Avoidable Benign Kidney Tumor Resections-Data from a Tertiary Care Cancer Institute.

Enhancing renal masses are conventionally treated as malignant unless proven otherwise due to the difficulty distinguishing between malignant and benign tumors based on imaging. Data from the Western registries suggests overtreatment of renal tumors with a Benign Kidney Tumor Resection Rate (BKTRR) ranging from 10 to 33%, with an increasing trend. Since robust, population-based data from India was unavailable, we sought to determine BKTRR in an apex cancer institute, which would provide insight into the rates in the community. The institutional kidney tumor database was queried for all patients aged ≥18 years with renal neoplasms between January 2000 and December 2022. Patients who underwent surgery, either radical or partial nephrectomy, with intent to cure were analyzed and the BKTRR during the study period was evaluated. A total of 330 patients underwent surgery for renal tumors presumed to be malignant. A final pathologic diagnosis of the benign tumor was made in 16 (4.8%) patients, comprising 7.2, 7.2, and 3.7% of resections with LTD ≤4, 4-7, and >7 cm, respectively. Asymptomatic benign tumors ≤7 cm comprised 3.0% of all resections, and these were potentially unnecessary surgeries. A multivariable analysis suggested that no patient or imaging characteristic could predict a final benign extirpative pathology. Our study suggests a lower rate of BKTRR compared to the published international literature but is likely to be the lower limit of that in the community. Population-based studies are required to determine the true BKTRR and the quantum of potentially unnecessary surgeries for benign kidney tumors.

New approach methodologies (NAMs) for the in vitro assessment of cleaning products for respiratory irritation: workshop report.

The use of in vitro new approach methodologies (NAMs) to assess respiratory irritation depends on several factors, including the specifics of exposure methods and cell/tissue-based test systems. This topic was examined in the context of human health risk assessment for cleaning products at a 1-day public workshop held on 2 March 2023, organized by the American Cleaning Institute® (ACI). The goals of this workshop were to (1) review in vitro NAMs for evaluation of respiratory irritation, (2) examine different perspectives on current challenges and suggested solutions, and (3) publish a manuscript of the proceedings. Targeted sessions focused on exposure methods, in vitro cell/tissue test systems, and application to human health risk assessment. The importance of characterization of assays and development of reporting standards was noted throughout the workshop. The exposure methods session emphasized that the appropriate exposure system design depends on the purpose of the assessment. This is particularly important given the many dosimetry and technical considerations affecting relevance and translation of results to human exposure scenarios. Discussion in the in vitro cell/tissue test systems session focused on the wide variety of cell systems with varying suitability for evaluating key mechanistic steps, such as molecular initiating events (MIEs) and key events (KEs) likely present in any putative respiratory irritation adverse outcome pathway (AOP). This suggests the opportunity to further develop guidance around in vitro cell/tissue test system endpoint selection, assay design, characterization and validation, and analytics that provide information about a given assay's utility. The session on applications for human health protection emphasized using mechanistic understanding to inform the choice of test systems and integration of NAMs-derived data with other data sources (e.g., physicochemical properties, exposure information, and existing in vivo data) as the basis for in vitro to in vivo extrapolation. In addition, this group noted a need to develop procedures to align NAMs-based points of departure (PODs) and uncertainty factor selection with current human health risk assessment methods, together with consideration of elements unique to in vitro data. Current approaches are described and priorities for future characterization of in vitro NAMs to assess respiratory irritation are noted.

The Fibrotic Phenotype of Human Precision-Cut Lung Slices Is Maintained after Cryopreservation.

Human precision-cut lung slices (hPCLS) prepared from fibrotic lungs recapitulate the pathophysiological hallmarks of fibrosis. These hallmark features can also be induced by treating non-fibrotic hPCLS with a fibrotic cocktail (FC). As a result, the fibrotic and fibrosis-induced hPCLS are rapidly emerging as preferred models for disease modeling and drug discovery. However, current hPCLS models are limited by tissue viability in culture, as they are usually only viable for one week after harvesting. Here, we demonstrate that the fibrotic hPCLS can be cryopreserved, stored for months, and then thawed on demand without loss of hPCLS viability or protein content for 14 days post-thawing. Cryopreservation also preserves the pro-fibrotic potential of non-fibrotic hPCLS. Specifically, when we treated the thawed non-fibrotic hPCLS with an FC, we observed significant pro-fibrotic cytokine secretion and elevated tissue stiffness. These pro-fibrotic changes were inhibited by the small-molecule tyrosine kinase inhibitor, Nintedanib. Taken together, our work indicates that a feasible solution to prolong the pre-clinical utility of fibrotic and fibrosis-induced hPCLS is cryopreservation. We anticipate that cryopreserved hPCLS will serve as an advantageous predictive model for the evaluation of pro-fibrotic pathways during acute and chronic toxicity testing.

Impact of Balloon-Expandable TAVR Valve Deformation and Calcium Distribution on Outcomes in Bicuspid Aortic Valve.

BACKGROUND: Research on the role of transcatheter heart valve (THV) deformation and calcium distribution in patients with bicuspid aortic valves (BAVs) undergoing transcatheter aortic valve replacement (TAVR) remains limited. OBJECTIVES: The aim of this study was to evaluate the impact of THV deformation on clinical outcomes in individuals with BAVs undergoing TAVR and the influence of calcium on these outcomes. METHODS: In total, 229 consecutive patients with BAVs who underwent TAVR with balloon-expandable valves and had computed tomography (CT) performed 30 days post-TAVR were analyzed. Patients were stratified into 3 groups: group 1 (n = 125), with no THV underexpansion or eccentricity; group 2 (n = 69), with underexpansion or eccentricity; and group 3 (n = 35), with both. Calcium distribution was assessed using CT, and its associations with clinical outcomes, including all-cause mortality at 3 years and leaflet thrombosis at 30 days, were determined. A subgroup analysis of patients with type 1 BAVs was conducted. RESULTS: Group 3 exhibited higher rates of all-cause mortality than the other groups, along with the highest risk for hypoattenuated leaflet thickening at 30 days. Multivariate analysis identified annular and left ventricular outflow tract calcification as independent predictors of all-cause mortality and hypoattenuated leaflet thickening. In patients with type 1 BAVs, excessive calcification at the raphe and opposite leaflet were associated with all-cause mortality at 3 years. CONCLUSIONS: THV deformation post-TAVR was significantly linked to all-cause mortality in patients with BAVs. Annular and left ventricular outflow tract calcification correlated with increased risks for all-cause mortality and leaflet thrombosis. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).

Use of arterial transposition for vascular reconstruction within contaminated or infected abdominal fields.

Intra-abdominal arterial reconstructions in the setting of reoperative, contaminated, or frankly infected fields can be a challenging undertaking for even the most experienced vascular surgeons. Open surgical arterial transpositions have been less commonly performed than other methods of reconstruction in the current era of vascular surgery despite many historical reports of successful outcomes. Autologous artery transpositions represent a viable option in the case of an infected or a contaminated operative field. We have described the cases of three patients treated at our institution who had required intra-abdominal revascularization in a contaminated or frankly infected surgical field. All three patients were successfully treated using open native visceral artery transposition procedures. These cases presented multiple challenges secondary to the ongoing infections, infected operative field, and, sometimes, a history of multiple vascular bypasses involving the aorta and visceral arteries. In such circumstances, we have demonstrated the effectiveness of native visceral arterial transposition as a feasible technique.

Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. METHODS: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. RESULTS: Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). CONCLUSION: In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.

Visual Cortical Thickness Increases with Prolonged Artificial Vision Restoration.

The Argus II retinal prosthesis restores visual perception to late blind patients. It has been shown that structural changes occur in the brain due to late-onset blindness, including cortical thinning in visual regions of the brain. Following vision restoration, it is not yet known whether these visual regions are reinvigorated and regain a normal cortical thickness or retain the diminished thickness from blindness. We evaluated the cortical thicknesses of ten Argus II Retinal Prostheses patients, ten blind patients, and thirteen sighted participants. The Argus II patients on average had a thicker left Cuneus Cortex and Lateral Occipital Cortex relative to the blind patients. The duration of the Argus II use (time since implant in active users) significantly partially correlated with thicker visual cortical regions in the left hemisphere. Furthermore, in the two case studies (scanned before and after implantation), the patient with longer device use (44.5 months) had an increase in the cortical thickness of visual regions, whereas the shorter-using patient did not (6.5 months). Finally, a third case, scanned at three time points post-implantation, showed an increase in cortical thickness in the Lateral Occipital Cortex between 43.5 and 57 months, which was maintained even after 3 years of disuse (106 months). Overall, the Argus II patients' cortical thickness was on average significantly rejuvenated in two higher visual regions and, patients using the implant for a longer duration had thicker visual regions. This research raises the possibility of structural plasticity reversing visual cortical atrophy in late-blind patients with prolonged vision restoration.

A Retrospective Study to Evaluate Discrepancies in Urban Versus Rural Mortality Due to Brain Cancer in the United States.

INTRODUCTION: The study aims to examine the disparities in mortality rates attributed to brain cancer between urban and rural areas over a 22-year period, totaling 315,538 deaths. This investigation serves as a crucial step in identifying areas within healthcare that require improvement. By pinpointing the variations in mortality rates between urban and rural settings, healthcare authorities can strategically implement necessary interventions. METHODOLOGY: A retrospective study was conducted by analyzing the death certificate available on the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2020 to evaluate the mortality rate trends of brain cancer ( International Classification of Diseases (ICD)-10 C71.0-71.9).The data was grouped based on rural and urban death rates according to the 2013 urbanization classification and the variables that were used were age, gender and race. Data was analyzed using Microsoft Excel and R Studio 4.3.1. Significant associations between demographic variables and mortality rates were identified via Binomial tests. RESULTS: From 1999 to 2020, urban areas recorded 259,402 deaths attributed to brain cancer, compared to 56,136 deaths in rural areas, indicating a higher mortality rate in urban settings. The mortality rate in both rural and urban areas exhibited an upward trend, except for a slight drop in 2010. The mortality rates were significantly higher in rural areas compared to urban areas for age groups 55-64 years and 65-74 years, males and caucasians. CONCLUSIONS: Our research underscores the differences in death rates from brain cancer between urban and rural areas, specifically among individuals aged 55-64 and 65-74, males and those of caucasian ethnicity. Future research must adopt a multifaceted approach, integrating more recent datasets and embracing a finer granularity of individual-level information. Moreover, there is a pressing need to explore the interplay of various factors such as access to healthcare, treatment modalities, genetic predispositions, and socioeconomic determinants on mortality outcomes.

Use of cervical traction for managing neck pain: A cross-sectional survey of physiotherapists in India.

BACKGROUND: Neck pain remains the fourth leading cause of disability and work loss, and a multimodal treatment approach is effective in reducing neck pain and disability. PURPOSE: The purpose of this study is to examine the use of cervical traction for managing neck pain by Physiotherapists in India, including how and when the traction is used, the modes and parameters of traction, any additional interventions given with traction, and the influence of professional demographic characteristics in decision making in traction usage. STUDY DESIGN: A cross-sectional survey. METHODOLOGY: A random sample of approximately 2500 musculoskeletal physiotherapists was surveyed, and the data was presented in a descriptive form. Chi-square analyses were used to identify the association between responders' qualifications and traction usage. RESULTS: From the total physiotherapist approached 18.52% (n = 463) responses were obtained, and 62% (n = 287) respondents reported that they would use traction in their clinical practice. Out of 92.3% of responders indicated using traction for radiculopathy, 78.7% of respondents used traction for patients with neck pain without radiculopathy. It is used as a combination therapy by 58.8% for radiculopathy and 52.2% for stiffness. There was no association between the responder's qualification and traction usage (χ2 = 0.707, p = 0.40). Traction is used in combination with other physiotherapeutic techniques. CONCLUSION: Traction use was consistent with the proposed criteria identifying patients likely to benefit. However, disregarding current guidelines, physiotherapists also use traction for non-radicular neck pain. Various traction delivery modes and parameters were used within a comprehensive plan of care incorporating multiple interventions.

Effects of Serum Potassium on Mortality in Patients With ST-Elevation Myocardial Infarction.

INTRODUCTION: Disturbances in potassium levels can induce ventricular arrhythmias and heighten mortality in patients with ST-elevation myocardial infarction (STEMI). This study evaluates the influence of sK levels on seven-day mortality and incidence of ventricular arrhythmias in STEMI patients to further improve clinical guidelines and outcomes. METHODS: This retrospective, propensity-matched study analyzed approximately 250,000 acute STEMI patients from 55 major academic medical centers/healthcare organizations (HCOs) in the US Collaborative Network of the TriNetX database. The sK levels recorded on the day of STEMI diagnosis were categorized into four cohorts: sK ≤ 3.4 (hypokalemia), 3.5 ≤ sK ≤ 4.5 (normal-control), 4.6 ≤ sK ≤ 5.0 (high-normal), and sK ≥ 5.1 (hyperkalemia). Patient cohorts were propensity-matched using linear and logistic regression for demographics. Outcomes of seven-day mortality, ventricular tachycardia (VT), and ventricular fibrillation (VF) were compared between these cohorts and the control group. RESULTS: The analysis showed hypokalemia was linked to significantly higher seven-day mortality (7.2% vs. 4.3%; RR 1.69; p<0.001), and increased rates of VT and VF. Similarly, hyperkalemia was associated with elevated mortality (12.7% vs. 4.6%; RR 2.76; p<0.001), VT, and VF rates. High-normal sK levels showed increased mortality (7.4% vs. 4.7%; RR 1.58; p<0.001), but unchanged VT or VF rates compared to the normal sK group. CONCLUSION: This comprehensive study highlights the correlation of sK levels with death in STEMI patients, revealing a nearly doubled risk of mortality with hypokalemia and almost triples with hyperkalemia. More notably, the mortality for STEMIs is higher for high-normal vs normal sK values. Additionally, hypokalemia and hyperkalemia were found to significantly elevate VT and VF risks.

Two-Year Clinical Outcomes of Staged Transcatheter Mitral Edge-to-Edge Repair After Transcatheter Aortic Valve Replacement.

Residual significant mitral regurgitation (MR) can increase the risk of adverse events after transcatheter aortic valve replacement (TAVR). The clinical benefits of staged transcatheter edge-to-edge repair (TEER) after TAVR remain underexplored. This study aimed to investigate the clinical outcomes of staged TEER for residual significant MR after TAVR. This observational study included 314 consecutive patients with chronic residual grade 3+ or 4+ MR at the 30-day follow-up after TAVR, with 104 patients (33.1%) treated with staged TEER (TEER group) and 210 (66.9%) with medical therapy alone. The primary composite outcomes were all-cause mortality and heart failure hospitalization at 2 years. Additional analysis, including changes in MR grade and the New York Association functional classification, and subgroup outcome comparisons based on MR etiology were also conducted. In our study, the rate of primary composite outcome was lower in the TEER group than in the medical therapy alone group (33.7% vs 48.1%, p = 0.015). Significant improvement in MR grade and New York Association class was observed in the TEER group after 2 years. The subgroup analysis demonstrated that in patients with degenerative MR, a lower incidence of composite outcome and heart failure hospitalization was observed in the TEER group (hazard ratio 0.35, 95% confidence interval 0.23 to 0.53, p <0.001). In conclusion, staged TEER after TAVR was associated with reduced MR and improved clinical outcomes. The clinical significance of MR after TAVR should be carefully evaluated, and TEER should be considered for patients with significant residual MR, particularly, those with degenerative MR.

Elevated cardiovascular risk and acute events in hospitalized colon cancer survivors: A decade-apart study of two nationwide cohorts.

BACKGROUND: Over the years, strides in colon cancer detection and treatment have boosted survival rates; yet, post-colon cancer survival entails cardiovascular disease (CVD) risks. Research on CVD risks and acute cardiovascular events in colorectal cancer survivors has been limited. AIM: To compare the CVD risk and adverse cardiovascular outcomes in current colon cancer survivors compared to a decade ago. METHODS: We analyzed 2007 and 2017 hospitalization data from the National Inpatient Sample, studying two colon cancer survivor groups for CVD risk factors, mortality rates, and major adverse events like pulmonary embolism, arrhythmia, cardiac arrest, and stroke, adjusting for confounders via multivariable regression analysis. RESULTS: Of total colon cancer survivors hospitalized in 2007 (n = 177542) and 2017 (n = 178325), the 2017 cohort often consisted of younger (76 vs 77 years), male, African-American, and Hispanic patients admitted non-electively vs the 2007 cohort. Furthermore, the 2017 cohort had higher rates of smoking, alcohol abuse, drug abuse, coagulopathy, liver disease, weight loss, and renal failure. Patients in the 2017 cohort also had higher rates of cardiovascular comorbidities, including hypertension, hyperlipidemia, diabetes, obesity, peripheral vascular disease, congestive heart failure, and at least one traditional CVD (P < 0.001) vs the 2007 cohort. On adjusted multivariable analysis, the 2017 cohort had a significantly higher risk of pulmonary embolism (PE) (OR: 1.47, 95%CI: 1.37-1.48), arrhythmia (OR: 1.41, 95%CI: 1.38-1.43), atrial fibrillation/flutter (OR: 1.61, 95%CI: 1.58-1.64), cardiac arrest including ventricular tachyarrhythmia (OR: 1.63, 95%CI: 1.46-1.82), and stroke (OR: 1.28, 95%CI: 1.22-1.34) with comparable all-cause mortality and fewer routine discharges (48.4% vs 55.0%) (P < 0.001) vs the 2007 cohort. CONCLUSION: Colon cancer survivors hospitalized 10 years apart in the United States showed an increased CVD risk with an increased risk of acute cardiovascular events (stroke 28%, PE 47%, arrhythmia 41%, and cardiac arrest 63%). It is vital to regularly screen colon cancer survivors with concomitant CVD risk factors to curtail long-term cardiovascular complications.

Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all [100%; 95% confidence interval (CI) 94%-100.0%, P < .001] patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 [98.3%; 95% CI (91.1%-100%)] patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1%-99.0%). Within 90 days, freedom from mortality was 95% [95% CI (86.1%-99.0%)], without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favourable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

TAVR-in-TAVR with a balloon-expandable valve for paravalvular leak.

Introduction: Paravalvular leak (PVL) is a severe complication of transcatheter aortic valve replacement (TAVR) that can lead to poor outcomes. TAVR-in-TAVR is a promising treatment for PVL; however, reports on its safety or efficacy are limited. In this study, we aimed to investigate the clinical outcomes of TAVR-in-TAVR using balloon-expandable prostheses for PVLs after TAVR. Methods: We retrospectively analyzed data from patients who underwent TAVR-in-TAVR using balloon-expandable Sapien prostheses for PVL after an initial TAVR at our institution. The procedural success, in-hospital complications, all-cause mortality, and echocardiographic data for up to 2 years post-surgery were evaluated. Results: In total, 31 patients with a mean age of 81.1 ± 7.9 years and mean Society of Thoracic Surgeons score of 8.8 ± 5.4% were identified. The procedural success rate of TAVR-in-TAVR was 96.8% (30/31). No in-hospital deaths, cardiac tamponade, or conversion to sternotomy occurred. Re-intervention was performed in only one patient (3.2%) during hospitalization. The all-cause mortality rates at 30 days and 2 years were 0% and 16.1%, respectively. A significant reduction in the PVL rate was observed at 30 days compared with that at baseline (p < 0.01). Discussion: Our findings suggest that TAVR-in-TAVR using balloon-expandable prostheses is safe and effective for PVL after TAVR with low complication rates and acceptable long-term outcomes. Further studies with larger sample sizes are needed to confirm our findings.

Prognostic value of left ventricular global longitudinal strain in transcatheter edge-to-edge repair for chronic primary mitral regurgitation.

AIMS: Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. METHODS AND RESULTS: We conducted a single-centre, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9% to -16%, -15.9% to -12%, >-12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability-all along the first year after intervention. Subjects with worse (i.e. less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9% vs. 6.3%, Log-Rank P = 0.005, HR 1.75, 95% CI 1.08-4.74, P = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1% vs. 11.5%, Log-Rank P = 0.037, HR 1.68, 95% CI 1.02-5.46, P = 0.047). No association was demonstrated between baseline LVGLS and other endpoints. Upon exploratory analysis, 1-month post-procedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value-but not the presence/extent of deterioration-conferred heightened risk for the primary outcome. CONCLUSION: TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favourable post-procedural course, presumably reflecting a higher-risk patient profile.

Management of Pediatric Patients With Spontaneous Pneumomediastinum: A Retrospective Chart Review.

PURPOSE: Given the paucity of data on pediatric spontaneous pneumomediastinum (SPM), management is largely informed by extrapolation from adult studies or personal clinical experience, resulting in significant heterogeneity. The purpose of this study was to describe how pediatric patients with SPM are clinically managed at our institution and propose a treatment algorithm. METHODS: Retrospective chart review of pediatric patients with SPM from April 2002 to December 2021 at a single Canadian tertiary care center. Data on medical history, presentation characteristics, clinical management, and complications were gathered. Descriptive and inferential statistics were used to analyze data. RESULTS: We identified 63 patients for inclusion, median age was 15 years. Twenty-nine patients were transferred from another facility. Most common presenting symptoms were chest pain (72.3%), shortness of breath (44.6%), and subcutaneous emphysema (21.5%). Initial workup included chest x-ray (93.6%), CT scan (20.6%), and upper GI series (7.9%). There was no difference in the number of initial tests between admitted and discharged patients (p = 0.10). Of admitted patients (n = 35), 31.4% had primary SPM (no underlying comorbidity/inciting event) and 68.8% were secondary SPM (underlying comorbidity/inciting event). No patients with primary SPM developed complications or recurrences. In contrast, 16.7% of those with secondary SPM developed complications and 54.2% had at least one additional intervention after admission. DISCUSSION: There is significant variability in diagnostic investigation and treatment of pediatric SPM at our center. Amongst primary SPM, additional tests did not change complication rate or recurrence, including those transferred from another facility. An expeditious treatment algorithm is warranted. TYPE OF STUDY: Retrospective Cohort Study. LEVEL OF EVIDENCE: III.

Mitral Transcatheter Edge-to-Edge Repair in Nonagenarians.

BACKGROUND: There are scarce data regarding mitral transcatheter edge-to-edge repair (TEER) in individuals aged 90 years and above. We aimed to evaluate patient characteristics, procedural aspects, and outcomes in this rapidly growing group. METHODS: We retrospectively studied a single-centre database of 967 isolated, first-time interventions, 103 (10.7%) of which were performed in nonagenarians. Outcomes included all-cause mortality, heart failure (HF) hospitalizations, and the persistence of significant mitral regurgitation (MR) or New York Heart Association functional class III/IV during the first postprocedural year. Analyses were repeated on a 204-patient, propensity score-matched subcohort, controlling for MitraScore elements, sex, race, MR etiology, functional status, atrial fibrillation/flutter, and procedural urgency. RESULTS: Compared with subjects below 90 years of age, nonagenarians were more likely to be white women of higher socioeconomic status; had a higher interventional risk, driven mainly by age and chronic kidney disease; presented more often with primary MR (71.8 vs 39.1%, P < 0.001); and exhibited less advanced biochemical/echocardiographic indices of cardiac remodelling. Further, their procedures were more commonly nonurgent and used fewer devices. A similarly high (> 97%) technical success rate was achieved in the 2 study groups. Likewise, no intergroup differences were observed in the rates or cumulative incidences of any of the explored endpoints, and neither of the outcomes' risks was associated with age 90 and above. Comparable outcomes were also noted in the propensity score-matched subgroups. CONCLUSIONS: In our experience, mitral TEER was equally feasible, safe, and efficacious in patients below and above 90 years of age.

Implications of Mitral Annular Calcification on Outcomes Following Mitral Transcatheter Edge-to-Edge Repair.

BACKGROUND: Limited data exist regarding the impact of mitral annular calcification (MAC) on outcomes of transcatheter edge-to-edge repair for mitral regurgitation (MR). METHODS: We retrospectively analyzed 968 individuals (median age, 79 [interquartile range, 70-86] years; 60.0% males; 51.8% with functional MR) who underwent an isolated, first-time intervention. Stratified by MAC extent per baseline transthoracic echocardiogram, the cohort was assessed for residual MR, functional status, all-cause mortality, heart failure hospitalizations, and mitral reinterventions post-procedure. RESULTS: Patients with above-mild MAC (n=101; 10.4%) were older and more likely to be female, exhibited a greater burden of comorbidities, and presented more often with severe, primary MR. Procedural aspects and technical success rate were unaffected by MAC magnitude, as was the significant improvement from baseline in MR severity and functional status along the first postprocedural year. However, the persistence of above-moderate MR or functional classes III and IV at 1 year and the cumulative incidence of reinterventions at 2 years were overall more pronounced within the above-mild MAC group (significant MR or functional impairment, 44.7% versus 29.9%, P=0.060; reinterventions, 11.9% versus 6.2%, P=0.033; log-rank P=0.035). No link was demonstrated between MAC degree and the cumulative incidence or risk of mortality and mortality or heart failure hospitalizations. Differences in outcomes frequencies were mostly confined to the primary MR subgroup, in which patients with above-mild MAC also experienced earlier, more frequent 2-year heart failure hospitalizations (20.8% versus 9.6%; P=0.016; log-rank P=0.020). CONCLUSIONS: Mitral transcatheter edge-to-edge repair in patients with and without above-mild MAC is equally feasible and safe; however, its postprocedural course is less favorable among those with primary MR.

A Comparative Preclinical Evaluation of a Novel Difluprednate 0.04% BID Ophthalmic Solution and Marketed 0.05% QID Ophthalmic Emulsion.

Purpose: The purpose of this study was to compare the efficacy, and ocular pharmacokinetics of a new 0.04% w/v bis in die means twice a day (BID) ophthalmic solution and marketed 0.05% w/v quater in die means four times a day (QID) ophthalmic emulsion of difluprednate in New Zealand white (NZW) rabbits. Methods: The preclinical proof of concept was established in paracentesis-induced acute inflammation, endotoxin-induced acute uveitis, and bovine serum albumin-induced chronic uveitis in NZW rabbit animal models. A comparison of clinical score, total cell count, and total protein was performed to determine efficacy. An ocular pharmacokinetic study was conducted to study the influence of the vehicle on the ocular absorption of the drug. Results: In both uveitis models, the new solution formulation and marketed emulsion formulation inhibited total clinical score, total cell count, PGE2, and total protein significantly more than the placebo and lipopolysaccharide (disease control) groups and were comparable. In an ocular pharmacokinetic study, the Cmax and AUC0-t of difluoroprednisolone 17-butyrate in humor were ∼2-fold higher after 14 days' instillation of new solution formulation (0.04% w/v, BID) compared with 14 days' instillation of marketed emulsion (0.05% w/v, QID). Conclusions: The study demonstrated that the efficacy of the solution formulation at a lower dose and reduced dosing regimen were comparable to that of the emulsion formulation. The reduction in strength and regimen may result in improved patient adherence and outcomes.