Management of Aspirin-Exacerbated Respiratory Disease: What Does the Future Hold?

Aspirin-exacerbated respiratory disease (AERD) is a subtype of chronic rhinosinusitis with polyps (CRSwNP) and asthma with higher recurrence of nasal polyps after surgery and severe asthma. Patients with CRSwNP and asthma should be screened for AERD by detailed history of aspirin/nonsteroidal anti-inflammatory drug reactions and review of medications that may mask aspirin reaction or directly by aspirin challenge. Treatment of AERD may require more intensive therapy, including endoscopic sinus surgery, daily aspirin therapy, leukotriene modifiers, or biologics.

Improved Efficiency and Stability in 1,5-Diaminonaphthalene Iodide-Passivated 2D/3D Perovskite Solar Cells.

Engineering multidimensional two-dimensional/three-dimensional (2D/3D) perovskite interfaces as light harvesters has recently emerged as a potential strategy to obtain a higher photovoltaic performance in perovskite solar cells (PSCs) with enhanced environmental stability. In this study, we utilized the 1,5-diammonium naphthalene iodide (NDAI) bulky organic spacer for interface modification in 3D perovskites for passivating the anionic iodide/uncoordinated Pb2+ vacancies as well as facilitating charge carrier transfer by improving the energy band alignment at the perovskite/HTL interface. Consequently, the NDAI-treated 2D/3D PSCs showed an enhanced open-circuit voltage and fill factor with a remarkable power conversion efficiency (PCE) of 21.48%. In addition, 2D/3D perovskite devices without encapsulation exhibit a 77% retention of their initial output after 1000 h of aging under 50 ± 5% relative humidity. Furthermore, even after 200 h of storage in 85 °C thermal stress, the devices maintain 60% of their initial PCE. The defect passivation and interface modification mechanism were studied in detail by UV vis absorption, photoluminescence spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), ultraviolet photoelectron spectroscopy (UPS), solid-state NMR, space-charge-limited current (SCLC) mobility measurement, and impedance spectroscopy. This study provides a promising path for perovskite surface modification in slowing their degradation against external stimuli, providing a future direction for increasing the perovskite device efficiency and durability.

Perioperative management of mastocytosis.

PURPOSE: Patients with mastocytosis have an increased risk of anaphylaxis during surgical procedures with general anesthesia. Therefore, we reviewed the anesthesia course of a large cohort of patients with mastocytosis. METHODS: We retrospectively reviewed adult and pediatric patients with mastocytosis who underwent surgical procedures with general anesthesia at Mayo Clinic from January 1, 2000, through June 30, 2021. We also included any procedures with general anesthesia that occurred during the 3-year period preceding mastocytosis diagnosis and designated the patients who underwent these procedures as having an unknown diagnosis at the time of their surgical procedure. We analyzed whether patients received chronic antimediator treatment for mastocytosis and/or prophylactic medications before the procedures. We also determined whether medications indicative of mastocytosis-related adverse events were intraoperatively administered. RESULTS: We identified 113 patients who underwent 219 procedures during the study period; 25 procedures were performed before mastocytosis diagnosis. Of 194 procedures in patients with known mastocytosis, patients received chronic antimediator therapy and/or perioperative prophylactic medications for 178 (91.8%) procedures. Among these procedures, 10 were potentially complicated by mast cell activation, which was inferred from administration of inhaled albuterol (n = 3) or intravenous diphenhydramine (n = 8). In addition, there was only one case of intraoperative anaphylaxis which occurred in a patient who underwent anesthesia before mastocytosis diagnosis and therefore did not receive prophylaxis. CONCLUSION: Intraoperative anaphylaxis can be the first presenting sign of mastocytosis. Patients with mastocytosis who received chronic antimediator therapy and/or preoperative prophylactic medications had an uneventful surgical course.

Seasonal variability in size-resolved hygroscopicity of sub-micron aerosols over the Western Ghats, India: Closure and parameterization.

Hygroscopicity of atmospheric aerosol primarily depends on the size and chemical composition of the particle and is important for estimating anthropogenic aerosol radiative forcing. There is limited information exists over the Indian region on size segregated aerosol hygroscopicity (κ) in different seasons. This study presents 'κ' as derived from a Humidified Tandem Differential Mobility Analyzer (HTDMA) over a High Altitude Cloud Physics Laboratory (HACPL) in the Western Ghats, India for more than a year (from May 2019 to May 2020). The average hygroscopicity values of aerosol particles of diameters 32, 50, 75, 110, 150, 210 and 260 nm at 90 % RH condition are 0.19, 0.18, 0.16, 0.17, 0.18, 0.20, 0.21 respectively during the entire observation period. κ was observed to decrease with an increase in size in the Aitken mode regime (32-75 nm) and an increase in the accumulation mode (110-260 nm). Seasonal variation of hygroscopicity for a wide range of particle diameters is reported which is highly demanding as there is a change in the air mass flow pattern in each of the seasons. The diurnal cycle of hygroscopicity showed a prominent peak during the midnight to early morning hours followed by a decrease in the forenoon hours and a secondary peak in the afternoon hours. κ is found to be higher in pre-monsoon compared to winter season as Chl is approximately 3 % higher in pre-monsoon and NH4Cl is highly hygroscopic among the assumed chemical composition. Hygroscopicity derived through chemical speciation observations assuming internal and external mixing of aerosols i.e. κinter and κexter are overestimating as compared to κHTDMA. However, the bias between kexter and kHTDMA is relatively lower as external mixing type of aerosol is evident through the growth factor data sets measured by HTDMA. Utilizing the hygroscopicity measurements available for discrete diameters by HTDMA, a parameterization of hygroscopicity with the dry diameter of sub-micron particles is developed.

Unified Airway Disease: Diagnosis and Subtyping.

The concept of a unified airway posits that pathology affects the respiratory tract in a continuum and that disease in one part of the respiratory tract may be associated with or directly or indirectly affect the function of a different part. Transcriptomic analysis has shown 91% homology between the genes expressed in the upper and the lower airway. Approaching inflammatory airway disorders using the unified airway hypothesis allows for a better clarification of disease process and provides a detailed and a high-level overview of dysfunction. There are several tools available to the clinician to use to subtype and diagnose accurately the abnormal pathways operating in inflammatory airway disorders. These tools include clinical history, physical examination findings, imaging (computed tomography and MRI), allergy and laboratory testing, pulmonary function testing (PFT), and tissue histopathology. Tests can be categorized based on platform, by specimen, or the marker being studied.

Aspirin-Exacerbated Respiratory Disease and the Unified Airway: A Contemporary Review.

Aspirin-exacerbated respiratory disease (AERD) is characterized by abnormal arachidonic acid metabolism leading to chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and upper and/or lower respiratory symptoms after ingestion of cyclooxygenase-1 inhibiting nonsteroidal antiinflammatory drugs. Diagnosis is clinical and may involve an aspirin challenge. Inflammatory biomarkers may be useful for diagnosis and treatment monitoring. Conventional medical management for asthma and CRSwNP is often inadequate. Endoscopic sinus surgery followed by continued medical management with or without aspirin desensitization frequently improves symptoms and objective disease measures. Biological agents targeting eosinophilic inflammation are promising alternatives to conventional management.

Efficacy and Safety of Pregabalin Prolonged Release-Etoricoxib Combination Compared to Etoricoxib for Chronic Low Back Pain: Phase 3, Randomized Study.

INTRODUCTION: Currently available treatments for chronic lower back pain (CLBP) do not adequately address both nociceptive and neuropathic components of pain. We evaluated efficacy and safety of fixed-dose combination (FDC) of low-dose pregabalin prolonged release 75 mg-etoricoxib 60 mg to address both pain components. METHODS: This randomized phase 3 trial conducted at 12 centres across India evaluated efficacy (based on mean change in numeric rating scale [NRS], Roland-Morris disability questionnaire [RDQ], visual analogue scale [VAS], patient global impression of improvement [PGI-I], clinical global impression of improvement [CGI-I] and rescue medication consumption) and safety of FDC in comparison to etoricoxib alone in adult patients with CLBP. Treatment duration was 8 weeks. RESULTS: Of the 371 patients screened, 319 were randomized and considered for efficacy and safety analysis. Both treatment groups had no significant difference in terms of demography and baseline disease characteristics. Significantly better outcomes with FDC compared to etoricoxib were observed at week 4 onwards. At week 8, both groups showed significant reduction in mean NRS score from baseline (- 4.00 ± 1.65 in FDC; - 2.92 ± 1.59 in etoricoxib) with mean NRS score being significantly less in the FDC group compared to etoricoxib group (3.26 ± 1.56 vs 4.31 ± 1.56; p < 0.0001). The FDC was more effective than etoricoxib in terms of significantly greater reduction in RDQ score (- 9.28 ± 4.48 vs - 6.78 ± 4.34; p < 0.0001) and VAS score (- 37.66 ± 18.7 vs - 28.50 ± 16.31; p < 0.0001) at week 8. The FDC was also better in terms of significantly more patients reporting their condition as 'very much better' (36.9% vs 5.0%; p < 0.0001) and clinicians reporting patient's condition as 'very much improved' (36.3% vs 5.7%; p < 0.0001). Overall, study medications were well tolerated. CONCLUSION: FDC of pregabalin and etoricoxib provided significant benefits in reducing pain and improving functional status compared with etoricoxib alone in patients with CLBP. Pregabalin prolonged release-etoricoxib FDC could be one of the treatment options for early and sustained pain relief and improvement in quality-of-life in treating CLBP as it addresses both neuropathic and nociceptive components of pain. TRIAL REGISTRATION: CTRI/2018/10/015886.

Low back pain is one of the most common causes of loss of productivity worldwide. About 60% of Indians suffer from low back pain at some point. Low back pain that persists for more than 3 months is classified as chronic low back pain which mostly includes both nociceptive and neuropathic components. Monotherapies, if prescribed, are not completely effective, as they generally only target either nociceptive or neuropathic components of pain. Multiple drugs are usually needed at multiple times a day, at higher doses for optimal effectiveness, and in most cases they have significant side effects if taken over prolonged periods and also add to the pill burden. To minimize treatment-associated adverse effects, and to increase treatment compliance, while addressing both the components of pain, we developed a fixed-dose combination of low-dose pregabalin prolonged release and etoricoxib. A phase 3 trial was designed to assess the efficacy and safety of the fixed-dose combination in comparison with etoricoxib alone in treating chronic low back pain. The combination demonstrated statistically and clinically significant improvement in patient-reported outcomes­pain, functionality and quality of life­as early as 4 weeks after starting the medication. No severe or serious adverse effects were reported. Thus, the combination of low-dose pregabalin prolonged release and etoricoxib could provide an option for optimal management of chronic low back pain. This would provide multiple benefits, such as addressing both nociceptive and neuropathic components of chronic low back pain, reducing drug-related adverse effects because of low dose, reducing pill burden and thereby increasing drug compliance.

Evaluation of scleral incisions and their effects on corneal curvature in manual small-incision cataract surgery.

Purpose: Incisions in cataract surgery can be modified in various ways in terms of size, shape, and axis to reduce or tailor astigmatism. This study was conducted to examine the effect of site (superior vs, temporal) and shape (frown vs. V-shaped, chevron) of scleral incisions for cataract surgery on corneal curvature. Methods: The prospective study was carried out on 200 consecutive patients with senile cataract and who were planned for surgery at a tertiary eye hospital in north India. The placement of the incision was decided by the steeper corneal meridian-whether superior or temporal-and then patients of these two groups were randomized for frown and V-shaped incision; in this way, four groups of 50 patients each were formed. Follow-up was done on day 1, at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. At each follow-up, post-operative keratometry with routine postoperative examination was done. The results were statistically analyzed by using student's t-test, Chi-squared test, and the Pearson correlation coefficient. Results: In all the four groups, the difference of preoperative astigmatism and surgically-induced astigmatism was statistically highly significant. The analysis of uncorrected visual acuity (UCVA) was statistically significant (P < 0.05) on postoperative day 1 and at 2, 4, and 12 postoperative weeks; it was statistically insignificant (P > 0.05) at postoperative week 8. Conclusion: Temporal incisions result in lesser postoperative surgically induced astigmatism (SIA) than superior incisions. Chevron incisions result in minimal change in corneal curvature. This effect can be utilized to tailor the postoperative astigmatism.

Interplay of Kinetic and Thermodynamic Reaction Control Explains Incorporation of Dimethylammonium Iodide into CsPbI3.

CsPbI3 is a promising material for optoelectronics owing to its thermal robustness and favorable bandgap. However, its fabrication is challenging because its photoactive phase is thermodynamically unstable at room temperature. Adding dimethylammonium (DMA) alleviates this instability and is currently understood to result in the formation of DMA x Cs1-x PbI3 perovskite solid solutions. Here, we use NMR of the 133Cs and 13C local structural probes to show that these solid solutions are not thermodynamically stable, and their synthesis under thermodynamic control leads to a segregated mixture of yellow one-dimensional DMAPbI3 phase and δ-CsPbI3. We show that mixed-cation DMA x Cs1-x PbI3 perovskite phases only form when they are kinetically trapped by rapid antisolvent-induced crystallization. We explore the energetics of DMA incorporation into CsPbI3 using first-principles calculations and molecular dynamics simulations and find that this process is energetically unfavorable. Our results provide a complete atomic-level picture of the mechanism of DMA-induced stabilization of the black perovskite phase of CsPbI3 and shed new light on this deceptively simple material.

Highly Efficient and Stable 2D Dion Jacobson/3D Perovskite Heterojunction Solar Cells.

Heterostructures involving two-dimensional/three-dimensional (2D/3D) perovskites have recently attracted increased attention due to their ability to combine the high photovoltaic performance of 3D perovskites with the increased stability of 2D perovskites. Here we report ammonium thiocyanate (NH4SCN) passivated 3D methylammonium lead triiodide (MAPbI3) perovskite active layer and deposition of 2D perovskite capping layer using xylylene diammonium iodide (XDAI) organic cation. The 2D/3D perovskite heterojunction formation is probed by using FESEM and UPS spectroscopy. The NH4SCN passivated MAPbI3 perovskite has shown 19.6% PCE compared to the 17.18% PCE of pristine MAPbI3 perovskite solar cells (PSCs). Finally, the champion 2D/3D perovskite heterojunction based solar cells have achieved the remarkable PCE of 20.74%. The increased PCE in 2D/3D PSCs is mainly attributed to the reduced defect density and suppressed nonradiative recombination losses. Moreover, the hydrophobic 2D capping layer endows the 2D/3D heterojunction perovskites with exceptional moisture, thermal and UV stability, highlighting the promise of highly stable and efficient 2D/3D PSCs.

Risk for Postmarket Black Box Warnings in FDA-Approved Monoclonal Antibodies.

OBJECTIVE: To estimate the potential risk for a future postmarket black box warning (BBW) of US Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) because of the importance for medical clinicians to understand mAb risks and benefits, including unknown future risks, especially for recently approved mAbs. METHODS: The complete dates of the study were March 16, 2020, through May 12, 2021. We searched the FDALabel database online and reviewed the scientific literature to determine current and previous FDA-approved mAbs as of March 2020. The BBWs and initial FDA-issued safety warnings were identified. The BBWs were categorized as premarket or postmarket. For mAbs with specific postmarket BBWs, previous FDA labels were evaluated to identify the presence or absence of an initial corresponding specific FDA warning. RESULTS: In March 2020, a total of 83 mAbs had FDA approval; 33 had BBWs (27 premarket and 13 postmarket BBWs). Of these 33 mAbs, 55 individual specific BBWs existed (36 premarket and 19 postmarket specific warnings). On average, the specific BBWs occurred in the postmarket period at a rate of 3.4% (19/562) per year. Most (73.7%; 14/19) specific postmarket BBWs were preceded by an FDA warning in a median time of 3.61 (interquartile range, 1.36-5.78) years. Specific postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.9% (5/562) per year. CONCLUSION: Specific postmarket BBWs occurred in FDA-approved mAbs at a rate of 3.4% per year. Specific postmarket BBWs not preceded by a specific FDA product label warning had a rate of 0.9% per year.

Thiocyanate-Passivated Diaminonaphthalene-Incorporated Dion-Jacobson Perovskite for Highly Efficient and Stable Solar Cells.

Two-dimensional (2D) metal halide perovskites have recently emerged as promising photovoltaic materials due to their superior ambient stability and rich structural diversity. However, power conversion efficiencies (PCEs) of the 2D perovskites solar cells (PSCs) still lag behind their three-dimensional (3D) counterpart, particularly due to the anisotropy in the charge carrier mobility and inhomogeneous energy landscape. A promising alternative is Dion-Jacobson (D-J) phase quasi-2D perovskite, where the bulky organic diammonium cations are introduced into inorganic frameworks to remove the weak van der Waals interactions between interlayers and to improve the open-circuit voltage (Voc). Although the D-J phase 2D perovskite shows a homogeneous energy landscape and better charge transport, their poor crystallinity and existence of higher trap states remain a major challenge for the development of high-efficiency solar cells device. To address this issue, here, we report the eclipsed D-J phase 2D perovskite using 1,5-diaminonaphthalene cation and subsequently treated the film with ammonium thiocyanate (NH4SCN) additive to further improve the film crystallinity, out-of-plane orientation, and carrier mobility. We observe that 2 mol NH4SCN surface treatment in NDA-based D-J phase perovskite leads to better film morphology and improved crystallinity, as confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Time-resolved photoluminescence (TRPL) spectroscopy and steady-state space charge limited current (SCLC) mobility measurement reveal a significant reduction of trap-assisted nonradiative recombination and improvement of carrier mobility in the thiocyanate-passivated perovskite. Consequently, the PCE of the NH4SCN-treated (NDA)(MA)3(Pb)4(I)13 perovskite device enhanced nearly 46% from 10.3 to 15.08%. We have further studied intensity-dependent J-V characteristics, which demonstrate the reduction of ideality factor, confirming the effective suppression of trap-assisted nonradiative recombination, consistent with the transient PL results. Electrochemical impedance spectroscopy (EIS) confirms the improved charge carrier transport in NH4SCN additive-treated devices. Interestingly, our additive-engineered unsealed perovskite devices retained 75% of their initial efficiency after 1000 h of continuous storage under 60% relative humidity. This study opens up the strategy for developing high-efficiency and stable 2D perovskite solar cells.

Outcomes among patients with COVID-19 and asthma: A systematic review and meta-analysis.

Background: It remains unclear if asthma is a risk factor associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19). Methods: We performed a comprehensive database search for studies published from January 1, 2019, to October 2, 2020. We included studies that evaluated outcomes among patients with COVID-19 and underlying asthma. Outcomes of interest included the need for hospitalization, length of hospitalization, intensive care unit (ICU) admission, and death. The meta-analysis was conducted by using random-effects methodology. Results: A total of 389 studies were identified through data base searches. After abstract and full-text screening, 16 observational studies with 92,275 patients were included in the analysis. Of the 16 studies, 15 were retrospective and 1 was a prospective cohort study. The average age was 39.6 years, with 48% female patients. Six of the studies included pediatric patients, and one of these studies only evaluated pediatric patients. One study only evaluated pregnant patients. Among patients with COVID-19, the presence of asthma was not associated with any significant increase in risk of hospitalization (odds ratio [OR] 1.46 [95% confidence interval {CI}, 0.29-7.28]), length of hospitalization (1.59 days [-0.55 to 3.74]), ICU admission (OR 1.65 [95% CI, 0.56-4.17]), or death (OR 0.73 [95% CI, 0.38-1.40]). The overall risk of bias of the included studies was high. Conclusion: Among the patients with COVID-19, asthma did not seem to significantly increase the risk of hospitalization, length of hospitalization, ICU admission, or death.

Azahomofullerenes as New n-Type Acceptor Materials for Efficient and Stable Inverted Planar Perovskite Solar Cells.

Fullerene derivatives with a strong electron-accepting ability play a crucial role in enhancing both the performance and stability of perovskite solar cells (PSCs). However, most of the used fullerene molecules are based on [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), which limits the device performance due to difficulties in preparing high-quality and uniform thin films. Herein, solution-processable azahomofullerene (AHF) derivatives (abbreviated as AHF-1 and AHF-2) are reported as novel and effective electron-transport layers (ETLs) in p-i-n planar PSCs. Compared to the control PCBM ETL-based PSCs, the devices based on AHFs exhibit higher photovoltaic performances, which is attributed to the enhanced charge-transport properties and improved layer morphology leading to a maximum power conversion efficiency (PCE) of 20.21% in the case of the device based on AHF-2 ETL. Besides, due to the preferable energy band alignment with the perovskite layer, reduced trap states, and suppressed charge recombination, the device with AHF-2 ETL exhibits significantly suppressed hysteresis and improved stability under both ambient and thermal conditions.

Reaching Out to the Millions: A 5 Key Messages Rapid IEC Campaign During the COVID-19 Pandemic.

The ongoing COVID-19 pandemic has necessitated providing populations with simple and relevant, actionable informational messages for them to be informed on individual and community level measures to combat the pandemic. Distilling guidance from various sources into simple actionable message themes in a short time frame should be the hallmark of any rapid health promotion campaign. We developed and disseminated actionable Information, Education and Communication (IEC) messages on prevention and control during the ongoing COVID-19 pandemic by selecting five key message themes of prevention. A modified Delphi technique was used for the development process which was peer reviewed after consensus was generated. An online training model using specifically developed YouTube videos and Zoom Meetings was utilized to train Master Trainers and the further hierarchy reaching out to 6989 Community Resource Persons at the peripheral echelons. Conservatively the population reached out has been estimated to be more than 6 million (across 1.2 million households), over a two week period in April 2020. The implementing agency has created 300 videos in around 22 languages based on the 5 Key Messages, which are available online for universal access. A rapid IEC campaign that can be developed, designed and rolled out in a short span is required for emergency situations such as the ongoing pandemic. NGOs play an important role in reaching out relevant messages to the community, filling in the gaps by virtue of their relative systemic agility.

A diagnostic codes-based algorithm improves accuracy for identification of childhood asthma in archival data sets.

OBJECTIVE: While a single but truncated ICD code (493) had been widely used for identifying asthma in asthma care and research, it significantly under-identifies asthma. We aimed to develop and validate a diagnostic codes-based algorithm for identifying asthmatics using Predetermined Asthma Criteria (PAC) as the reference. METHODS: This is a retrospective cross-sectional study which utilized two different coding systems, the Hospital Adaptation of the International Classification of Diseases, Eighth Revision (H-ICDA) and the International Classification of Diseases, Ninth Revision (ICD-9). The algorithm was developed using two population-based asthma study cohorts, and validated in a validation cohort, a random sample of the 1976-2007 Olmsted County Birth Cohort. Performance of the diagnostic codes-based algorithm for ascertaining asthma status against manual chart review for PAC (gold standard) was assessed by determining both criterion and construct validity. RESULTS: Among eligible 267 subjects of the validation cohort, 50% were male, 70% white, and the median age at last follow-up was 17 (interquartile range, 8.7-24.4) years. Asthma prevalence by PAC through manual chart review was 34%. Sensitivity and specificity of the codes-based algorithm for identifying asthma were 82% and 98% respectively. Associations of asthma-related risk factors with asthma status ascertained by the code-based algorithm were similar to those by the manual review. CONCLUSIONS: The diagnostic codes-based algorithm for identifying asthmatics improves accuracy of identification of asthma and can be a useful tool for large scale studies in a setting without automated chart review capabilities.

Temozolomide desensitization followed by metronomic dosing in patients with hypersensitivity.

PURPOSE: Temozolomide is the most effective chemotherapy for malignant glioma. Hypersensitivity requiring interruption of therapy may significantly impact patient survival. We have successfully employed temozolomide desensitization followed by metronomic dosing of temozolomide. Our purpose was to report patient characteristics and outcomes in patients with glioma (Grade 2-4) and temozolomide hypersensitivity managed by desensitization and metronomic dosing. METHODS: We performed an observational study of 15 patients at Mayo Clinic (Rochester) with a diagnosis of glioma who underwent temozolomide desensitization with subsequent metronomic dosing from May 2012 to January 2017. We calculated overall and progression-free survival using the Kaplan-Meier method, and log-rank analyses to assess for differences in survival by WHO Grade or treatment initiation. RESULTS: Median age at time of desensitization was 49.3 years (26.8-64.7 years). Median follow-up after desensitization was 35.5 months. One patient (6.7%) was unable to resume temozolomide due to recurrent allergy. The median time from first desensitization to discontinuation of metronomic temozolomide was 4.2 months (0-15.2 months). Median OS and PFS for the whole sample were 181.7 months and 44.9 months. For Grade 4, OS was 100% at 1 year, 40% at 3 years, 20% at 5 years; and PFS was 60% at 1 year, 40% at 3 years, and 20% at 5 years. CONCLUSION: Our results suggest that rapid-desensitization followed by metronomic temozolomide should be considered in patients with glioma who experience hypersensitivity. This strategy provides comparable outcomes to therapy with standard protocols, with the majority of patients able to tolerate temozolomide after desensitization with favorable disease control.

Atomic Layer Deposition of an Effective Interface Layer of TiN for Efficient and Hysteresis-Free Mesoscopic Perovskite Solar Cells.

Perovskite solar cells (PSCs) have experienced outstanding advances in power conversion efficiencies (PCEs) by employing new electron transport layers (ETLs), interface engineering, optimizing perovskite morphology, and improving charge collection efficiency. In this work, we study the role of a new ultrathin interface layer of titanium nitride (TiN) conformally deposited on a mesoporous TiO2 (mp-TiO2) scaffold using the atomic layer deposition method. Our characterization results revealed that the presence of TiN at the ETL/perovskite interface improves the charge collection as well as reduces the interface recombination. We find that the morphology (grain size) and optical properties of the perovskite film deposited on the optimized mp-TiO2/TiN ETL are improved drastically, leading to devices with a maximum PCE of 19.38% and a high open-circuit voltage (Voc) of 1.148 V with negligible hysteresis and improved environmental (∼40% RH) and thermal (80 °C) stabilities.

Revision endoscopic sinus surgery rates by chronic rhinosinusitis subtype.

BACKGROUND: Revision surgery rates following endoscopic sinus surgery (ESS) range between 7% and 50% and are influenced by many factors. This study investigates ESS outcomes for chronic rhinosinusitis (CRS) subtypes. METHODS: Retrospective review of adult CRS patients undergoing ESS with a single surgeon (2010-2015) was conducted. Outcomes were analyzed by CRS subtypes. RESULTS: ESS was performed in 424 CRS patients (CRS with nasal polyps [CRSwNP], n = 170; CRS without polyps [CRSsNP], n = 254). Most patients (309; 72.9%) could not be specifically subtyped; 115 (27.1%) were subtyped as follows: aspirin-exacerbated respiratory disease (AERD), n = 47 (11.1%); allergic fungal sinusitis (AFS), n = 39 (9.2%); immunodeficiency, n = 21 (5.0%); granulomatosis with polyangiitis (GPA), n = 5 (1.2%); and eosinophilic granulomatosis with polyangiitis (EGPA), n = 3 (0.7%). All subgroups experienced clinically meaningful reduction in postoperative 22-item Sino-Nasal Outcome Test (SNOT-22) scores. At median follow-up of 28 months (interquartile range [IQR], 10-47 months), 19 patients (4%) underwent revision ESS (CRSwNP, n = 6; CRSsNP, n = 13). Revision ESS rates were 3.5% and 5.1% for CRSwNP and CRSsNP, respectively. Revision ESS rate for subtypes were: AERD 2%; AFS 2%; immunodeficiency 14%; GPA 40%; EGPA 0%; and "all other CRS" 4% at median follow-up duration of 36, 28, 41, 37, 44, and 26 months, respectively. CONCLUSION: All CRS subtypes demonstrated clinically meaningful improvement in postoperative SNOT-22 scores following ESS. Our overall revision ESS rate was 4% (3.5% in CRSwNP). AFS, AERD, and EGPA groups demonstrated low revision rates, while immunodeficiency and GPA patients required more revision surgery. A contemporary understanding of CRSwNP subtypes facilitated surgical and medical strategies in improving outcomes for AERD, AFS, and EGPA patients. CRSsNP subtypes with immunodeficiency and GPA merit further investigation to optimize outcomes.

SNOT-22-based clusters in chronic rhinosinusitis without nasal polyposis exhibit distinct endotypic and prognostic differences.

BACKGROUND: Endotypic and prognosticating features of chronic rhinosinusitis without nasal polyposis (CRSsNP) are poorly understood. Our objectives were to use an unbiased symptom-based approach to: (1) study symptoms, clinical and endotypic features; and (2) identify features predicating outcomes from endoscopic sinus surgery (ESS). METHODS: Clinical, computed tomography (CT), histopathology, and 22-item Sino-Nasal Outcome Test (SNOT-22) data was collected on 146 adult CRSsNP patients who underwent ESS. Unsupervised network modeling of presurgical SNOT-22 scores was performed to classify symptom-based clusters. Subject characteristics and post-ESS SNOT-22 scores were compared between clusters. RESULTS: Baseline characteristics of the subject population were as follows: females, 56.2%; revision ESS status in 35%; asthma prevalence, 32.6%; median Lund-Mackay CT score, 8; and median SNOT-22 total score, 43. Network mapping and unsupervised clustering of preoperative SNOT-22 scores revealed 4 clusters: (A) severely burdened with high scores in all 4 subdomains; (B) moderately burdened with high scores in the rhinologic subdomain; (C) moderately burdened with high scores in psychological-sleep subdomains; and (D) mildly burdened. The number of previous ESS and asthma prevalence differed significantly between clusters; CT scores were similar. Asthma burden and tissue eosinophilia were greatest in cluster A (p = 0.03). All groups showed significant improvement at 3 months post-ESS (p < 0.0001). At 6 months, patients in cluster C tended to worsen. CONCLUSION: SNOT-22-based network modeling of CRSsNP patients yielded 4 clusters with distinct features. Asthma prevalence and tissue eosinophilia were highest in the cluster with highest SNOT-22 scores. All patients showed significant improvement from ESS at 3 months; those with high sleep-psychosocial symptoms tended to show worsening at 6 months.