Regulation of mitochondrial protein import by cytosolic kinases.

Mitochondria import a large number of nuclear-encoded proteins via membrane-bound transport machineries; however, little is known about regulation of the preprotein translocases. We report that the main protein entry gate of mitochondria, the translocase of the outer membrane (TOM complex), is phosphorylated by cytosolic kinases-in particular, casein kinase 2 (CK2) and protein kinase A (PKA). CK2 promotes biogenesis of the TOM complex by phosphorylation of two key components, the receptor Tom22 and the import protein Mim1, which in turn are required for import of further Tom proteins. Inactivation of CK2 decreases the levels of the TOM complex and thus mitochondrial protein import. PKA phosphorylates Tom70 under nonrespiring conditions, thereby inhibiting its receptor activity and the import of mitochondrial metabolite carriers. We conclude that cytosolic kinases exert stimulatory and inhibitory effects on biogenesis and function of the TOM complex and thus regulate protein import into mitochondria.

Multiple Barriers Impede Screening for Hepatitis Delta: An Internet-Based Survey of Healthcare Providers.

INTRODUCTION: Hepatitis delta virus (HDV) increases risk of cirrhosis and hepatocellular carcinoma in patients with hepatitis B; however, HDV screening rates are low. We assessed providers' perceived barriers to HDV screening and management. METHODS: We distributed an Internet-based survey to members of 3 gastroenterology/hepatology organizations. RESULTS: Most respondents, 69.3%, correctly identified the appropriate HDV screening test. Several reported barriers to HDV care, including uncertainty of screening criteria, 55.5%, and lack of treatment knowledge, 66.7%. DISCUSSION: Our findings highlight the need for increased education regarding HDV care. Education should be combined with standardized approaches that increase ease of HDV screening.

Marijuana Use in Middle and High School Students: Insights from the 2020 National Youth Tobacco Survey.

OBJECTIVE: The use of marijuana by middle and high school students could have important consequences, including physical harm, poor decision making, increased use of tobacco products, and involvement in the legal system. Determining the level of use by students provides the initial information needed to understand the extent of the problem and possible approaches to reducing student use. METHODS: The National Youth Tobacco Surveys provide important information about the frequency of use of nicotine and tobacco products by a representative sample of students in schools in the United States. The 2020 survey included a question about the use of marijuana by survey respondents. The results from the survey were analyzed using descriptive statistics and logistic regression to model the association between the use of marijuana and the use of electronic or conventional cigarettes. RESULTS: The final survey from 2020 included 13,357 students, with 6537 male respondents and 6820 female respondents. Ages ranged from younger than 12 to 18 and older years; 961 students used both cigarettes and marijuana, and 1880 students used both electronic cigarettes (e-cigarettes) and marijuana. The adjusted odds ratio for the use of marijuana increased in female students, in non-Hispanic Black students, Hispanic students, and all ages from 13 through 18 and older. The perception of harm associated with either e-cigarettes or cigarettes did not change the odds ratio for using marijuana. Students who did not smoke cigarettes or did not smoke e-cigarettes had significantly lower odds ratios for using marijuana. CONCLUSIONS: The 2020 National Youth Tobacco Survey indicates that approximately 18.4% of middle school and high school students have used marijuana. Parents, educators, public health officials, and policymakers need to understand that there is a relatively high use of marijuana among students and that education programs should focus on its use with or without other tobacco products.

Feasibility and Acceptability of an Abbreviated, Four-Week Mindfulness Program for Chronic Pain Management.

OBJECTIVE: The Mindfulness-Based Stress Reduction program is effective at improving chronic pain outcomes, but the time demand hinders participation. This preliminary study evaluated the feasibility, acceptability, and potential effects of providing an abbreviated mindfulness program for patients with chronic pain. DESIGN: A single-arm, mixed-methods, pre-post intervention study. SETTING: An outpatient rehabilitation clinic at an academic medical center. SUBJECTS: Participants were N = 23 adults with chronic pain who were new to mindfulness practice. METHODS: Mindfulness-based Stress Reduction was adapted to shorten the program to four weekly 90-minute sessions and to focus content on pain management. Three cohorts of six to nine participants completed baseline and post-treatment measures of 1) patient-reported outcomes, including pain intensity, pain interference, physical functioning, depressive/anxiety symptoms, positive affect and well-being, and sleep disturbance; 2) pain medication dosages; 3) psychosocial variables including pain acceptance, pain catastrophizing, and perceived stress; 4) dispositional mindfulness, as well as postintervention structured interviews about their experiences. RESULTS: Acceptable rates of retention and attendance and high ratings of satisfaction indicated that the intervention was feasible and acceptable. In interviews, participants found the program acceptable and beneficial and provided suggestions to improve it. From pre- to post-treatment, significant improvements were reported in all measures except physical functioning and anxiety. CONCLUSIONS: In adults with chronic pain, a four-week mindfulness program is feasible and acceptable, addresses the barrier of a lengthy program, and may improve quality of life and psychological functioning. An appropriately powered randomized controlled trial with a comparison group is needed to assess the intervention's effectiveness.

Use of Premixed Insulin, Metformin, and a Glucagon-Like Peptide 1 Receptor Agonist as a Therapeutic Approach for Uncontrolled Type 2 Diabetes.

OBJECTIVE | To explore the use of premixed insulin, a glucagon-like peptide 1 (GLP-1) receptor agonist, and metformin as combination therapy for type 2 diabetes. DESIGN AND METHODS | All adult patients with type 2 diabetes who had been prescribed premixed insulin and a GLP-1 receptor agonist simultaneously at our outpatient clinic were selected for retrospective review. We reviewed A1C, weight, cumulative daily insulin dose, and adverse events over 12 months. RESULTS | A total of 72 patients received premixed insulin and a GLP-1 receptor agonist, of which 32 met inclusion criteria. The average duration of type 2 diabetes for these patients was 14.2 ± 7.1 years. Mean A1C at baseline was 10.5 ± 2.1%. At 12 months, mean A1C was 8.3 ± 1.9%. The change in mean A1C after 12 months was -2.2% (95% CI -3.433 to -1.014, P <0.0001). At 12 months, the mean cumulative insulin dose was 33.3 units less than before the therapy change (95% CI -57.13 to -9.46, P = 0.0030). Average weight change at 12 months was -2.2 kg (95% CI -27.6 to 37.6, P = NS). After 12 months, 61% of included patients (19 of 31) had an A1C ≤8%. Six additional patients were not included in analysis because they stopped the regimen after <3 months because of adverse events. CONCLUSION | Despite a decreased cumulative daily dose of insulin, patients with historically uncontrolled type 2 diabetes using metformin, premixed insulin, and a GLP-1 receptor agonist in combination experienced improved glycemic control over 12 months. Prospective randomized trials are needed to better assess the potential benefit of this combination therapy.

CK1δ and CK1ε are components of human 40S subunit precursors required for cytoplasmic 40S maturation.

Biogenesis of 40S pre-ribosomal subunits requires many trans-acting factors, among them several protein kinases. In this study, we show that the human casein kinase 1 (CK1) isoforms δ and ε are required for cytoplasmic maturation steps of 40S subunit precursors. We show that both CK1δ and CK1ε isoforms are components of pre-40S subunits, on which they phosphorylate the ribosome biogenesis factors ENP1/BYSL and LTV1. Inhibition or co-depletion of CK1δ and CK1ε results in failure to recycle a series of trans-acting factors including ENP1/BYSL, LTV1, RRP12, DIM2/PNO1, RIO2 and NOB1 from pre-40S particles after nuclear export. Furthermore, co-depletion of CK1δ and CK1ε leads to defects in 18S-E pre-rRNA processing. Together, these data demonstrate that CK1δ and CK1ε play a decisive role in triggering late steps of pre-40S maturation that are required for acquisition of functionality of 40S ribosomal subunits in protein translation.

Intermembrane space proteome of yeast mitochondria.

The intermembrane space (IMS) represents the smallest subcompartment of mitochondria. Nevertheless, it plays important roles in the transport and modification of proteins, lipids, and metal ions and in the regulation and assembly of the respiratory chain complexes. Moreover, it is involved in many redox processes and coordinates key steps in programmed cell death. A comprehensive profiling of IMS proteins has not been performed so far. We have established a method that uses the proapoptotic protein Bax to release IMS proteins from isolated mitochondria, and we profiled the protein composition of this compartment. Using stable isotope-labeled mitochondria from Saccharomyces cerevisiae, we were able to measure specific Bax-dependent protein release and distinguish between quantitatively released IMS proteins and the background efflux of matrix proteins. From the known 31 soluble IMS proteins, 29 proteins were reproducibly identified, corresponding to a coverage of >90%. In addition, we found 20 novel intermembrane space proteins, out of which 10 had not been localized to mitochondria before. Many of these novel IMS proteins have unknown functions or have been reported to play a role in redox regulation. We confirmed IMS localization for 15 proteins using in organello import, protease accessibility upon osmotic swelling, and Bax-release assays. Moreover, we identified two novel mitochondrial proteins, Ymr244c-a (Coa6) and Ybl107c (Mic23), as substrates of the MIA import pathway that have unusual cysteine motifs and found the protein phosphatase Ptc5 to be a novel substrate of the inner membrane protease (IMP). For Coa6 we discovered a role as a novel assembly factor of the cytochrome c oxidase complex. We present here the first and comprehensive proteome of IMS proteins of yeast mitochondria with 51 proteins in total. The IMS proteome will serve as a valuable source for further studies on the role of the IMS in cell life and death.

Characterization of a lipid-based jumbo phage compartment as a hub for early phage infection.

Viral genomes are most vulnerable to cellular defenses at the start of the infection. A family of jumbo phages related to phage ΦKZ, which infects Pseudomonas aeruginosa, assembles a protein-based phage nucleus to protect replicating phage DNA, but how it is protected prior to phage nucleus assembly is unclear. We find that host proteins related to membrane and lipid biology interact with injected phage protein, clustering in an early phage infection (EPI) vesicle. The injected virion RNA polymerase (vRNAP) executes early gene expression until phage genome separation from the vRNAP and the EPI vesicle, moving into the nascent proteinaceous phage nucleus. Enzymes involved in DNA replication and CRISPR/restriction immune nucleases are excluded by the EPI vesicle. We propose that the EPI vesicle is rapidly constructed with injected phage proteins, phage DNA, host lipids, and host membrane proteins to enable genome protection, early transcription, localized translation, and to ensure faithful genome transfer to the proteinaceous nucleus.

Cardiac Muscle Injury and Echocardiographic Plus Electrocardiographic Findings in Patients With 2019 Novel Coronavirus (COVID-19): A Retrospective Cohort Study.

Background: Myocardial injury has been described in coronavirus-2019 (COVID-19). Few studies have reported cardiovascular imaging data with transthoracic echocardiography (TTE) and electrocardiography (ECG) findings in COVID-19 patients, and their correlation with mortality. Methods: We conducted a retrospective cohort study that included COVID-19 patients from March 2020 through February 2021 who had TTE and ECG during hospital admission. Myocardial injury was defined by an elevated high-sensitivity troponin T level > 20 ng/L. Bivariate analysis was used to compare patients with myocardial injury and those without. Multivariate logistic regression analysis was performed to identify the variables associated with mortality. Results: A total of 438 patients were included. The mean age was 62.1 ± 14.9 years, and 58.9% were male. A total of 149 patients died, with a mortality rate of 34%. A total of 260 patients (59.4%) had myocardial injury. The average left ventricular ejection fraction was 59.8% ± 11.2%, with 30 patients (6.8%) having an ejection fraction of < 40%. Patients with myocardial injury had higher mortality than those without (P < 0.05, χ2 test). A multiple regression analysis model indicated that age, race and/or ethnicity, the development of acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the variables significantly associated with mortality. Conclusion: COVID-19 patients with myocardial injury had higher mortality than those without. Age, race and/or ethnicity, acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the clinical variables associated with mortality. The TEE and ECG variables studied were not significantly associated with mortality.

Contexte: Des atteintes myocardiques ont été décrites en présence d'une infection par le coronavirus 2019 (COVID-19). Quelques études ont rapporté des données d'imagerie cardiovasculaire obtenues par échocardiographie transthoracique (ETT) et électrocardiographie (ECG) chez des patients atteints de la COVID-19, et leur corrélation avec la mortalité. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant des patients atteints de la COVID-19 entre mars 2020 et février 2021 qui ont été soumis à une ETT ou à une ECG pendant leur hospitalisation. L'atteinte myocardique était définie comme un taux élevé de troponine T de haute sensibilité > 20 ng/L. Une analyse à deux variables a été utilisée pour comparer les patients présentant une atteinte myocardique et ceux qui n'en présentaient pas. Une analyse de régression logistique à multiples variables a été menée pour définir les variables qui étaient associées à la mortalité. Résultats: L'étude comptait un total de 438 patients. L'âge moyen était de 62,1 ± 14,9 ans; 58,9 % étaient des hommes. Un total de 149 patients sont décédés, soit un taux de mortalité de 34 %. Un total de 260 patients (59,4 %) présentaient une atteinte myocardique. La fraction d'éjection ventriculaire gauche moyenne était de 59,8 % ± 11,2 %, alors que 30 patients (6,8 %) affichaient une fraction d'éjection inférieure à 40 %. Le taux de mortalité était plus élevé chez les patients qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas (p < 0,05, test χ2). Selon un modèle d'analyse de régression multiple, l'âge, la race et/ou l'ethnicité, l'apparition du syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables fortement liées à la mortalité. Conclusion: Parmi les patients atteints de la COVID-19, la mortalité était plus élevée chez ceux qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas. L'âge, la race et/ou l'ethnicité, le syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables cliniques liées à la mortalité. Les variables d'ETT et d'ECG étudiées n'avaient pas de lien important avec la mortalité.

The Influenza-Induced Pulmonary Inflammatory Exudate in Susceptible Tpl2-Deficient Mice Is Dictated by Type I IFN Signaling.

The most prominent host response to viral infection is the production of type 1 interferons (T1 IFNs). One host regulator of the T1 IFNs is the serine-threonine kinase, tumor progression locus 2 (TPL2). We have previously demonstrated that Tpl2-/- mice succumb to infection with a low-pathogenicity influenza A strain (x31), in association with with increased pulmonary levels of interferon-ß (IFN-ß), chemokine CCL2, and excessive monocyte and neutrophil pulmonary infiltration. TPL2-dependent overexpression of IFN-ß has been implicated in enhanced susceptibility to Mycobacterium tuberculosis; therefore, we examined the role of T1 IFNs in susceptibility of Tpl2-/- mice to influenza. CCL2 overexpression and monocyte recruitment were normalized in Ifnar1-/-Tpl2-/- mice, confirming that TPL2 constrains inflammatory monocyte recruitment via inhibition of the T1 IFN/CCL2 axis. Unexpectedly, excessive neutrophil recruitment in Ifnar1-/- strains was further exacerbated by simultaneous TPL2 genetic ablation in Ifnar1-/-Tpl2-/- by 7 dpi, accompanied by overexpression of neutrophil-regulating cytokines, CXCL1 and IFN-λ. Collectively, our data suggest that TPL2 and T1 IFNs synergize to inhibit neutrophil recruitment. However, treatment with the neutrophil-depleting anti-Ly6G antibody showed only a modest improvement in disease. Analysis of sorted innate immune populations revealed redundant expression of inflammatory mediators among neutrophils, inflammatory monocytes and alveolar macrophages. These findings suggest that targeting a single cell type or mediator may be inadequate to control severe disease characterized by a mixed inflammatory exudate. Future studies will consider TPL2-regulated pathways as potential predictors of severe influenza progression as well as investigate novel methods to modulate TPL2 function during viral infection.

An Analysis of Nicotine Pouch Use by Middle School and High School Students Surveyed by the National Youth Tobacco Survey in 2021 and a Review of the Literature.

OBJECTIVES: The use of alternative nicotine products by middle and high school students is a growing concern due to industry marketing techniques, availability, and popularity of new products, and ambiguous nicotine concentrations. The 2021 National Youth Tobacco Survey (NYTS) provides information about the frequency, and characteristics of middle, and high school students who have used nicotine pouches. METHODS: The National Youth Tobacco Surveys provide important information about the frequency of use of tobacco and alternative nicotine products by a representative sample of students in schools in the United States. The 2021 survey included questions about the use of nicotine pouches/dissolvable tobacco products. The results from the survey were analysis using descriptive statistics, and logistic regression to model the association between the use of these alternative nicotine products, and the use of electronic cigarettes or the use of conventional cigarettes. RESULTS: A total of 20 413 students participated in the survey year 2021; 17 842 were included in the final data analysis. Their ages ranged from 9 to 18+. Identified risk factors for the use of alternative nicotine products included race, and age. The adjusted odds ratio (OR) was lower in non-Hispanic Black and Hispanic students, as compared to non-Hispanic White students. Older students had a substantially higher risk of using nicotine/dissolvable tobacco products, specifically, compared to students less than or equal to 13 years old. The OR increased 174% (OR: 2.74; 1.70-4.41) in 17-year-old students. The perception of harm associated with electronic cigarettes increased the likelihood of using alternative nicotine products. Students who did not smoke cigarettes (OR: 0.39; 0.27-0.56) or did not smoke electronic cigarettes (OR: 0.20; 0.18-0.40) had significantly lower OR for using alternative nicotine products. CONCLUSIONS: The 2021 National Youth Tobacco Survey indicates that a relatively small percentage of middle school and high school student have used nicotine pouches. However, with the increase in new, alternative tobacco products, understanding adolescent use in comparison to other tobacco products is an important trend to monitor.

Self-compassion training to improve well-being for surgical residents.

CONTEXT: Burnout remains prevalent among surgical residents. Self-compassion training may serve to improve their well-being. OBJECTIVE: To evaluate the impact on well-being of a self-compassion program modified for surgical residents. DESIGN: This is a 3-year, mixed-methods study using pre-post surveys and focus groups to identify areas for programmatic improvement and the subsequent impact of the modifications. SETTING: A single academic institution. PARTICIPANTS: Surgical residents participating in a self-compassion program. INTERVENTIONS: A self-compassion program adapted from a larger course to fit the needs of surgical residents. MAIN OUTCOME MEASURES: Themes relating to the program's strengths and weaknesses were identified through participant focus groups. Well-being was assessed through validated measurement tools, including The Maslach Burnout Inventory (MBI), Patient Health Questionnaire-9, Perceived Stress Scale, and Spielberger State-Trait Anxiety Inventory-6. RESULTS: 95 residents participated in the self-compassion program, of which 40 residents completed both surveys (total response rate: 42%). All participants demonstrated severe burnout pre-program, based on scores of at least one of the MBI subscales. Emotional exhaustion scores improved post-program, with larger improvements seen after program modifications (2018: 58% vs 2020: 71%). Focus group findings demonstrated that residents need a safe and distraction-free space to practice self-compassion, and program engagement improved following modifications.

RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing.

The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5´-GNGG-3´ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contribute to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the Bact spliceosomal complex. Thus, our findings suggest an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation.

Tumor Progression Locus 2 Protects against Acute Respiratory Distress Syndrome in Influenza A Virus-Infected Mice.

Excessive inflammation in patients with severe influenza disease may lead to acute lung injury that results in acute respiratory distress syndrome (ARDS). ARDS is associated with alveolar damage and pulmonary edema that severely impair gas exchange, leading to hypoxia. With no existing FDA-approved treatment for ARDS, it is important to understand the factors that lead to virus-induced ARDS development to improve prevention, diagnosis, and treatment. We have previously shown that mice deficient in the serine-threonine mitogen-activated protein kinase, Tpl2 (MAP3K8 or COT), succumb to infection with a typically low-pathogenicity strain of influenza A virus (IAV; HKX31, H3N2 [x31]). The goal of the current study was to evaluate influenza A virus-infected Tpl2-/- mice clinically and histopathologically to gain insight into the disease mechanism. We hypothesized that Tpl2-/- mice succumb to IAV infection due to development of ARDS-like disease and pulmonary dysfunction. We observed prominent signs of alveolar septal necrosis, hyaline membranes, pleuritis, edema, and higher lactate dehydrogenase (LDH) levels in the lungs of IAV-infected Tpl2-/- mice compared to wild-type (WT) mice from 7 to 9 days postinfection (dpi). Notably, WT mice showed signs of regenerating epithelium, indicative of repair and recovery, that were reduced in Tpl2-/- mice. Furthermore, biomarkers associated with human ARDS cases were upregulated in Tpl2-/- mice at 7 dpi, demonstrating an ARDS-like phenotype in Tpl2-/- mice in response to IAV infection. IMPORTANCE This study demonstrates the protective role of the serine-threonine mitogen-activated protein kinase, Tpl2, in influenza virus pathogenesis and reveals that host Tpl2 deficiency is sufficient to convert a low-pathogenicity influenza A virus infection into severe influenza disease that resembles ARDS, both histopathologically and transcriptionally. The IAV-infected Tpl2-/- mouse thereby represents a novel murine model for studying ARDS-like disease that could improve our understanding of this aggressive disease and assist in the design of better diagnostics and treatments.

A post-operative reaction to povidone­iodine in a postpartum woman: A case report.

Introduction: High infection rates after cesarean section are a major concern in the United States. A majority of antiseptics have irritant properties if they are not used as specified in companies' guidelines. Allergic contact dermatitis caused by povidone­iodine is infrequent and is misdiagnosed by clinicians who fail to differentiate allergy from irritation. This case report describes an allergic reaction to povidone­iodine after cesarean section. Case Presentation: A 28-year-old underwent a repeat low transverse cesarean-section at 39 weeks of gestation. The patient informed the medical team that she had no known allergies and no significant past medical history. The new hospital protocol included cleaning the skin over the planned incision site multiple times with povidone­iodine 7.5% scrub followed by povidone­iodine 10% paint. The surrounding skin was prepped with chlorhexidine. The patient complained of an allergic reaction on her skin the night after the procedure, with severe itching, and stated that it got progressively worse. The patient was started on an oral regimen of steroids and hydroxyzine. The itching slowly improved and at discharge the patient was continued on hydroxyzine and steroids were discontinued. By the patient's six-week postpartum visit, skin hypopigmentation had completely resolved. Conclusion: This case illustrates a reaction to povidone­iodine after cesarean section. This allergic reaction could not be attributed to any other portions of the procedure.

The Utility of Brain Natriuretic Peptide in Patients Undergoing an Initial Evaluation for Pulmonary Hypertension.

Introduction: Brain natriuretic peptide (BNP) is a polypeptide released from the cardiac ventricles and has been used as a diagnostic marker in cardiovascular diseases. Some patients with pulmonary hypertension have significant increases in BNP levels. This study wanted to determine whether the BNP levels in patients referred for evaluation of possible pulmonary hypertension were associated with a particular functional class or diagnostic group. Methods: Data were collected on patients from the Pulmonary Vascular Disease clinic undergoing right heart catheterization between 1/1/2019 and 5/20/2020. Clinical information, laboratory results including BNP, and hemodynamic parameters were recorded. Results: This study included 117 patients referred for evaluation for PH with measured BNP levels. The mean age was 63; the female to male ratio was 2:1, 25.4% of the patients were Hispanic. The average BNP level for the entire cohort was 4127.1 ± 11761.98 pg/ml. Patients in higher WHO functional classes tended to have higher levels of BNP, but statistical analysis BNP showed no differences between the functional classes. Patients in WHO Group 4 had significantly higher BNP levels than other WHO groups. Hemodynamic group classification demonstrated significant differences in BNP values between the low, intermediate, and high composite score patients. Conclusions: Patients undergoing evaluation for pulmonary hypertension had a wide range of BNP values. Patients with more abnormal composite hemodynamic scores higher BNP levels. Measurement of BNP provides an independent test to help interpret patients' descriptions of their functional limitations and to identify patients with more abnormal hemodynamic parameters.

Early outcomes of 21-gauge needle-guided ab interno tube sulcus placement of a non-valved implant in pseudophakic eyes.

We report the early outcomes and describe an ab interno 21-G needle technique of sulcus placement of the Aurolab aqueous drainage implant (AADI) tube in nine pseudophakic eyes. IOP reduced from a preoperative mean (SD) of 28.33 (9.80) to 11.56 (2.65) mm Hg and the mean (SD) number of preoperative medications reduced from 3.0 (0.7) to 0.4 (0.9) at 3 months. There were no intraoperative complications noted. This technique of sulcus placement of the AADI tube is a precise technique of tube insertion. It may be an alternative to existing ab externo procedures of tube sulcus placement, limiting multiple blind entries.

Clinical profile and long term outcomes of eyes with choroidal detachment following trabeculectomy.

Purpose: To assess the long-term outcomes of choroidal detachments (CDs) in eyes following trabeculectomy. Methods: Retrospective comparative case series. Data of patients with CDs following trabeculectomy (5-year period) with or without cataract surgery with a minimum of 3 months of follow-up were included. Results: In total, 45 patients with CDs following trabeculectomy were included. The mean age was 63.27 ± 8.68 years, (M:F = 2:1); 29 of 45 eyes (64.4%) had a baseline IOP of >24 mm Hg. Patients had a median follow-up of 22.2 (IQR: 16.2-30.5) months. Further, 10 of 45 eyes (22.2%) had CDs following suture lysis. The median onset of choroidal detachment from the time of surgery was 16.0 (IQR: 11-36) days. The mean BCVA improved from 0.62 ± 0.28 to 0.24 ± 0.27 (P < 0.001) and mean IOP increased from 4.07 ± 2.66 to 11.20 ± 5.31 (P < 0.001) at last visit. The cumulative success rates were 76.4% (95% CI: 48.4-90.5) in POAG eyes and 79.3% (95% CI: 62.8-89.1) in PACG eyes (P = 0.547). Medical management was the mainstay in all patients. Four of 45 (8.88%) patients underwent subsequent choroidal drainage. Conclusion: Choroidal detachment following modern-day trabeculectomy has favorable long-term visual acuity and IOP outcomes. There was no difference in the long-term surgical success of trabeculectomy with choroidal detachments in primary angle-closure and open-angle glaucoma eyes. Long-term follow-up is essential to prevent chronic hypotony and trabeculectomy failure.

Spontaneous peritoneal drainage following paracentesis in a hospitalized patient with resolution of type 1 hepatorenal syndrome.

The hepatorenal syndrome develops in a small percentage of patients with advanced liver disease. The pathogenesis involves intravascular volume contraction secondary to pooling of blood in the splanchnic vessels, stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone pathway, and increased intra-abdominal pressure secondary to the formation of large volumes of ascitic fluid. The treatment options are limited, and liver transplant is the only definitive form of management. Here we suggest an alternative approach to treating hepatorenal syndrome based on the unexpected continuous peritoneal drainage in a 36-year-old man hospitalized with hepatic encephalopathy and hepatorenal syndrome. A total of 11.2 L ascitic fluid drained over 5 days from a paracentesis puncture site with marked improvement in renal function; the creatinine decreased from 3.3 mg/dL to 0.7 mg/dL and the BUN decreased from 42 mg/dL to 10 mg/dL. The discussion with this case report summarizes the pathogenesis, including the effect of intra-abdominal pressure, of the hepatorenal syndrome, outlines medical management, and makes a proposal for clinical study based on this case.