Hypoxia-mediated repression of pyruvate carboxylase drives immunosuppression.

BACKGROUND: Metabolic plasticity mediates breast cancer survival, growth, and immune evasion during metastasis. However, how tumor cell metabolism is influenced by and feeds back to regulate breast cancer progression are not fully understood. We identify hypoxia-mediated suppression of pyruvate carboxylase (PC), and subsequent induction of lactate production, as a metabolic regulator of immunosuppression. METHODS: We used qPCR, immunoblot, and reporter assays to characterize repression of PC in hypoxic primary tumors. Steady state metabolomics were used to identify changes in metabolite pools upon PC depletion. In vivo tumor growth and metastasis assays were used to evaluate the impact of PC manipulation and pharmacologic inhibition of lactate transporters. Immunohistochemistry, flow cytometry, and global gene expression analyzes of tumor tissue were employed to characterize the impact of PC depletion on tumor immunity. RESULTS: PC is essential for metastatic colonization of the lungs. In contrast, depletion of PC in tumor cells promotes primary tumor growth. This effect was only observed in immune competent animals, supporting the hypothesis that repression of PC can suppress anti-tumor immunity. Exploring key differences between the pulmonary and mammary environments, we demonstrate that hypoxia potently downregulated PC. In the absence of PC, tumor cells produce more lactate and undergo less oxidative phosphorylation. Inhibition of lactate metabolism was sufficient to restore T cell populations to PC-depleted mammary tumors. CONCLUSIONS: We present a dimorphic role for PC in primary mammary tumors vs. pulmonary metastases. These findings highlight a key contextual role for PC-directed lactate production as a metabolic nexus connecting hypoxia and antitumor immunity.

Efficacy and safety of catheter-based thrombectomy versus catheter-directed thrombolysis in acute pulmonary embolism.

Data comparing catheter-based thrombectomy (CBT) and catheter-directed thrombolysis (CDT) in acute pulmonary embolism are lacking. To address this, we performed a meta-analysis of prospective and retrospective studies of CBT and compared it to performance goal rates of mortality and major bleeding from a recently published network meta-analysis. When compared with performance goal for CDT based on historical studies, CBT was noninferior for all-cause mortality (6.0% vs 6.87%; P-valueNI < .001), non-inferior and superior for major bleeding (4.9% vs 11%; P-valueNI < .001 and P < .001 for superiority).

Quality and rapidity of anticoagulation in patients with acute pulmonary embolism undergoing mechanical thrombectomy.

The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE.

Percutaneous mechanical thrombectomy in acute pulmonary embolism: Outcomes from a safety-net hospital.

BACKGROUND: Our study aims to present clinical outcomes of mechanical thrombectomy (MT) in a safety-net hospital. METHODS: This is a retrospective study of intermediate or high-risk pulmonary embolism (PE) patients who underwent MT between October 2020 and May 2023. The primary outcome was 30-day mortality. RESULTS: Among 61 patients (mean age 57.6 years, 47% women, 57% Black) analyzed, 12 (19.7%) were classified as high-risk PE, and 49 (80.3%) were intermediate-risk PE. Of these patients, 62.3% had Medicaid or were uninsured, 50.8% lived in a high poverty zip code. The prevalence of normotensive shock in intermediate-risk PE patients was 62%. Immediate hemodynamic improvements included 7.4 mmHg mean drop in mean pulmonary artery pressure (-21.7%, p < 0.001) and 93% had normalization of their cardiac index postprocedure. Thirty-day mortality for the entire cohort was 5% (3 patients) and 0% when restricted to the intermediate-risk group. All 3 patients who died at 30 days presented with cardiac arrest. There were no differences in short-term mortality based on race, insurance type, citizenship status, or socioeconomic status. All-cause mortality at most recent follow up was 13.1% (mean follow up time of 13.4 ± 8.5 months). CONCLUSION: We extend the findings from prior studies that MT demonstrates a favorable safety profile with immediate improvement in hemodynamics and a low 30-day mortality in patients with acute PE, holding true even with relatively higher risk and more vulnerable population within a safety-net hospital.

Socioeconomic Disparities in Anal Cancer: Effect on Treatment Delay and Survival.

BACKGROUND: Socioeconomic inequities have implications for access to health care and may be associated with disparities in treatment and survival. OBJECTIVE: To investigate the impact of socioeconomic inequities on time to treatment and survival of anal squamous-cell carcinoma. DESIGN: This is a retrospective study using a nationwide data set. SETTINGS: The patients were selected from the National Cancer Database and enrolled from 2004 to 2016. PATIENTS: We identified patients with stage I to III squamous-cell carcinoma of the anus who were treated with chemoradiation therapy. MAIN OUTCOMES MEASURES: Socioeconomic factors, including race, insurance status, median household income, and percentage of the population with no high school degrees, were included. The association of these factors with treatment delay and overall survival was investigated. RESULTS: A total of 24,143 patients who underwent treatment for grade I to III squamous-cell carcinoma of the anus were identified. The median age was 60 years, and 70% of patients were women. The median time to initiation of treatment was 33 days. Patients from zip codes with lower median income, patients with a higher percentage of no high school degree, and patients with other government insurance followed by Medicaid insurance had treatment initiated after 60 days from diagnosis. Kaplan-Meier survival analysis showed that the late-treatment group had worse overall survival compared to the early treatment group (98 vs 125 months; p < 0.001). LIMITATIONS: No detailed information is available about the chemoradiotherapy regimen, completion of treatment, recurrence, disease-free survival, and individual-level socioeconomic condition and risk factors. CONCLUSION: Patients from communities with lower median income, level of education, and enrolled in public insurance had longer time to treatment. Lower socioeconomic status was also associated with poorer overall survival. These results warrant further analysis and measures to improve access to care to address this disparity. See Video Abstract . DESIGUALDADES SOCIOECONMICAS EN CASOS DE CNCER ANAL EFECTOS EN EL RETRASO DEL TRATAMIENTO Y LA SOBREVIDA: ANTECEDENTES:Las desigualdades socio-económicas tienen implicaciones en el acceso a la atención médica y pueden estar asociadas con disparidades en el tratamiento y la sobrevida.OBJETIVO:Indagar el impacto de las desigualdades socio-económicas sobre el tiempo de retraso en el tratamiento y la sobrevida en casos de carcinoma a células escamosas del ano (CCEA).DISEÑO:Estudio retrospectivo utilizando un conjunto de datos a nivel nacional.AJUSTES:Todos aquellos pacientes inscritos entre 2004 a 2016 y que fueron seleccionados de la Base Nacional de Datos sobre el Cáncer.PACIENTES:Identificamos pacientes con CCEA en estadíos I-III y que fueron tratados con radio-quimioterápia.PRINCIPALES MEDIDAS DE RESULTADOS:Se incluyeron factores socio-económicos tales como la raza, el tipo de seguro de salud, el ingreso familiar medio y el porcentaje de personas sin bachillerato de secundaria (SBS). Se investigó la asociación entre estos factores con el retraso en iniciar el tratamiento y la sobrevida global.RESULTADOS:Se identificaron un total de 24.143 pacientes que recibieron tratamiento para CCEA estadíos I-III. La mediana de edad fue de 60 años donde 70% eran de sexo femenino. La mediana del tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue de 33 días. Los pacientes residentes en zonas de código postal con ingresos medios más bajos, con un mayor porcentaje de individuos SBS y los pacientes con otro tipo de seguro gubernamental de salud, seguidos del seguro tipo Medicaid iniciaron el tratamiento solamente después de 60 días al diagnóstico inicial de CCEA. El análisis de Kaplan-Meier de la sobrevida mostró que el grupo de tratamiento tardío tuvo una peor supervivencia general comparada con el grupo de tratamiento precoz o temprano (98 frente a 125 meses; p <0,001).LIMITACIONES:No se dispone de información detallada sobre el tipo de radio-quimioterapia utilizada, ni sobre la finalización del tratamiento o la recurrencia, tampoco acerca de la sobrevida libre de enfermedad ni sobre las condiciones socio-económicas o aquellos factores de riesgo a nivel individual.CONCLUSIÓN:Los pacientes de comunidades con ingresos medios más bajos, con un nivel de educación limitado e inscritos en un seguro público tardaron mucho más tiempo en recibir el tratamiento prescrito. El nivel socio-económico más bajo también se asoció con una sobrevida global más baja. Los presentes resultados justifican mayor análisis y medidas mas importantes para mejorar el acceso a la atención en salud y poder afrontar esta disparidad. (Traducción-Dr. Xavier Delgadillo ).

Updates in the Management of Paraneoplastic Syndrome.

Paraneoplastic neurological syndromes (PNS) are defined as remote neurologic immune-mediated effects triggered by underlying systemic tumors. While recognizing specific syndromes can aid early cancer detection, overutilization of paraneoplastic assays in the absence of a classic syndrome can precipitate overdiagnosis and overtreatment. PNS involve autoantibodies targeting intracellular or extracellular antigens, with variable immunotherapy responses based on antigen type. Diagnosing PNS is challenging, requiring exclusion of other differential diagnoses. New diagnostic criteria classify PNS into high-risk and intermediate-risk phenotypes based on clinical phenotype, neuronal antibodies, and cancer presence. Patients with cell surface antibodies respond better to immunotherapies compared to those with intracellular antigen targets. Understanding PNS syndromes, serological markers, and oncological features guides management, which facilitates initiation of immunosuppression for PNS alongside treatment of the underlying neoplasm, thereby improving neurologic and oncologic outcomes. Initial treatments often include intravenous methylprednisolone, plasma exchange, or intravenous immunoglobulins. Second-line immunosuppressants like rituximab or cyclophosphamide may be necessary if initial treatments fail. Specific therapies vary based on antibody target. Here, we summarize the current approach to the investigation, diagnosis, and treatment of patients with suspected PNS.

The economic and societal impact of periodontal and peri-implant diseases.

Periodontal and peri-implant diseases result from a chronic inflammatory response to dysbiotic microbial communities and are characterized by inflammation in the soft tissue and the ensuing progressive destruction of supporting bone, resulting in tooth or implant loss. These diseases' high prevalence, multifactorial etiology, extensive treatment costs, and significant detriment to patients' quality-of-life underscore their status as a critical public health burden. This review delineates the economic and sociocultural ramifications of periodontal and peri-implant diseases on patient welfare and healthcare economics. We delve into the implications of diagnosis, treatment, supportive care, and managing destructive tissue consequences, contrasting these aspects with healthy patients.

Root surface biomodification in periodontal therapy: Biological rationale and clinical applications.

Regenerative periodontal therapy aims to form new cementum, periodontal ligament, and alveolar bone, all sealed by gingival tissue. The root surface acts as the wound margin during this regeneration process. Root surface biomodification (root conditioning/root decontamination), therefore, seems instrumental in promoting surface decontamination and enhancing tissue attachment by removing the smear layer, exposing collagen fibrils, and facilitating blood clot formation and stabilization. This review attempted to provide an all-encompassing, evidence-based assessment of the role of root surface biomodification in regenerative periodontal therapy, particularly in intrabony defects, furcation defects, and root coverage procedures. The reviewed evidence suggested that root conditioning agents, whether used independently or in conjunction with bone graft materials, biological agents, membranes, or connective tissue grafts, do not offer any clinical advantage regarding clinical attachment gain. Thus, integrating chemical methods with the mechanical root instrumentation process does not necessarily contribute to superior clinical outcomes.

Association between asthma and periodontitis: A case-control analysis of risk factors, related medications, and allergic responses.

AIMS: This study aimed to investigate the association between asthma, related allergies and medication use, and the presence and severity of periodontitis among individuals at the University of Michigan School of Dentistry. METHODS: Employing a case-control design, the study analyzed data from 892 patients, half with asthma and half without asthma. Data collection included demographics, asthma history, medication use, allergies, and periodontal examination outcomes, including probing pocket depth (PPD), mobility, furcation involvement, and radiographic bone loss (RBL). Logistic regression models assessed the relationship between asthma and periodontitis, adjusting for confounders. RESULTS: Asthmatic patients exhibited significantly lower odds of periodontitis (OR = 0.10, p < .001) and were less likely to present with advanced stages (OR = 0.23, p < .001) and grades of the disease (OR = 0.31, p < .001) compared to non-asthmatic patients. The study also found a higher proportion of females in the asthmatic group (67% vs. 51.8%, p < .001). Smoking was identified as a significant factor associated with periodontitis in patients with asthma, with former smokers at more than double the odds (OR = 2.28, p = .035) and current smokers at a slightly lower yet significant odds (OR = 1.87, p = .050). Additionally, asthmatic patients on adrenergic inhalers had an increased likelihood of developing periodontitis (OR = 1.76, p = .045). Allergies to codeine and latex were associated with higher odds of periodontitis, with ORs of 3.41 and 6.09, respectively. CONCLUSIONS: Asthma was found to be associated with lower odds of periodontitis. However, this association appears to be modified by smoking habits and the use of certain asthma medications, which are related to an increased likelihood of periodontitis among asthmatic patients.

Intracellular mechanics and TBX3 expression jointly dictate the spreading mode of melanoma cells in 3D environments.

Cell stiffness and T-box transcription factor 3 (TBX3) expression have been identified as biomarkers of melanoma metastasis in 2D environments. This study aimed to determine how mechanical and biochemical properties of melanoma cells change during cluster formation in 3D environments. Vertical growth phase (VGP) and metastatic (MET) melanoma cells were embedded in 3D collagen matrices of 2 and 4 mg/ml collagen concentrations, representing low and high matrix stiffness. Mitochondrial fluctuation, intracellular stiffness, and TBX3 expression were quantified before and during cluster formation. In isolated cells, mitochondrial fluctuation decreased and intracellular stiffness increased with increase in disease stage from VGP to MET and increased matrix stiffness. TBX3 was highly expressed in soft matrices but diminished in stiff matrices for VGP and MET cells. Cluster formation of VGP cells was excessive in soft matrices but limited in stiff matrices, whereas for MET cells it was limited in soft and stiff matrices. In soft matrices, VGP cells did not change the intracellular properties, whereas MET cells exhibited increased mitochondrial fluctuation and decreased TBX3 expression. In stiff matrices, mitochondrial fluctuation and TBX3 expression increased in VGP and MET, and intracellular stiffness increased in VGP but decreased in MET cells. The findings suggest that soft extracellular environments are more favourable for tumour growth, and high TBX3 levels mediate collective cell migration and tumour growth in the earlier VGP disease stage but play a lesser role in the later metastatic stage of melanoma.

Periodontitis stage and grade modifies the benefit of regular supportive periodontal care in terms of need for retreatment and mean cumulative cost.

AIM: This study aimed to characterize the periodontal breakdown during supportive periodontal care (SPC) and to quantify the corresponding cost-effectiveness of periodontal therapy. MATERIALS AND METHODS: Data were obtained from charts of patients who received active periodontal therapy (APT) with a minimum follow-up of ≥10 years. Analysis was done to identify factors associated with the incidence of additional sub-gingival instrumentation (SGI) and/or surgery (SUR) during SPC and mean cumulative cost of recurrence was calculated. All relevant data were collected. RESULTS: In all, 442 patients were included. Over the follow-up period, 62% of Stage I and II patients and 72% of Stage III and IV patients required further treatment following the APT; 56.5% of SGI patients and 78.6% of SUR patients received a second intervention. SUR patients received more SUR during the follow-up period (p = .035). Stage III and IV patients received more SUR during SPC than Stage I and II patients (p = .001). Grade C patients received more SUR during the follow-up period (p < .05). During the 5-year period preceding retreatment, the mean SPC visits were lower for patients who did not require retreatment (p < .001). Risk factors such as regularity of maintenance, smoking and diabetes were related to a higher chance of receiving SUR during the follow-up period (p < .05). The mean cumulative costs indicated less recurrence cost for compliers in Stage III and IV or Grade B and C but not for those in Stage I and II or Grade A. CONCLUSIONS: The risk of relapse in the maintenance population may be correlated with higher stage and grade, patient compliance, modifiable risk factors and the nature of the treatment provided during APT. The total cost of treatment of recurrences was lower for compliers in Stage III/IV and Grade B/C compared with erratic compliers with the same severity and risk.

Short (≤6 mm) compared with ≥10-mm dental implants in different clinical scenarios: A systematic review of randomized clinical trials with meta-analysis, trial sequential analysis and quality of evidence grading.

AIM: To systematically identify, synthesize and critically summarize the available scientific evidence from randomized controlled trials (RCTs) regarding whether short (≤6 mm) perform as well as long (≥10 mm) implants regarding implant survival, marginal bone loss, and biologic and prosthetic complications in different clinical scenarios. MATERIALS AND METHODS: Cochrane Collaboration's risk of bias tool and the GRADE approach were applied. Results were synthesized using random-effects meta-analyses assessed by trial sequential analyses. RESULTS: Forty reports on 19 RCTs comprising 2214 (1097 short; 1117 long) implants were included. Moderate/high certainty/quality evidence demonstrated similar 5-year survival rates for ≤6-mm and ≥10-mm implants in non-augmented bone and full-mouth rehabilitation in either jaw, and for 6-mm implants in the maxilla instead of sinus lift. Nevertheless, the evidence for 5-year survival rates remains inconclusive or insufficient for the remaining combinations of implant lengths and clinical scenarios. They include 4-mm and 5-mm implants as alternatives to sinus lift as well as placing all implant lengths ≤6 mm instead of vertical ridge augmentation with long implants. Marginal bone level and short- and long-term biologic or prosthetic complications were similar. CONCLUSIONS: Based on moderate/high certainty/quality evidence from 5-year RCTs, implants ≤6 mm may be viable alternatives to ≥10-mm implants in either jaw in native bone and full-arch rehabilitation, and 6-mm implants may be used as an alternative to sinus lift. TRIAL REGISTRATION: PROSPERO ID: CRD42021254365.

Clinical outcomes of implant- versus abutment-level connection in screw-retained fixed dental prostheses: A 5-year randomized controlled trial.

AIM: The aim of the study was to evaluate the 5 years clinical outcomes associated with implant-level connection (IL) versus abutment-level connection (AL) for implants with an internal conical connection (ICC) supporting a screw-retained fixed partial denture. MATERIALS AND METHODS: Fifty patients with 119 implants were randomly allocated to either the AL or IL group. Radiographic (Marginal bone loss) and clinical outcomes (Bleeding on Probing, probing pocket depth, plaque accumulation, incidence of peri-implantitis and peri-implant mucositis as well as prosthetic complications) were collected and compared at 1, 2, 3, and 5 years. A linear mixed model was used to evaluate the differences between groups. RESULTS: Five years after treatment, the MBL change was not significantly different between the groups at any point. The MBL was 0.23 ± 0.64 mm (AL) and 0.23 ± 0.29 mm (IL). The bleeding on Probing was 44% (AL) and 45% (IL) (p = .89). The mean probing depth was 2.91 ± 1.01 mm (AL) and 3.51 ± 0.67 mm (IL). This difference between the groups was statistically significant but clinical insignificant. Presence of plaque was slightly higher (p = .06) in the IL group (34.4%) compared with the AL group (26.3%). The overall technical, biological, and prosthetic complication rates were similar between groups. None of the implants developed peri-implantitis during the entire follow-up period. CONCLUSION: The results of this clinical trial indicated that all clinical and radiographical parameters were clinically comparable between the study groups.

Factors associated with furcation involvement and fixed prostheses: A cross-sectional study.

OBJECTIVE: The study aims to explore the relationship between horizontal and vertical furcation involvement (FI) in teeth with or without a single unit fixed prosthesis (FP). MATERIALS AND METHODS: Adult subjects presenting to the periodontics department requiring cone beam computed tomography (CBCT) analysis were recruited for this study. 79 patients, with a total of 200 teeth, were split into two groups based on the presence or absence of FP within the same patient. Our analysis considered patient-level factors like smoking, diabetes, and periodontal severity and tooth-level factors including root trunk length (RTL), probing depth (PD), periodontal supracrestal tissue height (STH), supracrestal tissue attachment (STH-PD), interproximal bone distance (IPBD) to the cementoenamel junction (CEJ) (control) or crown margin (Test), and the distance from the furcation to the CEJ (control) or crown margin (Test). Subsequently, we developed a predictive model for FI. RESULTS: The presence of a prosthesis had a significant association with FI, with an odds ratio (OR) of 12.8 (p < 0.001). Other factors significantly correlated with FI were periodontitis (OR = 10.9; p = 0.006), buccal furcation site (OR = 5.70; p < 0.001), and PD (OR = 1.90; p = 0.027). FP placement increased IPBD by 1.08 mm (p < 0.001). The predictive model built for FI demonstrated a sensitivity of 92.9% and a specificity of 66.7%. CONCLUSIONS: Fixed prosthesis significantly influenced FI only in periodontitis patients. Factors such as periodontitis Stage, probing depth, and buccal site contribute to FI. The high sensitivity of the predictive model highlights the importance of considering these correlations during treatment planning. CLINICAL RELEVANCE: Comprehending FI factors is vital for devising customised treatment plans to halt disease progression and enhance outcomes of periodontal regenerative therapies.

Recommendations for successful virtual patient-assisted esthetic implant rehabilitation: A guide for optimal function and clinical efficiency.

OBJECTIVE: Complete arch implant rehabilitation necessitates meticulous treatment planning and high-level collaboration between surgical and prosthetic dental teams. Emerging virtual technologies hold considerable promise in streamlining this process. The aim of this article is to extend recommendations to clinicians venturing into the virtual patient-assisted esthetic implant rehabilitation workflow. OVERVIEW: This article summarizes recommendations for virtual patient-assisted esthetic implant rehabilitation in the following five aspects: three-dimensional data handling and superimposition, occlusion and virtual articulator integration in creating virtual patients, streamlined face- and prosthetic-driven surgical planning, reuse of presurgical data ("Copy & Paste"), and final impression for passive fitting of final restoration. To illustrate these principles, a case with complete-mouth implant rehabilitation completed within six visits using this virtual patient workflow is presented. CONCLUSION: The virtual patient workflow serves as an invaluable tool to perform treatment planning, enhance efficiency, and ensure predictable outcomes in esthetic complete arch implant rehabilitation. CLINICAL SIGNIFICANCE: Virtual workflows are increasingly prevalent in esthetic implant rehabilitation. Nevertheless, these workflows necessitate a distinct set of knowledge and tools divergent from conventional dentistry practices. This article offers guidelines and recommendations for dental clinicians who are new to this field.

Minimally invasive periodontal regeneration with the buccal approach: a systematic review and meta-analysis of clinical studies.

OBJECTIVE: The aim of this study was to investigate clinical periodontal parameters after treatment using the Minimally Invasive Surgical Technique (MIST), Modified Minimally Invasive Surgical Technique (M-MIST), and/or any technique for papilla preservation, such as Entire Papilla Preservation (EPP), modified-papilla preservation technique (M-PPT), or simplified-papilla preservation technique (SPPT). METHODS: The focus question was "For patients with periodontal intrabony defects (P), what is the best minimally invasive regenerative approach (I), comparing MIST, M-MIST, and papilla preservation techniques' outcomes (C) to improve PD, CAL, GR, and periodontal stability (O)?" An online search was conducted on PubMed, Cochrane Library, and Embase. Only randomized clinical trials and case series with a minimum of 10 enrolled patients were included. The risk of bias was evaluated using the Critical Appraisal tools in JBI Systematic Reviews. The meta-analysis compared the data obtained for the periodontal parameters analyzed, and the heterogeneity was verified. RESULTS: After the screening, nine articles were included. Seven studies applied MIST and its modifications; two used M-PPT, one SPPT, and one approached EPP. A general statistically significant PD reduction and CAL gain were noted between the groups, comparing baseline and follow-up for all articles, independently of the technique or materials used. Also, all studies showed a non-significant increase in the gingival recession. Four studies had a low risk of bias, four had a moderate risk, and only 1 had a high risk. Moderate heterogeneity was found in one analysis for CAL (65.73%); moderate and substantial heterogeneity was found in the PD results (71.91% and 89.19%); and no heterogeneity was found within all analyses for gingival recession (0%). CONCLUSION: MIST, M-MIST, and papilla preservation techniques demonstrated their potential and efficacy to improve periodontal conditions of sites with intrabony defects with minimal morbidity.

Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation.

Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO 2 ) to assess risk factors for waitlist mortality and post-LT survival. Among 3082 pediatric LT recipients included in the study, 124 patients (4%) received MELD/PELD exception points for HPS. Patients with HPS were a median age of 9 years (interquartile range: 6, 12 years), 54.8% were girls, and 54% were White. Most patients (87.9%) were listed with laboratory MELD/PELD scores <15. Waitlist mortality for patients with HPS exception points was rare and not different from patients without HPS. When stratified by pre-LT PaO 2 , hypoxemia severity was not associated with differences in 1-, 3-, or 5-year survival rates after LT ( p = 0.13). However, patients with HPS showed a slightly lower survival rate at 5 years compared with patients without HPS (88.7% vs. 93.4%; p = 0.04). MELD/PELD exceptions for children with HPS mitigated waitlist mortality, and recipients with HPS experienced excellent 5-year survival after LT, although slightly lower than in patients without HPS. Unlike adults with HPS, the severity of pre-LT hypoxemia in children does not impact post-LT survival. These data suggest that adult criteria for granting MELD/PELD exception points may not appropriately capture HPS severity in pediatric patients. Further prospective multicenter studies to examine the risk factors predicting negative survival outcomes in children with HPS are warranted.

Predictors and outcomes of acute pulmonary embolism in COVID-19; insights from US National COVID cohort collaborative.

OBJECTIVES: To investigate whether COVID-19 patients with pulmonary embolism had higher mortality and assess the utility of D-dimer in predicting acute pulmonary embolism. PATIENTS AND METHODS: Using the National Collaborative COVID-19 retrospective cohort, a cohort of hospitalized COVID-19 patients was studied to compare 90-day mortality and intubation outcomes in patients with and without pulmonary embolism in a multivariable cox regression analysis. The secondary measured outcomes in 1:4 propensity score-matched analysis included length of stay, chest pain incidence, heart rate, history of pulmonary embolism or DVT, and admission laboratory parameters. RESULTS: Among 31,500 hospitalized COVID-19 patients, 1117 (3.5%) patients were diagnosed with acute pulmonary embolism. Patients with acute pulmonary embolism were noted to have higher mortality (23.6% vs.12.8%; adjusted Hazard Ratio (aHR) = 1.36, 95% CI [1.20-1.55]), and intubation rates (17.6% vs. 9.3%, aHR = 1.38[1.18-1.61]). Pulmonary embolism patients had higher admission D-dimer FEU (Odds Ratio(OR) = 1.13; 95%CI [1.1-1.15]). As the D-dimer value increased, the specificity, positive predictive value, and accuracy of the test increased; however, sensitivity decreased (AUC 0.70). At cut-off D-dimer FEU 1.8 mcg/ml, the test had clinical utility (accuracy 70%) in predicting pulmonary embolism. Patients with acute pulmonary embolism had a higher incidence of chest pain and history of pulmonary embolism or deep vein thrombosis. CONCLUSIONS: Acute pulmonary embolism is associated with worse mortality and morbidity outcomes in COVID-19. We present D-dimer as a predictive risk tool in the form of a clinical calculator for the diagnosis of acute pulmonary embolism in COVID-19.

Overview of fermentation process: structure-function relationship on protein quality and non-nutritive compounds of plant-based proteins and carbohydrates.

Demands for high nutritional value-added food products and plant-based proteins have increased over the last decade, in line with the growth of the human population and consumer health awareness. The quality of the plant-based proteins depends on their digestibility, amino acid content, and residues of non-nutritive compounds, such as phenolic compounds, anti-nutritional compounds, antioxidants, and saponins. The presence of these non-nutritive compounds could have detrimental effects on the quality of the proteins. One of the solutions to address these shortcomings of plant-based proteins is fermentation, whereby enzymes that present naturally in microorganisms used during fermentation are responsible for the cleavage of the bonds between proteins and non-nutritive compounds. This mechanism has pronounced effects on the non-nutritive compounds, resulting in the enhancement of protein digestibility and functional properties of plant-based proteins. We assert that the types of plant-based proteins and microorganisms used during fermentation must be carefully addressed to truly enhance the quality, functional properties, and health functionalities of plant-based proteins.Supplemental data for this article is available online at here. show.

Characterization of Balance Control and Postural Stability in Patients With Alzheimer Disease.

Balance in Alzheimer disease (AD) patients is not rigorously understood. In this study, we characterize balance using qualitative [Berg Balance Scale (BBS)] and quantitative measures (posturography) and assess relationships between qualitative and quantitative balance measures in AD. Patients with mild-moderate AD (n=48) were recruited. BBS scores and posturography metrics, including medial-lateral sway range, anterior-posterior sway range, sway area, and sway velocity, were assessed in eyes-open and eyes-closed conditions. Adjusted linear regressions were used to assess relationships between posturography and BBS score. Mean BBS score was 50.4±5.3. In eyes-open conditions, posturography and BBS score were not significantly associated. In eyes-closed conditions, better BBS score was significantly associated with lower sway area (ß=-0.91; P =0.006). Better scores of BBS items involving turning and reduced base of support were associated with greater eyes-closed sway area. Posturography in the more challenging eyes-closed condition may predict functional balance deficits in AD patients.