Non-clotting factor therapies for preventing bleeds in people with congenital hemophilia A or B.

BACKGROUND: Management of congenital hemophilia A and B is by prophylactic or on-demand replacement therapy with clotting factor concentrates. The effects of newer non-clotting factor therapies such as emicizumab, concizumab, marstacimab, and fitusiran compared with existing standards of care are yet to be systematically reviewed. OBJECTIVES: To assess the effects (clinical, economic, patient-reported, and adverse outcomes) of non-clotting factor therapies for preventing bleeding and bleeding-related complications in people with congenital hemophilia A or B compared with prophylaxis with clotting factor therapies, bypassing agents, placebo, or no prophylaxis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, electronic databases, conference proceedings, and reference lists of relevant articles and reviews. The date of the last search was 16 August 2023. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating people with congenital hemophilia A or B with and without inhibitors, who were treated with non-clotting factor therapies to prevent bleeds. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed studies for eligibility, assessed risk of bias, and extracted data for the primary outcomes (bleeding rates, health-related quality of life (HRQoL), adverse events) and secondary outcomes (joint health, pain scores, and economic outcomes). We assessed the mean difference (MD), risk ratio (RR), 95% confidence interval (CI) of effect estimates, and evaluated the certainty of the evidence using GRADE. MAIN RESULTS: Six RCTs (including 397 males aged 12 to 75 years) were eligible for inclusion. Prophylaxis versus on-demand therapy in people with inhibitors Four trials (189 participants) compared emicizumab, fitusiran, and concizumab with on-demand therapy in people with inhibitors. Prophylaxis using emicizumab likely reduced annualized bleeding rates (ABR) for all bleeds (MD -22.80, 95% CI -37.39 to -8.21), treated bleeds (MD -20.40, 95% CI -35.19 to -5.61), and annualized spontaneous bleeds (MD -15.50, 95% CI -24.06 to -6.94), but did not significantly reduce annualized joint and target joint bleeding rates (AjBR and AtjBR) (1 trial; 53 participants; moderate-certainty evidence). Fitusiran also likely reduced ABR for all bleeds (MD -28.80, 95% CI -40.07 to -17.53), treated bleeds (MD -16.80, 95% CI -25.80 to -7.80), joint bleeds (MD -12.50, 95% CI -19.91 to -5.09), and spontaneous bleeds (MD -14.80, 95% CI -24.90 to -4.71; 1 trial; 57 participants; moderate-certainty evidence). No evidence was available on the effect of bleed prophylaxis using fitusiran versus on-demand therapy on AtjBR. Concizumab may reduce ABR for all bleeds (MD -12.31, 95% CI -19.17 to -5.45), treated bleeds (MD -10.10, 95% CI -17.74 to -2.46), joint bleeds (MD -9.55, 95% CI -13.55 to -5.55), and spontaneous bleeds (MD -11.96, 95% CI -19.89 to -4.03; 2 trials; 78 participants; very low-certainty evidence), but not target joint bleeds (MD -1.00, 95% CI -3.26 to 1.26). Emicizumab prophylaxis resulted in an 11.31-fold increase, fitusiran in a 12.5-fold increase, and concizumab in a 1.59-fold increase in the proportion of participants with no bleeds. HRQoL measured using the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) physical and total health scores was improved with emicizumab, fitusiran, and concizumab prophylaxis (low-certainty evidence). Non-serious adverse events were higher with non-clotting factor therapies versus on-demand therapy, with injection site reactions being the most frequently reported adverse events. Transient antidrug antibodies were reported for fitusiran and concizumab. Prophylaxis versus on-demand therapy in people without inhibitors Two trials (208 participants) compared emicizumab and fitusiran with on-demand therapy in people without inhibitors. One trial assessed two doses of emicizumab (1.5 mg/kg weekly and 3.0 mg/kg bi-weekly). Fitusiran 80 mg monthly, emicizumab 1.5 mg/kg/week, and emicizumab 3.0 mg/kg bi-weekly all likely resulted in a large reduction in ABR for all bleeds, all treated bleeds, and joint bleeds. AtjBR was not reduced with either of the emicizumab dosing regimens. The effect of fitusiran prophylaxis on target joint bleeds was not assessed. Spontaneous bleeds were likely reduced with fitusiran (MD -20.21, 95% CI -32.12 to -8.30) and emicizumab 3.0 mg/kg bi-weekly (MD -15.30, 95% CI -30.46 to -0.14), but not with emicizumab 1.5 mg/kg/week (MD -14.60, 95% CI -29.78 to 0.58). The percentage of participants with zero bleeds was higher following emicizumab 1.5 mg/kg/week (50% versus 0%), emicizumab 3.0 mg/kg bi-weekly (40% versus 0%), and fitusiran prophylaxis (40% versus 5%) compared with on-demand therapy. Emicizumab 1.5 mg/kg/week did not improve Haem-A-QoL physical and total health scores, EQ-5D-5L VAS, or utility index scores (low-certainty evidence) when compared with on-demand therapy at 25 weeks. Emicizumab 3.0 mg/kg bi-weekly may improve HRQoL measured by the Haem-A-QoL physical health score (MD -15.97, 95% CI -29.14 to -2.80) and EQ-5D-5L VAS (MD 9.15, 95% CI 2.05 to 16.25; 1 trial; 43 participants; low-certainty evidence). Fitusiran may result in improved HRQoL shown as a reduction in Haem-A-QoL total score (MD -7.06, 95% CI -11.50 to -2.62) and physical health score (MD -19.75, 95% CI -25.76 to -11.94; 1 trial; 103 participants; low-certainty evidence). The risk of serious adverse events in participants without inhibitors also likely did not differ following prophylaxis with either emicizumab or fitusiran versus on-demand therapy (moderate-certainty evidence). Transient antidrug antibodies were reported in 4% (3/80) participants to fitusiran, with no observed effect on antithrombin lowering. A comparison of the different dosing regimens of emicizumab identified no differences in bleeding, safety, or patient-reported outcomes. No case of treatment-related cancer or mortality was reported in any study group. None of the included studies assessed our secondary outcomes of joint health, clinical joint function, and economic outcomes. None of the included studies evaluated marstacimab. AUTHORS' CONCLUSIONS: Evidence from RCTs shows that prophylaxis using non-clotting factor therapies compared with on-demand treatment may reduce bleeding events, increase the percentage of individuals with zero bleeds, increase the incidence of non-serious adverse events, and improve HRQoL. Comparative assessments with other prophylaxis regimens, assessment of long-term joint outcomes, and assessment of economic outcomes will improve evidence-based decision-making for the use of these therapies in bleed prevention.

Utilization of a surgical database to provide care and assess perioperative treatment and outcomes in patients with bleeding disorders.

OBJECTIVES: To describe the Indiana Hemophilia and Thrombosis Center (IHTC) surgical database, its key components, and exploratory analyses of surgeries conducted between 1998 and 2019. METHODS: Surgical data across bleeding disorders collected retrospectively (1998-2006) and prospectively (2006-2019) were analyzed. Perioperative hemostasis, complications, and surgical plan deviations were compared by bleeding disorder diagnosis and data collection period. RESULTS: Within the 21-year period, 3246 procedures were conducted in 1413 patients with a diagnosis of von Willebrand disease (vWD), hemophilia A (HA), hemophilia B (HB), and other bleeding disorders. Majority of the procedures were minor (63.3%), and median number of surgeries per patient was 1 (range: 1-22). Adequate perioperative hemostasis was achieved in 90.9%, complications occurred in 13.6%, and surgical plan deviations occurred in 31.3% of procedures. Inadequate perioperative hemostasis and surgical plan deviations occurred more frequently in procedures involving HB compared with other bleeding disorders. Complications were not significantly different across bleeding disorders (p = .164). The prospective data collection period was associated with higher rates of hemostatic efficacy (92.4% vs. 88.3%; p < .001), complications (14.3% vs. 12.3%; p < .001), and plan deviations (34.2% vs. 25.1%; p < .001). CONCLUSION: The surgical database is an important resource in surgical management in patients with bleeding disorders. Further evaluation will facilitate use for the development of predictive models and principles of care.

Clotting factor concentrates for preventing bleeding and bleeding-related complications in previously treated individuals with haemophilia A or B.

BACKGROUND: The hallmark of severe hemophilia (A or B) is recurrent bleeding into joints and soft tissues with progressive joint damage, despite on-demand treatment. Prophylaxis has long been used, but not universally adopted, because of medical, psychosocial, and cost controversies. OBJECTIVES: To determine the effectiveness of clotting factor concentrate prophylaxis in managing previously-treated individuals with hemophilia A or B. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. In addition, we searched MEDLINE and Embase and online trial registries. Most recent search of Group's Coagulopathies Trials Register: 24 February 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating people with hemophilia A or hemophilia B, who were previously treated with clotting factor concentrates to manage their hemophilia. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed trials for eligibility, assessed risk of bias and extracted data. The authors used the GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: Ten trials (including 608 participants) were eligible for inclusion. Eight of the trials (477 participants) had arms comparing two or more prophylactic regimens to one another and four of the trials (n = 258) compared prophylaxis to on-demand treatment (two trials had multiple arms and were included in both comparisons). Comparison of two or more prophylactic regimens For trials comparing one prophylaxis regimen to another, given the heterogeneity of the data, none of the data were pooled for this comparison. Considering the individual trials, three trials reported the primary outcome of joint bleeding, and none showed a dfference between dosing regimens (low-certainty evidence). For the secondary outcome of total bleeding events, prophylaxis with a twice-weekly regimen of FIX likely results in reduced total bleeds compared to a once-a-week regimen of the same dose, mean difference (MD) 11.2 (5.81 to 16.59) (one trial, 10 participants, low-certainty evidence). Transient low-titer anti-FVIII inhibitors were reported in one of the trials. Blood-transmitted infections were not identified. Other adverse events reported include hypersensitivity, oedema, and weight gain. These were, however, rare and unrelated to study drugs (very low-certainty evidence). Comparison of prophylactic and on-demand regimens Four of the trials (258 participants) had arms that compared prophylaxis to on-demand treatment. Prophylaxis may result in a large decrease in the number of joint bleeds compared to on-demand treatment, MD -30.34 (95% CI -46.95 to -13.73) (two trials, 164 participants, low-certainty evidence). One of these trials (84 participants) also reported the long-term effects of prophylaxis versus on-demand therapy showing improved joint function, quality of life, and pain; but no differences between groups in joint structure when assessed by magnetic resonance imaging (MRI). In one trial (84 participants) validated measures for joint health and pain assessment showed that prophylaxis likely improves joint health compared to an on-demand regimen with an estimated change difference of 0.94 points (95% CI 0.23 to 1.65) and improves total pain scores, MD -17.20 (95% CI -27.48 to -6.92 (moderate-certainty evidence). Two trials (131 participants) reported that prophylaxis likely results in a slight increase in adverse events, risk ratio 1.71 (1.24 to 2.37) (moderate-certainty evidence). No inhibitor development and blood-transmitted infections were identified. Overall, the certainty of the body of evidence was judged to be low because of different types of bias that could have altered the effect.   AUTHORS' CONCLUSIONS: There is evidence from RCTs that prophylaxis, as compared to on-demand treatment, may reduce bleeding frequency in previously-treated people with hemophilia. Prophylaxis may also improve joint function, pain and quality of life, even though this does not translate into a detectable improvement of articular damage when assessed by MRI.  When comparing two different prophylaxis regimens, no significant differences in terms of protection from bleeding were found. Dose optimization could, however, result in improved efficacy. Given the heterogeneity of the data, pooled estimates were not obtained for most comparisons.  Well-designed RCTs and prospective observational controlled studies with standardised definitions and measurements are needed to establish the optimal and most cost-effective treatment regimens.

Tibia gap nonunion following sequestrectomy treated with a nonvascularized fibula strut graft.

Chronic osteomyelitis of the tibia is a common sequela of acute osteomyelitis which may present with a bone defect following sequestrectomy. Treatment of the gap nonunion can be done with the ipsilateral fibula as a strut graft when harvested subperiosteally and this leads to good outcome. A 7-year-old girl presented to our facility with a 25 cm defect of her right tibia following sequestrectomy for chronic osteomyelitis in another facility. X-rays revealed a healthy tibia superiorly and inferiorly with an intact fibula. She subsequently had an ipsilateral subperiosteal nonvascularized fibula harvest which was used to fill the tibia defect as a strut graft. The synostosis healed perfectly and the fibula reossified, time to union was 17 weeks, and the patient commenced full weight-bearing thereafter. Management of bone gap following sequestrectomy for chronic osteomyelitis remains a challenge to the orthopedic surgeon. The subperiosteal fibular harvest and use as a strut graft is a viable option with good outcomes. Our experience with this case may serve as a way out of this usual challenge.

Multimolecular assemblies on high surface area metal oxides and their role in interfacial energy and electron transfer.

High surface area metal oxides offer a unique substrate for the assembly of multiple molecular components at an interface. The choice of molecules, metal oxide, and the nature of the assembly method can have a profound influence on the mechanism, rate, and efficiency of photoinduced energy and electron transfer events at the interface. Owing to their diversity and high level of control, these interfacial assemblies are of interest for numerous applications including solar energy conversion, photoelectrosynthesis, photo-writable memory, and more. Although these assemblies are generated with very different goals in mind, they rely on similar surface binding motifs and molecular structure-property relationships. Therefore, the goal of this review is to summarize the various strategies (i.e. co-deposition, axial coordination, metal ion linkages, electrostatics, host-guest interactions, etc.) for assembling chromophores, hosts, electron donors/acceptors, and insulating co-adsorbent molecules on mesoporous metal oxide substrates. The assembly, synthesis, and characterization, as well as subsequent photoinduced events (i.e. cross-surface energy/electron transfer, interchromophore energy transfer, electron injection, and others) are discussed for the various assembly strategies.

Self-Assembled Bilayers on Nanocrystalline Metal Oxides: Exploring the Non-Innocent Nature of the Linking Ions.

Self-assembled bilayers on nanocrystalline metal oxide films are an increasingly popular strategy for modulating electron and energy transfer at dye-semiconductor interfaces. A majority of the work to date has relied on ZrII and ZnIV linking ions to assemble the films. In this report, we demonstrate that several different cations (CdII, CuII, FeII, LaIII, MnII, and SnIV) are not only effective in generating the bilayer assemblies but also have a profound influence on the stability and photophysical properties of the films. Bilayer films with ZrIV ions exhibited the highest photostability on both TiO2 and ZrO2. Despite the metal ions having a minimal influence on the absorption/emission energies and oxidation potentials of the dye, bilayers composed of CuII, FeII, and MnII exhibit significant excited-state quenching. The excited-state quenching decreases the electron injection yield but also, for CuII and MnII bilayers, significantly slows the back electron transfer kinetics.

Increasing the Open-Circuit Voltage of Dye-Sensitized Solar Cells via Metal-Ion Coordination.

Considerable efforts are dedicated to increasing the open-circuit voltage (Voc) of dye-sensitized solar cells (DSSCs) by slowing charge recombination dynamics using atomic layer deposition, alkyl-substituted dyes, coadsorbents, and other strategies. In this report, we introduce metal-ion coordination to a metal oxide bound dye as an alternative means of increasing Voc. Metal-ion coordination has minimal influence on the photophysical and electrochemical properties of the N3 dye, but presumably because of increased steric hindrance at the interface, it slows charge recombination kinetics and increases Voc by upwards of 130 mV relative to the parent N3 DSSC. With respect to the nature of the metal ion, the trend in decreasing short-circuit current (Jsc) and increasing Voc correlates with the charge of the coordinated metal ion (MIV → MIII → MII). We attribute this trend to electrostatic interactions between the metal cation and I- or I3-, with the more highly charged cations maintaining a higher concentration of mediator anions in proximity to the surface and, as a result, increasing the regeneration and recombination rates.

Metal ion mediated electron transfer at dye-semiconductor interfaces.

Here we demonstrate that the incorporation of Cu2+ linking ions into self-assembled bilayer films significantly perturbs the electron transfer rate at dye-semiconductor interfaces. Despite near unity quenching of the excited state of the dye by the Cu2+ ions, a charge separated state with slowed recombination is observed.

Cytisine for smoking cessation: A systematic review and meta-analysis.

BACKGROUND: Cytisine is a smoking cessation medication. This systematic review incorporates recently published randomized controlled trials (RCTs) to provide an updated evidence-based assessment of cytisine's efficacy and safety. METHODS: We searched Cochrane Library, MEDLINE, and EMBASE, for RCTs comparing cytisine to other smoking cessation treatments in adults who smoke. PRIMARY OUTCOME: 6-month biochemically verified continuous abstinence. Other outcomes: abstinence at longest follow-up, adverse events, mortality, and health-related quality of life (HRQOL). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess evidence certainty. RESULTS: We included 14 RCTs involving 9953 adults. Cytisine was superior to placebo (risk ratio [RR] 2.25, 95% confidence interval [CI] 1.13-4.47; 5 RCTs, 4325 participants), but not varenicline (RR 1.13, 95% CI 0.65-1.95; 2 RCTs, 2131 participants) for the primary outcome. Cytisine was superior to placebo (RR 2.78, 95% CI 1.64-4.70; 8 RCTs, 5762 participants) and nicotine replacement therapy [NRT] (RR 1.39, 95% CI 1.12-1.73; 2 RCTs, 1511 participants), but not varenicline (RR 1.02, 95% CI 0.72-1.44; 4 RCTs, 2708 participants) for abstinence at longest follow-up. Cytisine increased mostly gastrointestinal adverse events compared to placebo (RR 1.15; 95% CI 1.06-1.25; 8 RCTs, 5520 participants) and NRT (RR 1.52, 95% CI 1.26-1.84; 1 RCT, 1310 participants) but less adverse events compared to varenicline (RR 0.67; 95% CI 0.48-0.95; 3 RCTs, 2484 participants). CONCLUSION: Cytisine shows greater efficacy than placebo and NRT, but more adverse events. It is comparable to varenicline, with fewer adverse events. This can inform clinicians and guidelines on cytisine for smoking cessation.

Poverty, Health Care Access Barriers, and Functional Limitations among Individuals with Chronic Obstructive Pulmonary Disease: An 11-Year Cross-sectional Analysis, 2008-2018.

OBJECTIVES: To assess the relationship between poverty, delayed care, unaffordable care, and functional limitations among individuals with chronic obstructive pulmonary disease (COPD). METHODS: Using the National Health Interview Survey data, we selected respondents with COPD, aged 40 years and older. The predictor variables were poverty and measures of delayed and unaffordable care. The outcome variable was functional limitations. We performed a survey-weighted multivariate logistic regression analysis, adjusting for sociodemographic characteristics. RESULTS: Respondents classified as poor had three times the odds of functional limitations compared with those classified as not poor. Respondents who reported having measures of delayed care or unaffordable care had two to nine times and two to four times the adjusted odds of functional limitations compared with those who did not report such measures of delayed and unaffordable care, respectively. CONCLUSIONS: Poverty and delayed and unaffordable care are associated with functional limitations among individuals with COPD.

Inhibitors in hemophilia: association with surgery plans and outcomes in a retrospective cohort study.

Background: The development of antibodies (inhibitors) to clotting factors compromises the management of hemophilia A and B, resulting in resistance to clotting factor replacement and, in many cases, the need for bypassing agents to achieve hemostasis. Objectives: To evaluate the association between the presence of inhibitors and achievement of perioperative hemostasis, development of complications, and presurgical plan deviations. Methods: We conducted a retrospective study using data from the Indiana Hemophilia and Thrombosis Center surgical database (1998-2019). Associations between perioperative outcomes and inhibitor status were assessed while controlling for patient and procedural characteristics. Results: A total of 1492 surgeries were performed in 539 persons with hemophilia, with 72 procedures performed in 20 patients with inhibitors (15 with hemophilia A; 5 with hemophilia B). High-responding inhibitors (>5 BU/mL) were present in 27 procedures, low-responding inhibitors (≤5 BU/mL) were present in in 13 procedures, and 32 procedures were performed in patients with historically persistent inhibitors. Adjusting for age, diagnosis, surgery setting, hemostatic agent, data collection period, and surgery type (major/minor), inhibitors were associated with a higher risk of inadequate perioperative hemostasis (33.4% vs 8.6%; adjusted relative risk [adjRR], 3.78; 95% CI, 1.89-7.56; P < .001). Reported complications include hemorrhage, fever, pain, thrombosis, and infections. Complications were not statistically different based on inhibitor status (31.7% vs 14.6%; adjRR, 1.25; 95% CI, 0.63-2.49; P = .526). Presurgical plan deviations (eg, hemostatic medication dose adjustments, procedure rescheduling, and changes in the length of postoperative hospitalization) occurred more frequently in surgeries involving inhibitors (70.8 vs 39.5%; adjRR, 1.47; 95% CI, 1.12-1.93; P = .005). Conclusion: Inhibitors are associated with higher risks of adverse perioperative outcomes. Strategies to address inhibitor development should be prioritized to avoid undesirable perioperative outcomes.

Accidental Ingestion of a NEO-fit Device Component by a Neonate.

Background: Endotracheal tube securement devices are used to reduce the incidence of unplanned extubation of intubated patients. We describe the ingestion of part of an endotracheal tube securement device by a neonate to bring awareness of the risk of ingestion or aspiration of endotracheal tube securement device components in this population. Case Report: A 13-day-old, former 31-week gestational age female infant was noted on routine radiologic evaluation to have a foreign body in the gastrointestinal tract. The foreign body was thought to be an artifact or an object overlying the radiologic image. However, review of previous imaging showed the object initially in the posterior pharynx with progressive migration into the gastrointestinal tract. The patient did not have any clinical features of gastrointestinal obstruction and had been tolerating enteral feeds. The infant's endotracheal tube securement had been changed from a NEO-fit device (CooperSurgical, Inc.) to a NeoBar device (Neotech Products) on day of life 5. The diagnosis of the foreign body was made 8 days later. The infant was followed with serial imaging per pediatric surgery recommendations. The foreign body was spontaneously passed via the rectum several days later without incident. Pathology identified the foreign body as a piece of the NEO-fit device. Conclusion: Awareness of the possibility of ingestion or aspiration from this endotracheal tube securement device is important for patient safety.

Coagulation abnormalities in children with uncorrected congenital heart defects seen at a teaching hospital in a developing country.

BACKGROUND: Coagulation abnormality is a significant complication and cause of mortality in children with uncorrected congenital heart defects (CHD). The aim of this study was to determine the prevalence of coagulation abnormalities and the associated factors in children with uncorrected CHD. METHOD: A cross sectional study conducted to determine the prevalence of coagulation abnormalities among 70 children with uncorrected CHD aged six months to 17 years and 70 age and sex matched apparently healthy controls. Coagulation abnormalities was determined using complete blood count, prothrombin time, activated partial thromboplastin time and D-dimer assay. RESULTS: The prevalence of coagulation abnormalities among children with CHD and controls was 37.1% and 7.1% respectively. Children with Cyanotic CHD had a significantly higher prevalence of coagulation abnormalities compared to children with Acyanotic CHD (57.1% versus 17.1%). Haematocrit and oxygen saturation levels were significantly associated with coagulation abnormalities. CONCLUSION: This study affirms that coagulation abnormalities are frequent in children with uncorrected CHD. Oxygen saturation and haematocrit are risk factors of coagulation abnormalities. Routine coagulation screen is recommended especially in children with cyanotic congenital heart defects to improve their quality of life and reduce morbidity and mortality while awaiting definitive surgeries.

Allopurinol and valproic acid improve cardiac triglyceride and Na+-K+-ATPase activity independent of circulating aldosterone in female rats with glucose intolerance.

Context: Studies have shown that cardiac triglyceride accumulation and impaired Na+-K+-ATPase activity are linked to diabetes- related cardiovascular disease, particularly in women.Objectives: We hypothesised that allopurinol (ALL) and valproic acid (VPA) treatment would improve cardiac triglyceride and Na+-K+-ATPase activity independent of circulating aldosterone in Combined Oral Contraceptive (COC)-induced dysglycemiaMaterials and methods: Rats received COC (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel; po) with or without ALL (1 mg; po) and VPA (20 mg; po) for 6 weeks.Results: COC-treatment led to impaired glucose tolerance, accumulated abdominal fat, dyslipidemia, elevated plasma MDA, PAI-1 and aldosterone levels and also reduced plasma nitric oxide bioavailability and cardiac Na+-K+-ATPase activity. However, either ALL or VPA treatment ameliorated these alterations comparably independent of elevated aldosterone levelDiscussion and conclusion: Our results suggest that either ALL or VPA would improve cardiac TG and Na+-K+-ATPase activity comparably in COC-treated rats, regardless of circulating aldosterone level.

Comparison of Patient Clinical characteristics and Outcomes Between Different COVID-19 Peak Periods: A Single Center Retrospective Propensity Matched Analysis.

Introduction While Coronavirus disease 2019 (COVID-19) specific treatments have been instituted, overall mortality rates among hospitalized patients remain significant. Our study aimed to evaluate patient clinical characteristics and outcomes comparing the different COVID-19 infection peak periods. Methods This is a retrospective study of all adult patients hospitalized with a confirmed diagnosis of COVID-19 between March 1 to April 24, 2020 and November 1 to December 31, 2020, which corresponded to the first and second waves of COVID-19 infection in our institution, respectively. Demographic and clinical characteristics of the patients were compared and used for propensity matching. Clinical outcomes, such as need for intubation, renal replacement therapy and inpatient mortality were subsequently compared between the two groups. Results Patients in the second COVID-19 wave had a significantly higher body mass index (32.58 vs 29.83, p <0.001), as well as prevalence of asthma (14% vs 8%, p=0.019) and chronic kidney disease (42% vs 18%, p <0.001). Almost all patients in the second COVID-19 wave received corticosteroid treatment (99% vs 30%, p <0.001), and significantly more patients received remdesivir (43% vs 2%, p <0.001). Meanwhile, none of the patients in the second COVID-19 wave were treated with tocilizumab or hydroxychloroquine. Differences in clinical outcomes, such as need for renal replacement therapy or intubation, and median length of stay were not statistically significant. Inpatient mortality remained largely unchanged between the two COVID-19 peak periods. Discussion/ Conclusion In our institution, after propensity matched analysis, clinical outcomes such as need for renal replacement therapy, intubation and inpatient mortality remained unchanged between the two COVID-19 peak periods.

Post-Renal Biopsy Acute Kidney Injury and Page Kidney from Intra-Renal Hematoma Aggravated by Reversible Contrast-Induced Nephropathy Following Renal Arterial Embolization.

BACKGROUND Page kidney was described by Dr. Irving Page in animal kidneys in 1939 with renal failure and persistent arterial hypertension from "cellophane perinephritis". By 2009, about 100 cases of Page kidney had been reported. Bleeding complications after percutaneous kidney biopsy has, however, been well described. Moreover, the perioperative management of the recently introduced non-vitamin K antagonist anticoagulants (NOACs) remains uncertain due to inadequate evidence. Current guidelines to determine the appropriate duration of withholding NOACs before a surgical procedure, and when to restart NOACs safely after a procedure, however, cognizant of the implications of renal dysfunction, and levels of risk of the procedure are still unclear and sometimes conflicted. CASE REPORT We describe a case of Page kidney from an intrarenal hematoma complicating ultrasound-guided percutaneous right native kidney biopsy with acute kidney injury after withholding apixaban, a NOAC, for 3 days. Computed tomography evidence of continuing intrarenal bleeding from a renal pseudoaneurysm was treated with super-selective renal artery embolization; the case was further complicated by superimposed acute kidney injury from contrast-induced nephropathy. CONCLUSIONS We reviewed the vagaries of Page kidney with respect to the presence, or otherwise, of hypertension and how to explain worsening renal failure despite only unilateral involvement of a single kidney in a patient with 2 kidneys. Furthermore, we revisit the risks of contrast-induced nephropathy following iodinated contrast exposure. We explored the alternative management options for a post-biopsy renal pseudoaneurysm, that would avoid the use of iodinated contrast that could have potentially mitigated, if not fully prevented, the ensuing contrast-induced acute kidney injury.

Flavonols and an oxychromonol from Piliostigma reticulatum.

The leaf extract from the plant Piliostigma reticulatum was found to exhibit antimicrobial activity against some bacteria and fungi such as Staphylococcus aureus (NCTC 6571), Escherichia coli (NCTC 10418), Bacillus subtilis (NCTC 8236), Proteus vulgaris (NCTC 4175), Aspergillus niger (ATCC 10578) and Candida albicans (ATCC 10231). Upon investigation of the chemical constituents present in the leaf extract, a total of seven compounds were isolated and their structures were unambiguously established by spectroscopic methods including HR-MS and NMR spectrometry. Four of the isolated compounds were novel, namely 6-C-methyl-2-p-hydroxyphenyloxychromonol (piliostigmol), 1, 6,8-di-C-methylquercetin-3,3',7-trimethyl ether, 2, 6,8-di-C-methylquercetin-3,3'-dimethyl ether, 3 and 3',6,8,-tri-C-methylquercetin-3,7-dimethyl ether, 4. The other three were known C-methylated flavonols and they were isolated from P. reticulatum for the first time. These were 6-C-methylquercetin-3-methyl ether, 5, 6,8-di-C-methylkaempferol-3-methyl ether, 6 and 6-C-methylquercetin-3,3',7-trimethyl ether 7. All the isolated compounds were tested for cytotoxicity using the brine shrimp toxicity assay and all of them were active albeit at different levels. With respect to antibacterial activity piliostigmol, 1 showed the highest activity against E. coli (MIC=2.57 microg/ml, 0.006 micromol), which is three times more that of Amoxicillin, where as 4 and 7 showed the least activity.

Energy and Electron Transfer Cascade in Self-Assembled Bilayer Dye-Sensitized Solar Cells.

Current high efficiency dye-sensitized solar cells (DSSCs) rely on the incorporation of multiple chromophores, via either codeposition or preformed assemblies, as a means of increasing broad band light absorption. These strategies have some inherent limitations including decreased total light absorption by each of the dyes, low surface loadings, and complex synthetic procedures. In this report, we introduce an alternative strategy, self-assembled bilayers, as a simple, stepwise method of incorporating two complementary chromophores into a DSSC. The bilayer devices exhibit a 10% increase in Jsc, Voc, and η over the monolayer devices due to increased incident photon-to-electron conversion efficiency across the entire visible spectrum and slowed recombination losses at the interface. Directional energy and electron transfer toward the metal oxide surface are key steps in the bilayer photon-to-current generation process. These results are important as they open the door to a new architecture for harnessing broadband light in dye-sensitized devices.

Inhibiting Interfacial Recombination Events in Dye-Sensitized Solar Cells using Self-Assembled Bilayers.

The rate and efficiency of electron transfer events at the semiconductor-dye-electrolyte interface is of critical importance to the overall performance of dye-sensitized solar cells (DSSCs) and dye-sensitized photoelectrosynthesis cells. In this work, we introduce self-assembled bilayers composed of a metal oxide electrode, bridging molecules, linking ions, and dye as an effective strategy to manipulate interfacial electron transfer events at the photoanode of DSSCs. Spectroelectrochemical measurements including current-voltage, incident photon-to-current efficiency, and electrochemical impedance spectroscopy are used to quantify interfacial electron transfer and transport events with respect to the length of the bridging molecules. The general trend in increased lifetime and diffusion length in TiO2 as well as an increase in open circuit voltage with bridge length indicate that the bilayer is an effective strategy in inhibiting the TiO2(e(-)) to redox mediator recombination events. However, the increased separation between the dye and the semiconductor also reduces the electron injection rate resulting in a decrease in photocurrent as the bridge length increases. The observed enhancement in open circuit voltages are far outweighed by the significant decrease in photocurrent and thus overall device performance decreases with increasing bridge length.