-day mortality (Class I 2.44% [n = 3] vs. Class II 4.44% [n = 2] vs. Class III 7.89% [n = 3]; p = .200), and costs (Class I $24,118 [$20,237-$29.591] vs. Class II $22,215 [$18,492-$28,975] vs. Class III $24,810 [$20,245-$32,942] USD; p = .683) did not differ between obesity class cohorts. CONCLUSIONS: Mini-AVR is safe and feasible to perform for obese patients regardless of their obesity class. Patients with obesity should be afforded the option of minimally invasive aortic valve surgery regardless of their obesity class.

CREG1 promotes lysosomal biogenesis and function.

CREG1 is a small glycoprotein which has been proposed as a transcription repressor, a secretory ligand, a lysosomal, or a mitochondrial protein. This is largely because of lack of antibodies for immunolocalization validated through gain- and loss-of-function studies. In the present study, we demonstrate, using antibodies validated for immunofluorescence microscopy, that CREG1 is mainly localized to the endosomal-lysosomal compartment. Gain- and loss-of-function analyses reveal an important role for CREG1 in both macropinocytosis and clathrin-dependent endocytosis. CREG1 also promotes acidification of the endosomal-lysosomal compartment and increases lysosomal biogenesis. Functionally, overexpression of CREG1 enhances macroautophagy/autophagy and lysosome-mediated degradation, whereas knockdown or knockout of CREG1 has opposite effects. The function of CREG1 in lysosomal biogenesis is likely attributable to enhanced endocytic trafficking. Our results demonstrate that CREG1 is an endosomal-lysosomal protein implicated in endocytic trafficking and lysosomal biogenesis.Abbreviations: AIFM1/AIF: apoptosis inducing factor mitochondria associated 1; AO: acridine orange; ATP6V1H: ATPase H+ transporting V1 subunit H; CALR: calreticulin; CREG: cellular repressor of E1A stimulated genes; CTSC: cathepsin C; CTSD: cathepsin D; EBAG9/RCAS1: estrogen receptor binding site associated antigen 9; EIPA: 5-(N-ethyl-N-isopropyl)amiloride; ER: endoplasmic reticulum; GFP: green fluorescent protein; HEXA: hexosaminidase subunit alpha; IGF2R: insulin like growth factor 2 receptor; LAMP1: lysosomal associated membrane protein 1; M6PR: mannose-6-phosphate receptor, cation dependent; MAPK1/ERK2: mitogen-activated protein kinase 1; MTORC1: mechanistic target of rapamycin kinase complex 1; PDIA2: protein disulfide isomerase family A member 2; SQSTM1/p62: sequestosome 1; TF: transferrin; TFEB: transcription factor EB.

Impact of risk factors on in-hospital mortality for octogenarians undergoing cardiac surgery.

BACKGROUND: Octogenarians undergoing cardiac surgery have higher mortality than their younger counterparts. OBJECTIVES: To determine if various risk factors have the same effect on mortality in octogenarians as in younger patients. METHODS: The National Inpatient Sample data set from 2004 to 2014 was queried to select patients aged 65 years and older who underwent either coronary artery bypass grafting (CABG), valvular heart surgery (VHS), or both (CABG + VHS) within 10 days of hospital admission. The patients were divided into two groups 65-79 years and 80 years and greater. Hospital mortality, patient demographics, comorbidities, and type of hospital admission was evaluated and compared using χ2 and multivariable logistic regressions. RESULTS: About 397,713 patients were identified including 86,345 (21.7%) aged 80 and above. Octogenarians had higher in-hospital mortality for all procedures: CABG (4.94% vs. 2.39%, p < .001), VHS (5.49% vs. 4.08%, p < .001), and CABG + VHS (7.59% vs. 5.95%, p < .001), and this relationship persisted when gender, race, comorbidities, and type of hospital admission were controlled for: CABG (odds ratio [OR] = 1.71; 95% confidence interval [CI] 1.62-1.81); VHS (OR = 1.18; 95% CI 1.11-1.27); and CABH + VHS (OR = 1.17; 95%CI 1.10-1.26). Female gender, renal, or heart failure, nonelective admission, and CABG + VHS were associated with increased risk of in-hospital mortality. Octogenarians had higher rates of these factors (p < .001). The effect size of renal and heart failure and type of surgery was smaller for octogenarians. CONCLUSIONS: Octogenarians undergoing cardiac surgery have higher rates of nonelective admissions, renal and heart failure, and female gender, which are most strongly associated with in-hospital mortality. Differing effect sizes suggest that certain risk factors, such as renal and heart failure, contribute more to mortality in younger patients.

Femoral arterial cannulation remains a safe and reliable option for aortic dissection repair.

BACKGROUND: The optimal cannulation site for repair of type A aortic dissection remains controversial. The concern for Malperfusion syndrome has initiated a national trend away from femoral cannulation to axillary artery and direct ascending aortic cannulation. The purpose of this study was to report a single center experience with femoral artery cannulation for the repair of a type A dissection. METHODS: A retrospective study was performed on 52 patients who underwent surgical repair for a type A dissection between January 1st, 2012 and June 30th, 2019 at a single institution. Of the 52 patients analyzed, 35 (67.3%) underwent femoral artery, 11 (21.2%) direct ascending aortic, and 6 (11%) axillary artery cannulation for arterial access. Deep hypothermic circulatory arrest was used in all the patients. Rates of postoperative complication and mortality were reported. RESULTS: The mortality and bleeding rates for all the patients undergoing repair of the type A dissection repairs were 27% (14/52) and 19% (10/52), respectively. Cardiopulmonary bypass was established in 100% of the patients that had femoral arterial cannulation. There were no complications specifically related to femoral arterial cannulation nor the axillary or direct aortic approach. Specifically, there was no episodes of malperfusion syndrome, bleeding, or injury with femoral artery cannulation. Bleeding rates were higher in cases that proceeded with a femoral (13%) versus alternate (6%) approach however; neither of the bleeding was related to the cannulation site. None of the mortalities identified were directly attributable to the cannulation approach in each case. CONCLUSIONS: Despite the recent shift away from femoral cannulation, the results of the study show that femoral artery cannulation is safe and produces excellent results for establishing cardiopulmonary bypass. The concerns for malperfusion syndrome related to femoral cannulation were not seen.

SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-19.

Background: To date, it is unclear whether SARS-CoV-2 is present in spent dialysate from patients with COVID-19 on peritoneal dialysis (PD). Our aim was to assess the presence or absence of SARS-CoV-2 in spent dialysate from patients on chronic PD who had a confirmed diagnosis of COVID-19. Methods: Spent PD dialysate samples from patients on PD who were positive for COVID-19 were collected between March and August 2020. The multiplexed, real-time RT-PCR assay contained primer/probe sets specific to different SARS-CoV-2 genomic regions and to bacteriophage MS2 as an internal process control for nucleic acid extraction. Demographic and clinical data were obtained from patients' electronic health records. Results: A total of 26 spent PD dialysate samples were collected from 11 patients from ten dialysis centers. Spent PD dialysate samples were collected, on average, 25±13 days (median, 20; range, 10-45) after the onset of symptoms. The temporal distance of PD effluent collection relative to the closest positive nasal-swab RT-PCR result was 15±11 days (median, 14; range, 1-41). All 26 PD effluent samples tested negative at three SARS-CoV-2 genomic regions. Conclusions: Our findings indicate the absence of SARS-CoV-2 in spent PD dialysate collected at ≥10 days after the onset of COVID-19 symptoms. We cannot rule out the presence of SARS-CoV-2 in spent PD dialysate in the early stage of COVID-19.

PTEN dephosphorylates Abi1 to promote epithelial morphogenesis.

The tumor suppressor PTEN is essential for early development. Its lipid phosphatase activity converts PIP3 to PIP2 and antagonizes the PI3K-Akt pathway. In this study, we demonstrate that PTEN's protein phosphatase activity is required for epiblast epithelial differentiation and polarization. This is accomplished by reconstitution of PTEN-null embryoid bodies with PTEN mutants that lack only PTEN's lipid phosphatase activity or both PTEN's lipid and protein phosphatase activities. Phosphotyrosine antibody immunoprecipitation and mass spectrometry were used to identify Abi1, a core component of the WASP-family verprolin homologous protein (WAVE) regulatory complex (WRC), as a new PTEN substrate. We demonstrate that PTEN dephosphorylation of Abi1 at Y213 and S216 results in Abi1 degradation through the calpain pathway. This leads to down-regulation of the WRC and reorganization of the actin cytoskeleton. The latter is critical to the transformation of nonpolar pluripotent stem cells into the polarized epiblast epithelium. Our findings establish a link between PTEN and WAVE-Arp2/3-regulated actin cytoskeletal dynamics in epithelial morphogenesis.

PTEN suppresses epithelial-mesenchymal transition and cancer stem cell activity by downregulating Abi1.

The epithelial-mesenchymal transition (EMT) is an embryonic program frequently reactivated during cancer progression and is implicated in cancer invasion and metastasis. Cancer cells can also acquire stem cell properties to self-renew and give rise to new tumors through the EMT. Inactivation of the tumor suppressor PTEN has been shown to induce the EMT, but the underlying molecular mechanisms are less understood. In this study, we reconstituted PTEN-deficient breast cancer cells with wild-type and mutant PTEN, demonstrating that restoration of PTEN expression converted cancer cells with mesenchymal traits to an epithelial phenotype and inhibited cancer stem cell (CSC) activity. The protein rather than the lipid phosphatase activity of PTEN accounts for the reversal of the EMT. PTEN dephosphorylates and downregulates Abi1 in breast cancer cells. Gain- and loss-of-function analysis indicates that upregulation of Abi1 mediates PTEN loss-induced EMT and CSC activity. These results suggest that PTEN may suppress breast cancer invasion and metastasis via dephosphorylating and downregulating Abi1.