Transforaminal pulsed radiofrequency and epidural steroid injection on chronic lumbar radiculopathy: A prospective observational study from a tertiary care hospital in Vietnam.

BACKGROUND: Lumbosacral radicular syndrome (LRS) is probably the most frequent neuropathic pain syndrome, exaggerating medical and economy burden on developing countries, such as Vietnam. As a result, the urgence to find an approach which is both affordable and effective always puts great demand on medical researchers. OBJECTIVES: Evaluate the effectiveness of transforaminal pulsed radiofrequency (PRF) stimulation on the dorsal root ganglion (DRG) and epidural steroid injection (ESI) in management of chronic lumbosacral radiculopathy. METHODS: Seventy-six patients with chronic radicular pain were performed transforaminal PRF + ESI by neurosurgeons. Demographic characteristics and surgical outcomes were recorded on admission, pre-procedural and post-procedural for 1-month, 3-month, 6-month and 12-month follow-up. Primary outcome was measured by using Visual Analogue Scale (VAS), Oswestry disability index (ODI) and Straight Leg Raising Test (SLRT). Secondary outcome was subjectively collected based on short assessment of patients' satisfaction (SAPS). RESULTS: Patients who received transforaminal PRF and ESI showed significant improvements on all three evaluation tools (VAS, ODI, SLRT), compared to that before treatment (p<0.001). Pain relief was achievable and long-lasting, which met patients' expectation. No significant complications were observed for 12 months follow-up. CONCLUSION: Transforaminal PRF combined with ESI in management of lumbosacral radiculopathy should be a good method of choice for its effectiveness and safety in management of pain.

Intracellular Pseudomonas aeruginosa within the Airway Epithelium of Cystic Fibrosis Lung Tissues.

RATIONALE: Pseudomonas aeruginosa (P.a.) is the major bacterial pathogen colonizing the airways of adult cystic fibrosis (CF) patients and causes chronic infections that persist despite antibiotic therapy. Intracellular bacteria may represent an unrecognized reservoir of bacteria that evades the immune system and antibiotic therapy. While the ability of P.a. to invade and survive within epithelial cells has been described in vitro in different epithelial cell models, evidence of this intracellular lifestyle in human lung tissues is currently lacking. OBJECTIVES: To detect and characterize intracellular P.a. in CF airway epithelium from human lung explant tissues. METHODS: We sampled the lung explant tissues from CF patients undergoing lung transplantation and non-CF lung donor control. We analyzed lung tissue sections for the presence of intracellular P.a. by quantitative culture and microscopy, in parallel to histopathology and airway morphometry. MEASUREMENTS AND MAIN RESULTS: P.a. was isolated from the lungs of 7 CF patients undergoing lung transplantation. Microscopic assessment revealed the presence of intracellular P.a. within airway epithelial cells in 3 out of the 7 patients analyzed, at a varying but low frequency. We observed those events occurring in lung regions with high bacterial burden. CONCLUSION: This is the first study describing the presence of intracellular P.a. in CF lung tissues. While intracellular P.a. in airway epithelial cells are likely relatively rare events, our findings highlight the plausible occurrence of this intracellular bacterial reservoir in chronic CF infections.

The Correlation Between Glycation Gap and Renal Complications in Patients with Type 2 Diabetes Mellitus.

Purpose: The aim of this study was to investigate the correlations between the glycation gap (GG) and renal complications such as urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus patients. Materials and Methods: A cross-sectional study was conducted on 104 individuals (52 males and 52 females), aged 36-93 years old. Fasting blood glucose (FBG), HbA1c, and serum fructosamine were measured simultaneously. GG was calculated as the difference between the measured and fructosamine-based predicted HbA1c levels (FHbA1c). Results: There was a moderately positive correlation between HbA1c and fructosamine concentration (r = 0.488; p < 0.001). GG was positively correlated with UACR (r = 0.3275; p = 0.0007), negatively correlated with eGFR (r = -0.3400; p = 0.0004). HbA1c was positively correlated with UACR (r = 0.2437; p = 0.0127) but not correlated with eGFR (r = -0.444; p = 0.6542). Fructosamine has a positive correlation with eGFR (r = 0.2426; p = 0.0131) but not with UACR (r = -0.1021; p = 0.3025). Conclusion: GG was positively correlated with UACR and inversely correlated with eGFR in type 2 Diabetes mellitus patients. This suggests that GG is a valuable index for predicting kidney complications due to diabetes.

Titanium-Dioxide-Nanoparticle-Embedded Polyelectrolyte Multilayer as an Osteoconductive and Antimicrobial Surface Coating.

Bioactive surface coatings have retained the attention of researchers and physicians due to their versatility and range of applications in orthopedics, particularly in infection prevention. Antibacterial metal nanoparticles (mNPs) are a promising therapeutic, with vast application opportunities on orthopedic implants. The current research aimed to construct a polyelectrolyte multilayer on a highly porous titanium implant using alternating thin film coatings of chitosan and alginate via the layer-by-layer (LbL) self-assembly technique, along with the incorporation of silver nanoparticles (AgNPs) or titanium dioxide nanoparticles (TiO2NPs), for antibacterial and osteoconductive activity. These mNPs were characterized for their physicochemical properties using quartz crystal microgravimetry with a dissipation system, nanoparticle tracking analysis, scanning electron microscopy, and atomic force microscopy. Their cytotoxicity and osteogenic differentiation capabilities were assessed using AlamarBlue and alkaline phosphatase (ALP) activity assays, respectively. The antibiofilm efficacy of the mNPs was tested against Staphylococcus aureus. The LbL polyelectrolyte coating was successfully applied to the porous titanium substrate. A dose-dependent relationship between nanoparticle concentration and ALP as well as antibacterial effects was observed. TiO2NP samples were also less cytotoxic than their AgNP counterparts, although similarly antimicrobial. Together, these data serve as a proof-of-concept for a novel coating approach for orthopedic implants with antimicrobial and osteoconductive properties.

The essential role of non-steroidal anti-inflammatory drugs in pain control following robotic thoracoscopic lung resections.

Background: Enhanced recovery after thoracic surgery (ERATS) protocols use a combination of analgesics for pain control. We investigated the effect of non-steroidal analgesic drugs (NSAIDs) on pain control by comparing patient levels and opioid requirements after robotic pulmonary resections. Methods: We retrospectively analyzed our prospectively maintained institutional database for elective, opioid-naïve robotic thoracoscopic pulmonary resections. All patients received postoperative NSAIDs unless contraindicated or at the discretion of the attending surgeons. Our original protocol (ERATS-V1) was modified to optimize opioid-sparing effect without affecting pain control (ERATS-V2). Demographics, operative outcomes, and postoperative opioid dispensed [morphine milligram equivalent (MME)] were collected. Results: A total of 491 patients (147 ERATS-V1; 344 ERATS-V2) were included in this study. There was no difference in patient characteristics or operative outcomes between ERATS cohorts. Protocol optimization was associated with a 2- to 10-fold reduction of postoperative opioid use without compromising pain control. In ERATS-V1 cohort, there was no difference in pain levels and opioid requirements with NSAID usage. In ERATS-V2 cohort, while pain levels were similar, higher in-hospital opioid consumption was observed in no-NSAID subgroup {MME: 20.5 [interquartile range (IQR), 4.8-40.5] vs. 12.0 (IQR, 2.0-32.2), P=0.0096, schedule II: 14.2 (IQR, 3.0-36.4) vs. 6.8 (IQR, 1.4-24.0), P=0.012} as well as total postoperative schedule II opioid requirement [17.8 (IQR, 3.0-43.5) vs. 8.8 (IQR, 1.5-30), P=0.032]. Conclusions: The opioid-sparing effect of NSAIDs was observed only in optimized ERATS patients. Modifications of our pre-existing ERATS was associated with a significant reduction of opioid consumption without affecting pain levels. This revealed the role of NSAIDs in postoperative pain management otherwise masked by excessive opioids use.

Extracorporeal membrane oxygenation in the surgical management of large mediastinal masses: a narrative review.

Background and Objective: The management of large mediastinal tumors requires a complex multidisciplinary approach, particularly in the perioperative setting due to increased risk of hemodynamic compromise. The utilization of extracorporeal membrane oxygenation (ECMO) provides a useful adjunct in the surgical management for biopsy and resection of these mediastinal masses. The objective of this article is to review indications and implementation of ECMO in the surgical management of mediastinal disease. Methods: A literature review of the PubMed database was completed evaluating articles discussing 'extracorporeal circulation', 'cardiopulmonary bypass', 'anesthesia', 'mediastinal disease', and 'mediastinal cancer'. These articles were evaluated for contribution to the discussion of indications and implementation of ECMO in the management of these patients. Key Content and Findings: Large mediastinal tumors place patients at risk of hemodynamic collapse on induction of anesthesia due to compression of vascular structures, tracheobronchial tree and creation of V/Q mismatch. Patients may be stratified regarding their risk of perioperative complications by evaluation of postural symptoms, cross sectional imaging findings and pulmonary function tests. Those patients at elevated perioperative risk may benefit from the utilization of ECMO, most commonly veno-arterial (V-A) ECMO. Guidewires or ECMO cannulas may be placed under local anesthesia prior to induction. Those patients with hemodynamic compromise may receive mechanical circulatory support to allow completion of the operation. Conclusions: The use of a multidisciplinary team consisting of surgeons, anesthesiologists, perfusionists and OR team is critical to the success in the use of ECMO in the resection of mediastinal masses. With diligent preparation, these high-risk patients may be optimally managed at the time of resection.

Achieving opioid-free discharge following robotic thoracic surgery: A single-institution experience.

Objectives: Enhanced recovery after thoracic surgery (ERATS) protocols use a combination of analgesics for pain control and have been associated with decreased opioid requirements. We investigated the impact of continual ERATS refinement on the incidence of opioid-free discharge. Methods: We retrospectively analyzed our prospectively maintained institutional database for elective, opioid-naive robotic thoracoscopic procedures. Demographics, operative outcomes, postoperative opioid dispensed (morphine milligram equivalent), and opioid discharge status were collected. Our primary outcome of interest was factors associated with opioid-free discharge; our secondary objective was to determine the incidence of new persistent opioid users. Results: In total, 466 patients from our optimized ERATS protocol were included; 309 (66%) were discharged without opioids. However, 34 (11%) of patients discharged without opioids required a prescription postdischarge. Conversely, 7 of 157 patients (11%), never filled their opioid prescriptions given at discharge. Factors associated with opioid-free discharges were nonanatomic resections, mediastinal procedures, minimal pain, and lack of opioid usage on the day of discharge. More importantly, 3.2% of opioid-free discharge patients became new persistent opioid users versus 10.8% of patients filling opioid prescriptions after discharges (P = .0013). Finally, only 2.3% of opioid-naive patients of the entire cohort became chronic opioid users; there was no difference in the incidence of chronic use by opioid discharge status. Conclusions: Optimized opioid-sparing ERATS protocols are highly effective in reducing opioid prescription on the day of discharge. We observed a very low rate of new persistent or chronic opioid use in our cohort, further highlighting the role ERATS protocols in combating the opioid epidemic.

Bronchogenic cysts: a narrative review.

Background and Objective: Bronchogenic cysts represent a rare form of cystic malformation of the respiratory tract. Primarily located in the mediastinum if occurring early in gestation as opposed to the thoracic cavity if arising later in development. However, they can arise from any site along the foregut. They exhibit a variety of clinical and radiologic presentations, representing a diagnostic challenge, especially in areas with endemic hydatid disease. Endoscopic drainage has emerged as a diagnostic and potentially therapeutic option but has been complicated by reports of infection. Surgical excision remains the standard of care allowing for symptomatic resolution and definitive diagnosis via pathologic examination; minimally invasive approaches such as robotic and thoracoscopic approaches aiding treatment. Following complete resection, prognosis is excellent with essentially no recurrence. Methods: A review of the available electronic literature was performed from 1975 through 2022, using PubMed and Google Scholar, with an emphasis on more recent series. We included all retrospective series and case reports. A single author identified the studies, and all authors reviewed the selection until there was a consensus on which studies to include. Key Content and Findings: The literature consisted of relatively small series, mixed between adult and pediatric patients, and the consensus remains that all symptomatic lesions should be excised via minimally invasive approach where feasible. Conclusions: Surgical excision of symptomatic bronchogenic cysts remains the gold standard, with endoscopic drainage being reserved for diagnosis or as a temporizing measure in clinically unstable patients.

Computed tomography reveals hypertrophic remodelling of the diaphragm in cystic fibrosis but not in COPD.

Background: Computed tomography (CT) is increasingly used for assessing skeletal muscle characteristics. In cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), reduced limb muscle mass predicts poor clinical outcomes. However, the degree to which quantity or quality of respiratory and nonrespiratory muscles is affected by these diseases remains controversial. Methods: Thoracic CT images of 29 CF, 21 COPD and 20 normal spirometry control subjects were analysed to measure indices of muscle quantity (volume or cross-sectional area) and quality (radiodensity) in respiratory (diaphragm, abdominal) and nonrespiratory (pectoralis, lumbar paraspinal) muscles. Multivariable linear regression assessed relationships of CT measurements with body mass index (BMI), forced expiratory volume in 1 s (FEV1) % pred, inflammation and infection biomarkers, nutritional status and CF genotype. Results: Diaphragm volume in CF was significantly higher than in COPD (by 154%) or controls (by 140%). Abdominal muscle area in CF was also greater than in COPD (by 130%). Nonrespiratory muscles in COPD had more low radiodensity muscle (marker of lipid content) compared to CF and controls. In CF but not COPD, higher BMI and FEV1 % pred were independently associated with higher diaphragm and/or abdominal muscle quantity indices. Serum creatinine also predicted respiratory and nonrespiratory muscle quantity in CF, whereas other biomarkers including genotype correlated poorly with muscle CT parameters. Conclusions: Our data suggest that the CF diaphragm undergoes hypertrophic remodelling, whereas in COPD the nonrespiratory muscles show altered muscle quality consistent with greater lipid content. Thoracic CT can thus identify distinctive respiratory and nonrespiratory muscle remodelling signatures associated with different chronic lung diseases.

Cerebral venous sinus thrombosis related to SARS-CoV-2 infection in a pediatric patient: A case report.

Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); it has recently been associated with several hematologic disorders. A 4-year-old boy who had SARS-CoV-2 10 months prior was admitted to the emergency department of our hospital with seizures. His SARS-CoV-2 IgG II level was 885.7 AU/mL. Neuroimaging with cranial computed tomography after admission showed abnormal images of the venous sinus, but this was not sufficient to diagnose cerebral venous sinus thrombosis. Therefore, magnetic resonance imaging and digital subtraction angiography were conducted, which confirmed the diagnosis. He was treated with thrombectomy and anticoagulation drugs, and the clinical outcomes were satisfactory. Because our patient had a medical history of SARS-CoV-2 and exhibited no other risk factors, we present this case as evidence of a potential association between cerebral venous sinus thrombosis and SARS-CoV-2.

Developmental models of motor-evoked potential features by transcranial magnetic stimulation across age groups from childhood to adulthood.

To derive the maturation of neurophysiological processes from childhood to adulthood reflected by the change of motor-evoked potential (MEP) features. 38 participants were recruited from four groups (age mean in years [SD in months], number (males)): children (7.3 [4.2], 7(4)), preadolescents (10.3 [6.9], 10(5)), adolescents (15.3 [9.8], 11(5)), and adults (26.9 [46.2], 10(5)). The navigated transcranial magnetic stimulation was performed on both hemispheres at seven stimulation intensity (SI) levels from sub- to supra-threshold and targeted to the representative cortical area of abductor pollicis brevis muscle. MEPs were measured from three hand- and two forearm-muscles. The input-output (I/O) curves of MEP features across age groups were constructed using linear mixed-effect models. Age and SI significantly affected MEP features, whereas the stimulated side had a minor impact. MEP size and duration increased from childhood to adulthood. MEP onset- and peak-latency dropped in adolescence, particularly in hand muscles. Children had the smallest MEPs with the highest polyphasia, whereas I/O curves were similar among preadolescents, adolescents, and adults. This study illustrates some of the changing patterns of MEP features across the ages, suggesting developing patterns of neurophysiological processes activated by TMS, and to motivate studies with larger sample size.

Nanoplasmonic amplification in microfluidics enables accelerated colorimetric quantification of nucleic acid biomarkers from pathogens.

Deployment of nucleic acid amplification assays for diagnosing pathogens in point-of-care settings is a challenge due to lengthy preparatory steps. We present a molecular diagnostic platform that integrates a fabless plasmonic nano-surface into an autonomous microfluidic cartridge. The plasmonic 'hot' electron injection in confined space yields a ninefold kinetic acceleration of RNA/DNA amplification at single nucleotide resolution by one-step isothermal loop-mediated and rolling circle amplification reactions. Sequential flow actuation with nanoplasmonic accelerated microfluidic colorimetry and in conjugation with machine learning-assisted analysis (using our 'QolorEX' device) offers an automated diagnostic platform for multiplexed amplification. The versatility of QolorEX is demonstrated by detecting respiratory viruses: SARS-CoV-2 and its variants at the single nucleotide polymorphism level, H1N1 influenza A, and bacteria. For COVID-19 saliva samples, with an accuracy of 95% on par with quantitative polymerase chain reaction and a sample-to-answer time of 13 minutes, QolorEX is expected to advance the monitoring and rapid diagnosis of pathogens.

Successful thrombectomy of top-of-the-basilar artery occlusion - difficult to detect in clinical practice: A case report.

Top-of-the-basilar artery occlusion frequently causes infarction of the midbrain, thalamus, and portions of the temporal and occipital lobes as the vascular supply of these regions comes from the posterior communicating and posterior cerebral arterial tributaries of the basilar artery. Clinical signs include an array of visual, oculomotor, and behavioral abnormalities, usually without prominent motor dysfunction, which makes diagnosis challenging for those inexperienced with these sign. We describe a 59-year-old male presenting with acute ischemic stroke due to top-of-the-basilar artery occlusion. Despite attempting several paraclinical examinations relating the sudden coma with Glasgow Coma Scale of 6 points, the neuroimaging detected the large vessel occlusion that was difficult to recognize. After confirming top-of-the-basilar artery occlusion, the recanalization was realized immediately. The patient was discharged with good clinical recovery.

Low-Grade Inflammation in Gestational Diabetes Mellitus and Its Correlation with Maternal Insulin Resistance and Fetal Growth Indices.

Introduction: Chronic low-grade inflammation (LGI) plays a role in the pathogenesis of gestational diabetes mellitus (GDM). LGI, on the one hand, promotes insulin resistance and at the same time, affects fetal development. The study aimed to use clinically feasible means to evaluate the association between maternal LGI and maternal insulin resistance and fetal growth indices by ultrasound in the third trimester. Methods: A crossectional and descriptive study on 248 first-time diagnosed GDM in Vietnam. Results: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) indices were significantly higher in GDM than in normal glucose-tolerant pregnancies (p = 0.048 and 0.016, respectively). GDM with LGI witnessed significantly higher systolic blood pressure, BMI, HbA1c, and significantly lower quantitative Insulin Sensitivity Check Index (QUICKI) than those without LGI. After adjusting for maternal BMI, fasting plasma glucose (FPG), age, and parity, C-reactive protein (CRP) was positively correlated with HOMA2-IR (B=0.13, p<0.01) and Mathews index (B=0.29, p<0.01). Regarding fetal characteristics, LGI was associated with fetal growth indices in the third trimester of GDM. NLR was negatively correlated with estimated fetal weight (EFW) (B=-64.4, p<0.05) after adjusting for maternal BMI and FPG. After adjusting for maternal BMI, FPG, age, and parity, PLR was negatively correlated with biparietal diameter (B=-0.02, p<0.01) and abdominal circumference (AC) (B=-0.16, p<0.05), and EFW (B=-1.1, p<0.01), and head circumference (HC) (B=-0.06, p<0.01); CRP was negatively correlated with AC (B=-0.16, p<0.001), EFW (B=-85.3, p<0.001), and HC (B=-5.0, p<0.001). Conclusion: In the third trimester, LGI was associated with maternal glucose and insulin resistance in GDM. Moreover, LGI was associated with fetal characteristics in ultrasonic images. There were negative correlations between LGI and fetal developmental characteristics.

Single nucleotide variants in Pseudomonas aeruginosa populations from sputum correlate with baseline lung function and predict disease progression in individuals with cystic fibrosis.

The severity and progression of lung disease are highly variable across individuals with cystic fibrosis (CF) and are imperfectly predicted by mutations in the human gene CFTR, lung microbiome variation or other clinical factors. The opportunistic pathogen Pseudomonas aeruginosa (Pa) dominates airway infections in most CF adults. Here we hypothesized that within-host genetic variation of Pa populations would be associated with lung disease severity. To quantify Pa genetic variation within CF sputum samples, we used deep amplicon sequencing (AmpliSeq) of 209 Pa genes previously associated with pathogenesis or adaptation to the CF lung. We trained machine learning models using Pa single nucleotide variants (SNVs), microbiome diversity data and clinical factors to classify lung disease severity at the time of sputum sampling, and to predict lung function decline after 5 years in a cohort of 54 adult CF patients with chronic Pa infection. Models using Pa SNVs alone classified lung disease severity with good sensitivity and specificity (area under the receiver operating characteristic curve: AUROC=0.87). Models were less predictive of lung function decline after 5 years (AUROC=0.74) but still significantly better than random. The addition of clinical data, but not sputum microbiome diversity data, yielded only modest improvements in classifying baseline lung function (AUROC=0.92) and predicting lung function decline (AUROC=0.79), suggesting that Pa AmpliSeq data account for most of the predictive value. Our work provides a proof of principle that Pa genetic variation in sputum tracks lung disease severity, moderately predicts lung function decline and could serve as a disease biomarker among CF patients with chronic Pa infections.

Reliability and validity of the Vietnamese version of the Hamilton D-17 scale.

Background: While depression is a common mental disorder, the diagnosis of this condition is still challenging. Thus, there is a need to have a validated tool to help evaluate symptoms of depression. This study aimed to evaluate the reliability and validity of the Vietnamese version of the Hamilton D-17 scale. Methods: A cross-sectional, descriptive, and validation study was conducted on 183 patients including 139 depressed and 44 non-depressed patients at the University Medical Center of Medicine and Pharmacy University at Ho Chi Minh City. Internal reliability and inter-rater reliability was measured using Cronbach's alpha and intraclass correlation coefficients (ICC). Confirmatory factor analysis (CFA) was used to evaluate construct validity. The Patient Health Questionnaire (PHQ9) was used to measure concurrent validity of the Hamilton D-17. Area under the ROC curve was used to measure criterion validity. Results: Both Cronbach alpha coefficient and ICC were at good level at alpha = 0.83 and ICC = 0.83. CFA with a second-order model consisting of four factors fitted the data at good to excellent level. The SRMR (Standardized Root Mean Squared Residual) was 0.066, RMSEA (Root Mean Square Error of Approximation) (90% CI) was 0.053 (0.036-0.069), CFI (comparative fit index) was 0.93, TLI (Tucker Lewis index) was 0.92. The Hamilton D-17 and the PHQ-9 had a correlation coefficient of r = 0.77 (p < 0.001). The Hamilton D-17 had a very high level of criterion validity with AUC of 0.93 (0.88-0.98). Conclusion: The Vietnamese version of the Hamilton D-17 scale has a high level of validity and reliability. The scale should be used to assess symptoms of depression among Vietnamese patients.

Disparities in Survival Due to Social Determinants of Health and Access to Treatment in US Patients With Operable Malignant Pleural Mesothelioma.

Importance: Outcomes of localized malignant pleural mesothelioma (MPM) remain poor despite multimodality therapy. It is unclear what role disparities have in the overall survival (OS) of patients with operable MPM. Objective: To examine survival disparities associated with social determinants of health (SDOHs) and treatment access in patients with malignant pleural mesothelioma. Design, Setting, and Participants: In this observational, retrospective cohort study, patients with MPM diagnosed between January 1, 2004, and December 31, 2017, were identified from the National Cancer Database with a maximum follow-up time of 13.6 years. The analysis was conducted from February 16, 2022, to July 29, 2022. Patients were included if they were diagnosed with potentially resectable clinical stage I to IIIA MPM, had epithelioid and biphasic histologic subtypes, and received chemotherapy. Patients were excluded if they could not receive curative surgery, were 75 years or older, or had metastasis, unknown stage, or tumor extension to the chest wall, mediastinal tissues, or organs. Exposures: Chemotherapy alone vs chemotherapy with curative surgery in the form of pleurectomy and decortication or extrapleural pneumonectomy. Main Outcomes and Measures: The primary end point was OS. Cox proportional hazards regression models were used to determine hazard ratios (HRs) for OS, including univariable and multivariable models controlling for potential confounders, including demographic, comorbidity, clinical, treatment, tumor, and hospital-related variables, as well as SDOHs. Results: A total of 1389 patients with MPM were identified (median [IQR] age, 66 [61-70] years; 1024 [74%] male; 12 [1%] Asian, 49 [3%] Black, 74 [5%] Hispanic, 1233 [89%] White, and 21 [2%] of other race). The median OS was 1.7 years (95% CI, 1.6-1.8). Risk factors associated with worse OS included older age, male sex, Black race, low income, and low educational attainment. Factors associated with greater odds of survival included receipt of surgical therapy, recent year of treatment, increased distance to travel, and treatment at high-volume academic hospitals. The risk factors most strongly associated with poor OS included Black race (HR, 1.96; 95% CI, 1.43-2.69) and male sex (HR, 1.60; 95% CI, 1.38-1.86). Surgical treatment in addition to systemic chemotherapy (HR, 0.70; 95% CI, 0.61-0.81) was independently associated with improved OS, as were chemotherapy initiation (HR, 0.93; 95% CI, 0.87-0.99) and greater travel distance from the hospital (HR, 0.92; 95% CI, 0.86-0.98). Conclusions and Relevance: In this retrospective cohort study of patients with operable MPM, there was significant variability in access to care by SDOHs. Addressing disparities in access to multimodality therapy can help ensure equity of care for patients with MPM.

Discovery of cyanophycin dipeptide hydrolase enzymes suggests widespread utility of the natural biopolymer cyanophycin.

Cyanophycin is a bacterial polymer mainly used for nitrogen storage. It is composed of a peptide backbone of L-aspartate residues with L-arginines attached to their side chains through isopeptide bonds. Cyanophycin is degraded in two steps: Cyanophycinase cleaves the polymer into ß-Asp-Arg dipeptides, which are hydrolyzed into free Asp and Arg by enzymes possessing isoaspartyl dipeptide hydrolase activity. Two unrelated enzymes with this activity, isoaspartyl dipeptidase (IadA) and isoaspartyl aminopeptidase (IaaA) have been shown to degrade ß-Asp-Arg dipeptides, but bacteria which encode cyanophycin-metabolizing genes can lack iaaA and iadA genes. In this study, we investigate a previously uncharacterized enzyme whose gene can cluster with cyanophycin-metabolizing genes. This enzyme, which we name cyanophycin dipeptide hydrolase (CphZ), is specific for dipeptides derived from cyanophycin degradation. Accordingly, a co-complex structure of CphZ and ß-Asp-Arg shows that CphZ, unlike IadA or IaaA, recognizes all portions of its ß-Asp-Arg substrate. Bioinformatic analyses showed that CphZ is found in very many proteobacteria and is homologous to an uncharacterized protein encoded in the "arginine/ornithine transport" (aot) operon of many pseudomonas species, including Pseudomonas aeruginosa. In vitro assays show that AotO is indeed a CphZ, and in cellulo growth experiments show that this enzyme and the aot operon allow P. aeruginosa to take up and use ß-Asp-Arg as a sole carbon and nitrogen source. Together the results establish the novel, highly specific enzyme subfamily of CphZs, suggesting that cyanophycin is potentially used by a much wider range of bacteria than previously appreciated.

Identification of biomarkers to stratify response to B-cell-targeted therapies in systemic lupus erythematosus: an exploratory analysis of a randomised controlled trial.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with widespread immune dysregulation and diverse clinical features. Immune abnormalities might be differentially associated with specific organ involvement or response to targeted therapies. We aimed to identify biomarkers of response to belimumab after rituximab to facilitate a personalised approach to therapy. Methods: In this exploratory analysis of a randomised controlled trial (BEAT-LUPUS), we investigated immune profiles of patients with SLE recruited to the 52-week clinical trial, which tested the combination of rituximab plus belimumab versus rituximab plus placebo. We used machine learning and conventional statistics to investigate relevant laboratory and clinical biomarkers associated with major clinical response. BEAT LUPUS is registered at ISRCTN, 47873003, and is now complete. Findings: Between Feb 2, 2017, and March 28, 2019, 52 patients were recruited to BEAT-LUPUS, of whom 44 provided clinical data at week 52 and were included in this analysis. 21 (48%) of 44 participants were in the belimumab group (mean age 39·5 years [SD 12·1]; 17 [81%] were female, four [19%] were male, 13 [62%] were White) and 23 (52%) were in the placebo group (mean age 42·1 years [SD 10·5]; 21 [91%] were female, two [9%] were male, 16 [70%] were White). Ten (48%) of 21 participants who received belimumab after rituximab and eight (35%) of 23 who received placebo after rituximab had a major clinical response at 52 weeks (between-group difference of 13% [95% CI -15 to 38]). We found a predictive association between baseline serum IgA2 anti-double stranded DNA (dsDNA) antibody concentrations and clinical response to belimumab after rituximab, with a between-group difference in major clinical response of 48% (95% CI 10 to 70) in patients with elevated baseline serum IgA2 anti-dsDNA antibody concentrations. Moreover, among those who had a major clinical response, serum IgA2 anti-dsDNA antibody concentrations significantly decreased from baseline only in the belimumab group. Increased circulating IgA2 (but not total) plasmablast numbers, and T follicular helper cell numbers predicted clinical response and were both reduced only in patients who responded to belimumab after rituximab. Serum IgA2 anti-dsDNA antibody concentrations were also associated with active renal disease, whereas serum IgA1 anti-dsDNA antibody and IFN-α concentrations were associated with mucocutaneous disease activity but did not predict response to B-cell targeted therapy. Patients with a high baseline serum interleukin-6 concentration were less likely to have a major clinical response, irrespective of therapy. Interpretation: This exploratory study revealed the presence of distinct molecular networks associated with renal and mucocutaneous involvement, and response to B-cell-targeted therapies, which, if confirmed, could guide precision targeting of advanced therapies for this heterogenous disease. Funding: Versus Arthritis, UCLH Biomedical Research Centre, LUPUS UK, and GSK.