Double Reinforcing Strategy with Perpendicular Plate of Ethmoid in Asian Secondary Unilateral Cleft Rhinoplasty: A Finite Element Analysis.

BACKGROUND: Deviation and asymmetry relapse after secondary unilateral cleft rhinoplasty with septal extension graft is a common yet serious problem especially among Asian patients. Therefore, finding an effective approach to reduce deformity relapse remains a great challenge to plastic surgeons. METHODS: In this study, authors established finite element models to simulate different nasal cartilage-corrected options and different reinforcing strategies in secondary unilateral cleft rhinoplasty. A load of 0.01N was given to the nasal tip to simulate the soft tissue pressure, while two loads of 0.5N were separately given to the anterior and posterior part of the septal extension graft to simulate the rhinoplasty condition. Maximum deformations were evaluated to make stability judgments. RESULTS: The maximum deformation of different cartilage correction models in ascending order was: UCL deformity with septum correction, normal nasal cartilage, UCL nasal deformity, and UCL nasal deformity with lower lateral cartilage correction. When applied L-strut reinforcement graft was harvested from the perpendicular plate of the ethmoid bone, the maximum deformation of the models decreased significantly, and strong fixation of the septum could further enhance this decreasing effect. CONCLUSIONS: Correcting the septum and lower lateral cartilage together could improve the structural stability and symmetry in secondary unilateral cleft rhinoplasty. To keep the corrected septum stable and thus reduce deformity relapse, reinforcing the L-strut with perpendicular plate of ethmoid graft while strongly anchoring the septal cartilage to the anterior nasal spine was proved to be effective in both finite element analysis and clinical observation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effective extension and access to education drive optimal adoption of climate-smart agriculture interventions in affected tidal floodplains: A case study.

Developing countries with predominantly agricultural economies are particularly vulnerable to short-term climate variability and long-term climate change adversities. This provides the context for adopting climate-smart agricultural (CSA) practices to ensure consistent agricultural product supply and food security. Although concepts of CSA tools and strategies are well-established, their adoption trends in developing regions are still undesirable, with little to no empirical understanding of factors contributing to these trends. The current research aims to address this gap of knowledge by assessing the nature of climate change impacts, adaptation strategies, and socio-economic characteristics of the farmers influencing the adoption of CSA techniques in a rural cohort in Southwestern Bangladesh. Systematically designed interview schedules revealed that the most common and devastating consequences of climate change in the study area were increased infestation of pests and diseases. Other overlooked hazards including water-logging, cyclones and cold waves, are posing new threats to regional agriculture by changing conventional patterns. Contrary to the status quo, many CSA technologies, especially indigenous approaches, are widely and effectively adopted by farmers in the studied area to cope with climate change. These adoption tendencies and innovations in CSA were found to be significantly driven by factors such as extension and training programs, education of farmers, and dependence on on-farming income. The findings of the current study provide a preliminary analysis of the attitude, knowledge and trends of CSA technology adoption by farmers in a less-saline floodplain niche of a predominantly salinity-impacted coastal region. The study acts as a model for future relevant investigations and implementations for stakeholders with supply of inputs, technologies and expertise in finding sustainable solutions and appropriate extension for communities around the world confronted with similar challenges.

Use of patent term extensions to restore regulatory time for medical devices in the United States.

BACKGROUND: Medical devices can seek patent term extensions (PTEs), which extend market exclusivity to compensate for delays related to clinical trials and regulatory review. Pharmaceutical companies commonly use PTEs, but their use by medical device companies has not been clear. RESEARCH DESIGN AND METHODS: We examined the use of PTEs by medical device companies between 1984 and 2024 using a database published in the Federal Register and a list published by the Patent and Trademark Office. RESULTS: Only 178 medical device submissions were linked to a PTE application. They were mostly concentrated in 116 product codes associated with 15 medical specialties; nearly half were associated with cardiovascular devices. Numbers increased significantly in the past decade. Successful applications restored 987 days on average. CONCLUSIONS: The patent restoration opportunity appears underutilized. It is unclear whether some companies do not recognize the opportunity it promises, or whether it does not meet their needs. Different business features and marketing strategies in device versus pharmaceutical industries may decrease the usefulness of the PTE program for these types of medical products. However, the finding that a small subset of manufacturers operating in competitive markets adopted patent extension strategies more commonly suggests a significant competitive advantage when competition increases.

Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety.

Rationale & Objective: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years. Study Design: Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years. Setting & Participants: Patients with FSGS, excluding secondary FSGS. Intervention: Sparsentan (200, 400, and 800 mg/d). Outcomes: Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years. Results: 109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56; P = 0.03) and in the first 2 years (-1.69 vs -6.46; P = 0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths. Limitations: The open-label extension does not include a comparison group. Conclusions: Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.

There is substantial unmet clinical need for safe and effective treatments for focal segmental glomerulosclerosis (FSGS), a kidney lesion with varied causes. Sparsentan is being studied for treatment of FSGS and targets 2 important pathways (endothelin-1 and angiotensin II) that lead to the loss of kidney function. In the 8-week randomized, double-blind DUET study in patients with FSGS, sparsentan reduced the amount of protein in the urine better than irbesartan (a blood pressure medicine often used to treat FSGS). We examined long-term treatment with sparsentan over >4 years in the DUET open-label extension. We found sustained proteinuria reduction in patients who continued treatment with sparsentan and a consistent safety profile with no new or unexpected adverse effects.

Lymph node metastasis burden identifies head and neck squamous cell carcinoma patients benefiting from adjuvant chemoradiation: A propensity score-matching.

INTRODUCTION: To examine the influence of adjuvant chemoradiation therapy (CRT) on survival, stratified by varying numbers and level involved of metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients who underwent surgery for metastatic, negative margin HNSCC without extranodal extension were retrospectively enrolled and divided into two groups based on adjuvant therapy received: radiotherapy (RT) and CRT. The impact of RT versus CRT, stratified by the number of positive lymph nodes and the level involved, on Disease-Free Survival (DFS) and Overall Survival (OS) was analyzed. RESULTS: Following propensity score matching, a total of 580 patients were included. The burden and level of lymph node metastasis were independent predictors of poorer survival. Among patients with no more than two positive lymph nodes or involvement of levels I-III, the addition of chemotherapy to RT did not demonstrate a significant improvement in prognosis. However, in patients with three or more positive lymph nodes, CRT showed improved DFS and OS compared to RT. In patients with involvement of levels IV-V, the addition of chemotherapy to RT resulted in a significant 24 % reduction in the risk of recurrence and a 20 % decrease in the risk of death. CONCLUSION: Incorporation of adjuvant chemoradiation can lead to a favorable prognosis in patients with metastatic HNSCC. This impact was notable in cases where there were three or more positive lymph nodes or involvement of levels IV-V.

Submucosal Trans-Septal Suturing Technique After a Septal Extension Graft with Porous High-Density Polyethylene: A Technical Report.

BACKGROUND: Porous high-density polyethylene (pHDPE) is an alternative material for a septal extension graft (SEG) in oriental rhinoplasty when autologous cartilage is limited. Although nasal packing (NP) and trans-septal suturing (TSS) techniques are routine procedures to obviate the dead space after septoplasty, they are associated with certain discomforts and complications. OBJECTIVE: To investigate the application of a submucosal trans-septal suturing (STSS) technique after SEG with pHDPE. METHODS: A prospective study was conducted on 60 female participants who underwent SEG with pHDPE. The participants were randomly divided into the NP group and STSS group. The extra surgical duration of NP and STSS, pain, nasal obstruction, and sleeping disturbance as well as postoperative complications were recorded and compared between groups. RESULTS: No significant difference was found between group NP and group STSS in terms of mean age. The mean extra surgical duration of group STSS was significantly longer than group NP. There were significant higher pains of group NP at 24 hours and 48 hours postoperatively, compared with group STSS. The NP group also experienced significantly more nasal obstruction and sleep disturbance within 48h postoperatively compared to the STSS group. There was one infection in each group, minor bleeding in two NP patients, and one STSS patient. There was no major bleeding, hematoma, graft exposure, or septal perforation in both groups. CONCLUSION: Although STSS needs a longer extra surgical duration than NP, it significantly improves the patient's postoperative comfort with a faster return to normal respiration compared to NP. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Primary spinal oligodendroglioma with intracranial extension: a case report.

Introduction: Primary spinal cord oligodendrogliomas (PSO) are sporadic tumors that arise from oligodendrocytes in the central nervous system (CNS). They can affect adults and children and make up about 2% of all intramedullary (IM) spinal tumors. Here, the authors present the second case in the literature of a primary spinal oligodendroglioma with intracranial extension. Presentation: A 28-year-old right-handed female presented to our emergency room severely malaised with left-sided hemiparesis, numbness, tingling, and urinary retention with positive Babinski and negative Hoffmann. MRI showed a widespread heterogeneous mass extending from the medulla to C7 with syringomyelia inferior to the mass. The mass was removed surgically, and her neurological condition improved rapidly. The gross, pathological exams, and immunohistochemistry confirmed the diagnosis of oligodendroglioma. Discussion: Up until 2017, there have been 60 documented cases of PSO in the literature and we have found two more cases in our search between 2017 and 2023. Also, there has been only one case recorded with an intracranial extension, making our case the 63rd PSO case and the second one with cranial extension. Conclusion: The golden standard for imaging is MRI. Surgical excision is the main treatment in the literature. Single-stage laminectomy showed promising results and surgical resection was the critical intervention to which the patient responded. This matches what was stated in the literature that surgery is the primary mode of treatment in PSO patients.

Retrosternal thyrothymic remnant affects completeness of thyroidectomy: A case report.

INTRODUCTION AND IMPORTANCE: The majority of surgical thyroid disorders are treated by thyroidectomy (total or hemithyroidectomy). Anatomical variants of embryologic origin may threaten the effectiveness of thyroid surgery and complete removal of thyroid tissue. CASE PRESENTATION: A female patient who underwent a total thyroidectomy, postoperatively had normal serum thyroid-stimulating hormone (TSH) levels without hormone replacement. Serum TSH and thyroglobulin levels were within normal range. A thyroid nuclear scan and chest magnetic resonance imaging (MRI) indicated a large retrosternal thyroid remnant. Clinical discussion: Separated thyroid remnant in the thyrothymic tract, forgotten during primary surgery, was the source of hormone production. Total thyroidectomy was not achieved due to embryologic remnant, and complete resection of thyroid tissue was affected by separated retrosternal thyrothymic rest. CONCLUSION: Surgeon awareness of anatomic variants of embryological origin undoubtedly improves thyroid surgery outcomes. Beside the anatomically based approach, total thyroidectomy could be achieved by an embryologically based approach.

Proximity extension assay in cerebrospinal fluid identifies neurofilament light chain as biomarker of neurodegeneration in sporadic cerebral amyloid angiopathy.

BACKGROUND: Sporadic cerebral amyloid angiopathy (sCAA) is a disease characterised by the progressive deposition of the amyloid beta (Aß) in the cerebral vasculature, capable of causing a variety of symptoms, from (mild) cognitive impairment, to micro- and major haemorrhagic lesions. Modern diagnosis of sCAA relies on radiological detection of late-stage hallmarks of disease, complicating early diagnosis and potential interventions in disease progression. Our goal in this study was to identify and validate novel biomarkers for sCAA. METHODS: We performed a proximity extension assay (PEA) on cerebrospinal fluid (CSF) samples of sCAA/control participants (n = 34/51). Additionally, we attempted to validate the top candidate biomarker in CSF and serum samples (n = 38/26) in a largely overlapping validation cohort, through analysis with a targeted immunoassay. RESULTS: Thirteen proteins were differentially expressed through PEA, with top candidate NFL significantly increased in CSF of sCAA patients (p < 0.0001). Validation analyses using immunoassays revealed increased CSF and serum NFL levels in sCAA patients (both p < 0.0001) with good discrimination between sCAA and controls (AUC: 0.85; AUC: 0.79 respectively). Additionally, the CSF: serum NFL ratio was significantly elevated in sCAA (p = 0.002). DISCUSSION: Large-scale targeted proteomics screening of CSF of sCAA patients and controls identified thirteen biomarker candidates for sCAA. Orthogonal validation of NFL identified NFL in CSF and serum as biomarker, capable of differentiating between sCAA patients and controls.

Effects of clamshell exercises in terminal extension lag after ACL reconstruction.

BACKGROUND: Terminal extension lag (TEL) is common following anterior cruciate ligament reconstruction (ACLR). Clamshell exercises have been suggested as a potential intervention to address TEL, but limited research has been conducted in this area. OBJECTIVE: This study aimed to determine the effects of Clamshell exercises in terminal extension lag after anterior cruciate ligament reconstruction. METHODS: This randomized controlled trial included 40 participants with a history of ACLR between 1 and 3 years prior. Participants were randomly assigned to either the experimental group (Group A) or the control group (Group B). Group A received conventional exercises along with isolated hip strengthening rehabilitation, while Group B received conventional exercises without specific hip strengthening. The primary outcomes were pain levels (Numeric Pain Rating Scale), knee function (International Knee Documentation Committee scores, (IKDC)), range of motions (goniometer) and strength (sphygmomanometer). RESULTS: In between the group comparison shows that all outcome measures (NPRS, IKDC, Goniometer, Sphygmomanometer) show significant results (p < 0.05). Within-group comparisons (paired sample t-test) show that there was a significant difference (p < 0.05) in all outcome measures of both groups. CONCLUSION: The addition of Clamshell exercises to the rehabilitation program resulted in a significantly greater reduction in TEL compared to the control group. These findings suggest that Clamshell exercises were found to be an effective intervention for addressing TEL after ACLR.

Predictive Factors for Extracapsular Extension of Prostate Cancer to Select the Candidates for Nerve-sparing Radical Prostatectomy.

Nerve-sparing radical prostatectomy (NSRP) for prostate cancer (PC) enables better postoperative recovery of continence and potency but may increase the risk of positive surgical margins. This study aimed to investigate preoperative predictive factors for extracapsular extension (ECE) of PC to select patients for NSRP. We retrospectively evaluated 288 patients with PC (576 lobes) diagnosed with 12-core transrectal ultrasound-guided biopsy and magnetic resonance imaging (MRI) who underwent laparoscopic or robot-assisted radical prostatectomy at our institution. Surgical specimens and preoperative parameters (prostate-specific antigen, prostate volume, biopsy and MRI findings, preoperative therapy) were analyzed. Of 576 prostate lobes, the incidence Ipsilateral ECE was identified in 97 (16.8%) lobes. The higher number of unilateral positive biopsy cores, the highest Gleason score 8 or more and positive unilateral findings on MRI are significant higher in prostate sides with ECE in univariate analysis. In multivariate analysis, positive unilateral MRI findings (odds ratio [OR], 2.86; p < 0.001) and unilateral biopsy positive core ≥ 3 (OR, 3.73; p < 0.001) were independent predictors of unilateral ECE. The detection rate of unilateral ECE in those cases with two factors (side-specific positive biopsy core 2 or less and side-specific MRI findings negative) was 7.1% (19/269). Patients with fewer unilateral positive biopsy cores and negative unilateral MRI findings might be good candidates for NSRP.

Design and Execution of In Vitro Polymerase Assays for Measles Virus and Related Mononegaviruses.

Morbilliviruses such as measles virus (MeV) are responsible for major morbidity and mortality worldwide, despite the availability of an effective vaccine and global vaccination campaigns. MeV belongs to the mononegavirus order of viral pathogens that store their genetic information in non-segmented negative polarity RNA genomes. Genome replication and viral gene expression are carried out by a virus-encoded RNA-dependent RNA polymerase (RdRP) complex that has no immediate host cell analog. To better understand the organization and regulation of the viral RdRP and mechanistically characterize antiviral candidates, biochemical RdRP assays have been developed that employ purified recombinant polymerase complexes and synthetic RNA templates to monitor the initiation of RNA synthesis and RNA elongation in vitro. In this article, we will discuss strategies for the efficient expression and preparation of mononegavirus polymerase complexes, provide detailed protocols for the execution and optimization of RdRP assays, evaluate alternative options for the choice of template and detection system, and describe the application of the assay for the characterization of inhibitor candidates. Although MeV RdRP assays are the focus of this article, the general strategies and experimental approaches are readily transferable to related viruses in the mononegavirus order.

Gait analysis of patients with knee osteoarthiritis who can run versus cannot run.

BACKGROUND: Many middle-aged and older adults participate in running to maintain their health and fitness; however, some have to stop running due to osteoarthritis-attributed knee pain. It was unclear whether gait biomechanics and knee physical findings differ between those who can and cannot run. RESEARCH QUESTION: What are the gait and knee physical findings of patients with knee osteoarthritis who remain capable of running in comparison to those who are not capable of running? METHODS: This was a cross-sectional study, which recruited 23 patients over the age of 40 who had been diagnosed with knee osteoarthritis. Their knee joint ranges of motion and muscle strength, knee pain, and the maximum gait speed (walk as fast as possible) were measured. Knee alignment was calculated from X-ray images, and the knee joint extension angle and adduction moment during a self-selected gait speed were determined using motion analysis. Participants were divided into two groups-those able to run (n=11) and those unable to run (n=12). The measured and calculated outcomes were compared between groups, and logistic regression analyses of significantly different outcomes were performed. RESULTS: There were significant group differences in the maximum knee extension angle during stance phase (p = 0.027), maximum gait speed during the 10-m walk test (p = 0.014), knee pain during gait (p = 0.039) and medial proximal tibial angle by X-ray (p = 0.035). Logistic regression analyses revealed that the maximum knee extension angle during stance phase (OR: 1.44, 95%CI: 1.06¬1.94, p = 0.02) was a significant factor. SIGNIFICANCE: The ability to extend the knee during gait is an important contributing factor in whether participants with knee osteoarthritis are capable of running.

Exploring Sociodemographic Factors in Allergic Fungal Rhinosinusitis in a Northern California Patient Population.

BACKGROUND: Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis (CRS) that has previously been associated with younger age and Black patients. However, the role of demographic and socioeconomic factors in AFRS severity remains to be fully elucidated. OBJECTIVE: The objective of this study was to determine whether demographic and socioeconomic factors are associated with incidence of AFRS, as well as with disease severity in Northern California. METHODS: A retrospective cohort study was conducted of adult patients with AFRS and CRS from 2010 to 2019. AFRS was determined by the Bent and Kuhn criteria, and severity was assessed by radiographic evidence of cranioorbital invasion and other clinical parameters. Chi-square and t-test were used to assess demographic and socioeconomic differences between AFRS and CRS cohorts, and multivariable logistic regression was used to assess risk factors for severe AFRS. RESULTS: Black patients represented 26.2% (55/210 patients) of the AFRS group and 4.9% (842/17,300 patients) of the CRS group, with pairwise comparison of race/ethnicity categories showing that the AFRS group had significantly higher proportions of Black race/ethnicity compared with other race/ethnicities (p < 0.01). AFRS and CRS groups differed significantly by age, with mean ages of 48.7 and 51.0 years, respectively (p = 0.04). There were no significant differences in gender, Medicaid status, comorbidities, and socioeconomic status measures. Multivariate logistic regression showed that Black patients had higher odds of having severe AFRS (adjusted odds ratio = 2.29; 95% confidence interval: 1.18-4.45). CONCLUSION: AFRS has a unique predilection for Black patients, and severe disease is also more likely in this population.

Advances in aqueous humor proteomics for biomarker discovery and disease mechanisms exploration: a spotlight on primary open angle glaucoma.

Altered protein levels in the aqueous humor (AH) may be a valuable source of novel biomarkers in neurodegenerative retinal disease. The proximity of this body fluid to the disease focus, and its corresponding enrichment for tissue specific proteins, renders it an excellent matrix to study underlying molecular mechanisms. Novel proteomic methods accordingly hold large potential for insight into pathologies based on the composition of the AH proteome, including primary open angle glaucoma (POAG). Recent mass spectrometry-based studies use novel approaches to tackle the challenges arising from the combination of low available sample volume and protein concentration, thereby increasing proteome coverage. But despite significant improvements in mass spectrometry (MS), a different class of proteomic technologies is poised to majorly impact the analysis of ocular biofluids. Affinity proteomic workflows, having become available commercially recently, have started to complement data obtained by MS and likely will grow into a crucial tool for ophthalmological biomarker research. This review highlights corresponding approaches in proteome analysis of aqueous humor and discusses recent findings on alterations of the AH proteome in POAG.

Methods and clinical biomarker discovery for targeted proteomics using Olink technology.

PURPOSE: This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment. EXPERIMENTAL DESIGN: We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology. RESULTS: Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments. CONCLUSIONS: Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.

Half-life extension of single-domain antibody-drug conjugates by albumin binding moiety enhances antitumor efficacy.

Single-domain antibody-drug conjugates (sdADCs) have been proven to have deeper solid tumor penetration and intratumor accumulation capabilities due to their smaller size compared with traditional IgG format ADCs. However, one of the key challenges for improving clinical outcomes of sdADCs is their abbreviated in vivo half-life. In this study, we innovatively fused an antihuman serum albumin (αHSA) nanobody to a sdADCs targeting oncofetal antigen 5T4, conferring serum albumin binding to enhance the pharmacokinetic profiles of sdADCs. The fusion protein was conjugated with monomethyl auristatin E (MMAE) at s224c site mutation. The conjugate exhibited potent cytotoxicity against various tumor cells. Compared with the nonalbumin-binding counterparts, the conjugate exhibited a 10-fold extended half-life in wild-type mice and fivefold prolonged serum half-life in BxPC-3 xenograft tumor models as well as enhanced tumor accumulation and retention in mice. Consequently, n501-αHSA-MMAE showed potent antitumor effects, which were comparable to n501-MMAE in pancreatic cancer BxPC-3 xenograft tumor models; however, in human ovarian teratoma PA-1 xenograft tumor models, n501-αHSA-MMAE significantly improved antitumor efficacy. Moreover, the conjugate showed mitigated hepatotoxicity. In summary, our results suggested that fusion to albumin-binding moiety as a viable strategy can enhance the therapeutic potential of sdADCs through optimized pharmacokinetics.

Renal Cell Carcinoma With Tumor Thrombus: A Case Series in Puerto Rico.

INTRODUCTION:  Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico (PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. METHODS:  In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12 met the inclusion criteria for the study. Cases were categorized using the latest RCC TT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers. Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and TT extension level. RESULTS:  Most patients lacked TT-related symptoms. The most severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMI greater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% of patients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. CONCLUSION:  RCC is a common renal neoplasm in PR that can present with intravascular tumor extension. Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.

Autologous Rib Cartilage Reconstruction After Silicone Implant Removal in a Patient With Bilateral Cleft Lip and Palate: A Case Report.

Cleft lip rhinoplasty (CLR) corrects nasal deformities in cleft lip and palate patients. However, limitations exist in some countries like Japan regarding the use of silicone implants for CLR. While historical reports mention their use since the 1980s, long-term data is lacking. This case report describes a 53-year-old Japanese woman with bilateral cleft lip and palate who received a CLR with a silicone implant over 30 years ago. The implant calcified, causing nasal dorsum skin hardening and thinning, raising concerns of extrusion. To prevent potential extrusion, the implant was removed and replaced with autologous seventh rib cartilage grafts. Various grafting techniques were used for basal support, dorsal augmentation, and nasal tip refinement. The postoperative evaluation showed excellent results with no complications. This case highlights the importance of long-term follow-up after CLR with silicone implants and advocates for autologous rib cartilage as a reliable alternative. Reporting such cases is crucial for informing patient management and research on the long-term safety of silicone implants in CLR.