Reversible CO2 Capture and On-Demand Release by an Acidity-Matched Organic Photoswitch.

Separation of carbon dioxide (CO2) from point sources or directly from the atmosphere can contribute crucially to climate change mitigation plans in the coming decades. A fundamental practical limitation for the current strategies is the considerable energy cost required to regenerate the sorbent and release the captured CO2 for storage or utilization. A directly photochemically driven system that demonstrates efficient passive capture and on-demand CO2 release triggered by sunlight as the sole external stimulus would provide an attractive alternative. However, little is known about the thermodynamic requirements for such a process or mechanisms for modulating the stability of CO2-derived dissolved species by using photoinduced metastable states. Here, we show that an organic photoswitchable molecule of precisely tuned effective acidity can repeatedly capture and release a near-stoichiometric quantity of CO2 according to dark-light cycles. The CO2-derived species rests as a solvent-separated ion pair, and key aspects of its excited-state dynamics that regulate the photorelease efficiency are characterized by transient absorption spectroscopy. The thermodynamic and kinetic concepts established herein will serve as guiding principles for the development of viable solar-powered negative emission technologies.

Use of adjunctive topical corticosteroids in bacterial keratitis.

PURPOSE OF REVIEW: Topical corticosteroid use in the setting of infectious keratitis has been a controversial issue. The aim of this review is to provide an update on the evidence for use of topical corticosteroids in addition to antibiotics in bacterial keratitis. RECENT FINDINGS: Judicious use of steroids is postulated to limit the inflammatory component of bacterial keratitis, but can theoretically retard healing. Three small randomized controlled trials and one large-scale trial, the Steroids for Corneal Ulcers Trial, have provided the most recent evidence to address this debate. Adjunctive topical corticosteroids initiated after at least 48 h of antibiotic usage in cases of culture-proven bacterial keratitis appear generally safe in the treatment of bacterial keratitis. They may be beneficial in cases of severe ulcers especially when initiated early in the course of the infection, in non-Nocardia ulcers, and in certain Pseudomonas ulcers. SUMMARY: Several randomized controlled trials have greatly contributed to our understanding of the controversy over steroid use in the management of bacterial keratitis. Future studies are needed to confirm subgroup analysis findings and define optimal timing, dosage, and the most appropriate treatment populations.

Femtosecond laser-assisted cataract surgery in residency training.

PURPOSE OF REVIEW: To examine the current state of femtosecond laser-assisted cataract surgery (FLACS) with a focus on its incorporation into resident surgical education. RECENT FINDINGS: To date, there are no published data on FLACS in residency training programs. Teaching FLACS concurrently with manual cataract surgery can theoretically allow a trainee to become proficient in both domains and to navigate the complexities and complications of both procedures in a dedicated learning environment. SUMMARY: Early reports from completed projects at our institution suggest that incorporating FLACS into residency education is successful and well tolerated. The procedure appears to have a similar safety profile and delivers similar refractive results compared with conventional phacoemulsification cataract surgery, even during the initial surgical learning curve. More research needs to be carried out on the safety profile and outcomes of resident performed FLACS and its ultimate role in trainee education.

FDA Approval Summary: Oral Azacitidine for Continued Treatment of Adults with Acute Myeloid Leukemia Unable to Complete Intensive Curative Therapy.

On September 1, 2020, the FDA granted approval for oral azacitidine (Onureg, CC-486) for continued treatment of adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and who are not able to complete intensive curative therapy. Approval was based on improvement in overall survival using CC-486 300 mg daily in a 2 weeks on/2 weeks off schedule in comparison with placebo (HR, 0.69; 95% confidence interval, 0.55-0.86; P = 0.0009) in the randomized trial CC-486-AML-001 (QUAZAR) in adults ≥ 55 years old with AML in CR/CRi who did not complete standard intensive induction and postremission therapy. Of note, the study was not designed to test CC-486 as maintenance after standard postremission therapy or as an alternative to standard postremission therapy. Gastrointestinal toxicities, fatigue, and pneumonia were more common in patients treated with CC-486 compared with placebo. Additional studies are needed to establish safe dosing for patients with hepatic impairment. The pharmacokinetic parameters, recommended dose, and recommended schedule of CC-486 differ substantially from those of other azacitidine formulations; therefore, inappropriate substitutions between formulations pose a considerable risk for harm.

Current concepts in the management of periocular infantile (capillary) hemangioma.

PURPOSE OF REVIEW: To review and evaluate the medical literature on new treatments for periocular infantile (capillary) hemangioma. Recent studies have shown a promising new therapy for infantile hemangioma using nonselective ß-blockers, including oral propranolol and topical timolol. RECENT FINDINGS: Conventional treatments for infantile hemangioma include the use of corticosteroids, laser, surgery, and immunomodulator therapy. Recently, systemic and topical ß-blockers have been used to successfully treat infantile hemangioma. The drugs' mechanism of action remains uncertain, but plausible theories include vasoconstriction, modulation of pro-survival signal transduction pathways, and endothelial cell apoptosis. Whereas no life-threatening adverse events from ß-blocker treatment have been described, there have been reports of bradycardia, hypotension, bronchospasm, hypoglycemia, and electrolyte disturbances resulting from systemic use of propranolol to treat infantile hemangioma. Sleep and gastrointestinal disturbances have also been frequently reported. Topical timolol application for localized, superficial tumors may confer similar efficacy as oral propranolol while reducing systemic effects. SUMMARY: Despite the recent explosion of interest surrounding this novel treatment, current treatment and protocol-monitoring recommendations are based largely on the experience of individual centers. Several randomized controlled studies are currently underway, the results of which will guide future standard-of-care treatment for infantile hemangioma.

Identification of phase boundaries in anhydrate/hydrate systems.

Near-infrared spectroscopy was used to monitor the phase conversion for two solvatomorphs of caffeine, an anhydrous form and a nonstoichiometric hydrate, as a function of time, temperature, and relative humidity. The transformation kinetics between these caffeine forms was determined to increase with temperature. The rate of conversion was also determined to be dependent on the difference between the observed relative humidity and the equilibrium water activity of the anhydrate/hydrate system, that is, phase boundary. Near the phase boundary, minimal conversion between the anhydrous and hydrated forms of caffeine was detected. Using this kinetic data, the phase boundary for these forms was determined to be approximately 67% RH at 10 degrees C, 74.5% RH at 25 degrees C, and 86% RH at 40 degrees C. At each specified temperature, anhydrous caffeine is the thermodynamically stable form below this relative humidity and the hydrate is stable above. The phase boundary data were then fitted using a second order polynomial to determine the stability relationship between anhydrous caffeine and its hydrate at additional temperatures. This approach can be used to rapidly determine the stability relationship for solvatomorphs as well as the relative kinetics of their interconversion. Both of these factors are critical in selecting the development form, designing appropriate stability studies, and developing robust conditions for the preparation and packaging of the API and formulated drug product.

Outcomes After Descemet Stripping Automated Endothelial Keratoplasty in Patients With Glaucoma Drainage Devices.

PURPOSE: To evaluate outcomes after Descemet stripping automated endothelial keratoplasty in eyes with glaucoma drainage devices. METHODS: This is a retrospective review of 24 cases performed by a single surgeon (S.B.H.) on 20 eyes. Data were gathered on demographics, ocular history, surgical details, and postoperative outcomes. Outcome measures included primary graft failure, secondary graft failure, endothelial cell density (ECD), central corneal thickness (CCT), intraocular pressure, and visual acuity. RESULTS: With a mean follow-up of 30.3 ± 19.6 months, there was no occurrence of primary graft failure, and the rate of secondary graft failure was 29%. Survival rates at 1, 2, and 3 years, respectively, were 87% [95% confidence interval (CI): 65%-96%], 80% (95% CI: 55%-92%), and 70% (95% CI: 39%-88%). Compared with ECD of the donor lenticule, endothelial cell loss was 49 ± 16% (n = 21) at postoperative month 3, 59 ± 16% (n = 20) at month 6, 61 ± 20% (n = 16) at month 12, and stabilized at 75 ± 17% (n = 9) by month 18. Compared with CCT during the visit before surgery, CCT decreased to 83 ± 18% (n = 18) at postoperative month 3 and gradually increased to 95 ± 11% (n = 6) at month 24. There were 4 (17%) cases of intraocular pressure elevation above 25 mm Hg. Improved visual acuity occurred in 71% of patients. CONCLUSIONS: Descemet stripping automated endothelial keratoplasty in eyes with corneal edema secondary to endothelial dysfunction in the presence of a previous glaucoma drainage device is a successful procedure. However, intermediate term endothelial cell loss is significant, as is the graft failure rate.

Epithelial Downgrowth after Intraocular Surgery Treated with Intracameral 5-Fluorouracil.

Purpose. To present the clinical and histopathologic correlation of two cases of epithelial downgrowth (EDG) after prior intraocular surgery. Methods. Observational case reports. Results. We present two cases of EDG occurring after intraocular surgery. In both cases, after two anterior chamber injections of 5-fluorouracil (5FU), the area of EDG initially regressed. In Case 1, a limited area of EDG eventually recurred, and penetrating keratoplasty with cryotherapy was curative. In Case 2, subsequent corneal edema required Descemet-stripping automated endothelial keratoplasty, and the patient remained clinically free of EDG without further treatment. Conclusion. Intracameral 5FU may have a role in the treatment of EDG after intraocular surgery, though its precise utilization and impact remain to be defined.

Seasonal, geographic, and antimicrobial resistance patterns in microbial keratitis: 4-year experience in eastern Pennsylvania.

PURPOSE: The aim of this study was to review the demographics, causative organisms, seasonal and geographic variation, and antimicrobial resistance patterns of microbial keratitis at our institution over a 4-year period. METHODS: Electronic medical records of all patients with microbial keratitis who underwent corneal culturing at a single institution in eastern Pennsylvania between January 1, 2009 and December 31, 2012 were reviewed. RESULTS: A total of 311 patients representing 323 instances of infectious keratitis were analyzed. The most frequently implicated organisms in contact lens-related infections were Pseudomonas aeruginosa for bacteria and Fusarium species for fungus, compared with Staphylococcus aureus and Candida species in non-contact lens-associated bacterial infections. Bacterial keratitis occurred most frequently in spring and least frequently in winter (P = 0.024). Patients who live in large fringe metro (suburban) areas accounted for the highest proportion of infectious keratitis cases. P. aeruginosa and methicillin-sensitive S. aureus isolates were highly susceptible to fluoroquinolones, whereas 32% of coagulase-negative staphylococcus isolates tested were resistant to moxifloxacin and gatifloxacin, and all methicillin-resistant S. aureus organisms tested were resistant to these 2 fluoroquinolones. No organisms tested were resistant to tobramycin, gentamicin, or vancomycin. No fungal infections tested were resistant to voriconazole. CONCLUSIONS: Most infectious keratitis occurred in nonwinter months and in patients from suburban counties. Although fluoroquinolones were effective against the most common bacteria, staphylococcal species exhibited a high rate of resistance, representing a therapeutic challenge given the increasing use of fluoroquinolones as first-line monotherapy. No organisms tested were resistant to tobramycin, gentamicin, vancomycin, or voriconazole.

Prediction of Setschenow constants.

The Setschenow (salting out) constant by sodium chloride is related to molar volume, aqueous solubility, and octanol-water partition coefficient, K(ow), of the drug solute. This study validates a previously proposed relationship between the salting out constant of a solute and its partition coefficient. It also shows that the partition coefficient is a better descriptor of salting out than either molar volume or solubility.

Solubilization and preformulation of carbendazim.

The solubilization of carbendazim by pH in combination with cosolvents, surfactants or complexants was investigated. At pH 7 the total drug solubility is 6.11 +/- 0.45 microg/ml which increases by 1-7 fold with cosolvent, surfactant or complexant. However, at pH 2 the solubility increases by 250 times. Cosolvents have a negligible effect (50% increase) on the total drug solubility at pH 2 because of the high polarity of the cationic drug. Also pH combined with nonionic surfactants does not improve solubility, as relatively less polar micelles are not able to accommodate the cationic drug. Interestingly, the total drug solubility increases by combining pH 2 with complexants, as they can form a complex with the isolated aromatic ring of both the unionized and the ionized drug. The proposed oral formulation of 1 mg/ml carbendazim at pH 2 does not precipitate in the presence of Seven Up or water. But it does precipitate with pH 7 buffer when diluted 1:10 but not 1:100 or 1:250.

Stabilization and preformulation of anticancer drug--SarCNU.

The stability of SarCNU (NSC364432), 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea in several pharmaceutically acceptable solvents was investigated by high pressure liquid chromatography (HPLC). The influences of light, ionic strength, pH, buffer concentration, and the following excipients: benzyl alcohol, ascorbic acid, sodium bisulfite, and disodium EDTA were studied at room temperature. The stability of the drug was also determined in water, EtOH, PG, Capmul PG, DMSO, and in different combinations of these cosolvents at four different temperatures. The degradation of the drug, which is catalyzed not only by general but also by specific acid and base, follows first order kinetics. Antioxidants, EDTA, and light have no effect on the degradation rate, suggesting oxidation is not a major degradation pathway. The t(90) in pure cosolvent is 25-50 times higher than that in water or semi-aqueous vehicles. Neat EtOH can be used to store the drug in a nonaqueous concentrate that is diluted with aqueous solvent prior to injection.

Elevation of intraocular pressure in glaucoma patients after automated visual field testing.

PURPOSE: To examine whether automated visual field (VF) testing may exert a short-term influence on subsequent intraocular pressure (IOP) measurement during the same visit. METHODS: We reviewed patients with primary open-angle glaucoma whose most recent visit occurred at a major academic institution from July to December 2009 and who had 3 visits without intervening changes in glaucoma management within the previous 5 years. Exclusion criteria were patient admittance of nonadherence with medical therapy and documented difficulty of IOP measurement. One hundred nine right eyes from 109 patients were included. IOP obtained within 30 minutes after VF testing was compared with IOP from the previous and next visits without VF testing. Subgroup analyses included the role of reliability of VF test performance, surgical versus medical IOP control, and different topical medications. RESULTS: The average IOP measured after VF testing was 14.9 ± 4.7 mm Hg, higher than both the previous (13.7 ± 4.4 mm Hg, P < 0.001) and next visits without VF examination (13.8 ± 4.4 mm Hg, P < 0.001). A total of 22.9% of patients experienced a more than 20% increase of IOP. Eyes with surgical control had less IOP elevation than eyes with medical control (3.1% ± 15.9% vs. 11.7% ± 17.4%, P = 0.009). Users of ß-blockers or α-2-agonists had less IOP elevation than eyes controlled with prostaglandins or carbonic anhydrase inhibitors (0.9% ± 15.1% vs. 9.0% ± 12.3%, P = 0.030). CONCLUSIONS: This retrospective study suggests that patients with primary open-angle glaucoma experience a small and transient increase in IOP after VF testing and that this effect may be lower after surgical pressure control.

New developments in the management of periocular capillary hemangioma in children.

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder.

Association between disruption of fibrin sheaths using percutaneous transluminal angioplasty balloons and late onset of central venous stenosis.

To compare the rates of central venous stenosis in patients undergoing hemodialysis who underwent disruption of fibrin sheath with percutaneous transluminal angioplasty balloons and those who underwent over-the-wire catheter exchange. This study is a retrospective review of 209 percutaneous transluminal angioplasty balloon disruption and 1304 over-the-wire catheter exchange procedures performed in 753 patients. Approval from the Human Investigations Committee was obtained for this study. Up to 10-year follow-up was performed. A χ(2) test was used to compare the rates of central venous stenosis after balloon disruption versus catheter exchange. A t-test was used to compare time to central venous stenosis development. Of the 753 patients in the study, 127 patients underwent balloon disruption of fibrin sheath and 626 had catheter exchange. Within the balloon disruption group, 18 (14.2%) of 127 patients subsequently developed central venous stenosis, compared with 44 (7.0%) of 626 in the catheter exchange group (P < 0.01, χ(2) test). Time to central venous stenosis development was approximately 3 years in both groups and not significantly different (1371 and 1010 days, P = 0.20). A total of 25.2% of patients in the balloon disruption group had four or more subsequent catheter exchanges, versus 12.6% in the catheter exchange group (P < 0.01, χ(2) test). In conclusions, there is a possible association between percutaneous transluminal angioplasty balloon disruption of fibrin sheath and late-onset central venous stenosis. Because venography was not routinely performed in catheter exchange patients, future randomized studies are necessary to confirm these findings.

Complete regression of retinoblastoma following intra-arterial chemotherapy.

A 22-month-old girl with Group C unilateral retinoblastoma demonstrated dramatic tumor regression after two infusions of 5 mg of intra-arterial melphalan as primary therapy. Complete tumor control without recurrence was noted at 1 year. Retinal and choroidal perfusion was intact and the electroretinogram improved following therapy.

Initial clinical experience with a new heparin-coated chronic hemodialysis catheter.

In this paper we wish to report our clinical experience with a new heparin-coated dialysis catheter with a symmetric tip. Over a 16-month period, 60 heparin-coated Tal Palindrome catheters were placed in 57 patients. Catheter patency, catheter-related complications, and reasons for catheter removal were recorded. The patient's initial cause of end-stage renal disease, underlying diseases, and site of access were recorded as well. Patients were specifically followed for development of heparin-induced thrombocytopenia. Patient ages were 34-91 (average 66). Fifty-four percent of patients had a history of diabetes. Sixty catheters were placed for a total of 5353 catheter-days. The average catheter indwell time was 107 days (range of 2-381 days). Catheter-related infection occurred in 6 patients over the study period, with a rate of 1.12/1000 catheter-days. Bacteremia occurred in 3 patients with a rate of 0.56/1000 catheter-days. Six catheters were removed or exchanged due to malfunction. There was no incidence of heparin-induced thrombocytopenia. Initial clinical experience with the heparin-coated Tal Palindrome hemodialysis catheter demonstrated safe, reliable use, and low infection rates.

Sustained release subcutaneous delivery of BMS-686117, a GLP-1 receptor peptide agonist, via a zinc adduct.

BMS-686117 is an 11-mer GLP-1 receptor agonist with a short intrinsic pharmacokinetic half-life (t(1/2)) of approximately 2h. In order to develop an extended release formulation for once-daily (QD) subcutaneous administration, a non-covalently bonded Zn/BMS-686117 adduct with very low aqueous solubility was prepared through mixing zinc acetate and BMS-686117 solutions, followed by filtration or spray drying. At pH 6.8, free BMS-686117 concentration decreased continuously with the increase of Zn:BMS-686117 ratio. Furthermore, free BMS-686117 concentration increases in the presence of ethylenediaminetetraacetic acid (EDTA), indicating the reversibility of the zinc-peptide association. As solids, the glass transition temperature of Zn/BMS-686117 adduct increases with the increase of Zn:BMS-686117 ratio. A Zn/BMS-686117 adduct suspension, with a molar ratio of zinc:BMS-686117 of 3:1, was dosed subcutaneously to dogs along with two other solution formulations. The Zn/BMS-686117 adduct showed a prolonged BMS-686117 terminal t(1/2) of 8.5h, a mean residence time (MRT) of 16h, and a C(max) value 6-8 times lower than the solution formulations. Additionally, the Zn/BMS-686117 was encapsulated into poly(lactide-co-glycolide) (PLGA) microspheres. The Zn/BMS-686117 microspheres showed an almost zero-order release profile in vitro for at least 18 days, with minimal initial burst, indicating the potential of using this approach for long-term sustained release.

Selecting optimal hemodialysis catheters: material, design, advanced features, and preferences.

Hemodialysis catheters are a necessary evil. They provide an immediate and effective lifeline for hemodialysis patients, and their use is steadily increasing. This increasingly important role has lead to the development of many generations of dialysis catheters. Some aspects of novel designs have shown potential to reduce complications, while others provide options for physician insertion preference. The two major biomaterials for catheter construction are currently polyurethane and silicone, while copolymers such as carbothane are becoming more widespread. Catheter coatings such as heparin, antibiotics, and silver ion are designed to minimize thrombosis and infection. Finally, many lumen and tip designs are also available. These new features were designed to address common problems, including maintenance of adequate flow rate and prevention of thrombosis, fibrin sheath, and catheter-related infection. However, reliable data directly comparing these different designs and coatings are currently lacking. This communication reviews current hemodialysis catheters, including materials, design, and advanced features.