Single Port Robotic Nephrectomy via lower anterior retroperitoneal approach: feasible, safe and effec-tive option in surgically complex patients.

PURPOSE: Minimally invasive radical nephrectomy is often preferred for larger renal tumours not suitable for partial nephrectomy (1). When performed with a multiport robot, the procedure is routinely performed with a transperitoneal approach, with recent studies highlighting important factors for surgical outcomes, including predictive factors (2), segmental artery unclamping techniques (3), and comparisons of robotic techniques (4). This video shows that SP Robot-Assisted Radical Nephrectomy (RARN) via a lower anterior approach is valuable in challenging cases. MATERIALS AND METHODS: We performed SP-RARN on two complex patients using a retroperitoneal lower anterior approach. The first patient, a 54-year-old female with a BMI of 36.8 kg/m², had a ventral hernia and bowel obstruction history, with a 9 cm right middle kidney mass. The second patient, a 58-year-old male with a BMI of 31.19 kg/m², had ESRD and was on peritoneal dialysis for 8 years, with a 3.4x3.7 cm mass in the right superior pole, suspected to be RCC. The surgical technique is detailed in the video. RESULTS: Both procedures were successful, with operative times of 173 and 203 minutes and blood loss of 150 mL. No complications occurred. Patients were discharged after 31 and 38 hours, respectively. Histopathology confirmed RCC. At the 3-month follow-up, no complications or readmissions were reported. Second patient continued peritoneal dialysis without issues. CONCLUSION: Retroperitoneal SP-RARN via the lower anterior approach avoids the peritoneal cavity, making it suitable for certain patients. In these patients, more so than in others, this procedure is feasible, safe, and less morbid than the standard multiport approach.

Refractive Surgery Patient Characteristics Associated With Satisfaction Scores.

PURPOSE: To determine factors influencing patient satisfaction scores in recipients of refractive surgery. METHODS: In this prospective survey-based study, patients who had refractive surgery at an outpatient refractive clinic completed a survey of selected questions from the Press Ganey survey and the National Eye Institute Visual Function Questionnaire-25. Correlation between patient-specific variables and survey questions were assessed using Student's t-tests. RESULTS: Fifty-three patients were recruited over a 3-year period. Most were male (55%) and middle aged (mean age: 34 years). Eleven percent underwent photorefractive keratectomy surgery and the rest had laser in situ keratomileusis, with no complications. Twenty-four percent of surveyed patients reported mild to moderate eye pain postoperatively, with the rest reporting no pain. All patients reported a full score for overall satisfaction. CONCLUSIONS: This study found persistent high patient satisfaction score across a variation of characteristics, suggesting that optimal scores are mainstay after refractive surgery procedures with excellent visual outcomes, independent of patient clinical and sociodemographic characteristics. [J Refract Surg. 2024;40(8):e539-e543.].

Contemporary management of ischemic priapism: A 12-year population-based analysis from a large US database.

BACKGROUND: Priapism is a urological condition characterized by a persistent erection. The management varies based on its subclassifications. Despite established clinical guidelines for ischemic priapism, there is a lack of large-scale research focused on patient characteristics and management strategies. OBJECTIVES: To analyze the contemporary management of ischemic priapism in the US, exploring patient demographics and clinical characteristics, as well as predictors of erectile dysfunction (ED) and penile prosthesis implantation (PPI). MATERIALS AND METHODS: We performed a retrospective analysis of the PearlDiver Mariner database, reviewing records from 2010-2021. Adult males diagnosed with ischemic priapism were included. Data analysis covered demographic, clinical variables, and management strategies. Predictors of de novo ED and PPI were evaluated using multivariable logistic regression analysis. RESULTS: Of 36,120 patients, most (93%) received only medical management, and a minority underwent surgical interventions (penile shunt surgery [PSS], PPI or both). Medical management was typically effective, as 67.08% of the patients in this group experienced only one episode of priapism. However, de novo ED occurred in 16.57% of these patients. The majority of patients undergoing PPI had an inflatable prosthesis (81%). Older age (odds ratio, OR 1.02), the presence of metabolic diseases (OR 1.39), neurogenic disorders (OR 1.72), solid pelvic malignancies (OR 1.09), and multiple episodes of priapism were identified as significant predictors of de novo ED (all p < 0.05). Similarly, age (OR 1.03), the presence of metabolic diseases (OR 1.23), solid pelvic malignancies (OR 1.99), and multiple episodes of priapism were associated with higher likelihood of PPI (all p < 0.05). CONCLUSION: Most cases of ischemic priapism are managed with the medical therapy. Less than 3% of patients with ischemic priapism receive PPI, and when this occurs an inflatable prosthesis is favored. Age, specific comorbidities, and multiple episodes of priapism appear to be significant predictors of ED and PPI.

Facultative parthenogenesis discovered for the first time in Jamaican boa (Chilabothrus subflavus) using novel microsatellite markers.

The mode of reproduction most often seen in snakes is sexual, but studies have noted facultative parthenogenesis in at least six families. Here, we provide evidence for the first observed case of facultative parthenogenesis in a captive Jamaican boa (Chilabothrus subflavus). A 7-year-old female Jamaican boa, isolated since birth, was found to have produced a litter of 15 offspring. To provide molecular DNA evidence of parthenogenesis, 13 new microsatellite loci were isolated in the species. All offspring were found to be homozygous at each locus and only possess alleles found in the dam, implicating that they were born from asexual reproduction. Several developmental abnormalities, including stillbirths and spinal deformities, were noted in the litter which may be explained by their increased level of homozygosity. To preserve genetic diversity in the captive population, research should be conducted to understand the prevalence of this mode of reproduction and to guide future management decisions of this IUCN listed Vulnerable species.

Residency in Long-Term Care Facilities: An Important Risk Factor for RSV Hospitalization.

Older age and comorbid conditions increase risk for severe RSV. Skilled nursing (SNF) and assisted living (AL) facilities represent an intersection of risk factors. In a 3-year prospective study (Rochester, NY) we compared population-based incidence of RSV-associated hospitalization for community-dwelling, SNF and AL adults ≥65 years. Median age was 76, 83 and 86 years, respectively, and dementia and CHF more prevalent among SNF and assisted living residents. Average annual incidence was 117 (95%CI:104-132), 440 (95%CI:307-629) and 740/100,000 persons (95%CI:523-1045) for community-dwelling, SNF and AL adults ≥65 years, respectively, demonstrating need for unequivocal RSV vaccine recommendations in SNF and AL residents.

Urachal Carcinoma: Insights From a National Database.

INTRODUCTION: Urachal carcinoma (UrC) is a rare, nonurothelial malignancy, comprising less than 1% of all bladder cancers. It usually affects males in their fifth to sixth decade and is often diagnosed at an advanced stage with metastasis. This study examines UrC population characteristics and management. METHODS: We identified UrC patients from bladder biopsies or TURB in the PearlDiver Mariner database (2010-2022). Descriptive statistics detailed patient characteristics. Student's T-Tests compared ages for partial vs. radical cystectomy, and Fisher's exact test compared SDOH presence. Significance was set at P < .05. Analyses used R version 3.6.0 within PearlDiver's software. RESULTS: Among 2475 UrC patients (mean age 69.2 ± 9.2 years, 73.1% men), most were in the south (36.5%), outpatient settings (84.5%), and privately insured (65.3%). A total of 418 (16.2%) had at least 1 SDOH. Imaging before diagnosis was used in 65.74% of patients, primarily ultrasound. Smoking was present in 54.5%, diabetes in 42.9%, and obesity in 25.2%. After diagnosis, 1246 (50.34%) had localized disease; 407 underwent radical cystectomy and 330 partial cystectomy. Patients undergoing radical cystectomy were older (66.74 ± 8.13 years) compared to those undergoing partial cystectomy (60.55 ± 12.92 years) (P < .001), with SDOH factors more prevalent in the partial cystectomy group (P = .03). CONCLUSION: UrC is a rare, often advanced-stage cancer predominantly affecting older men. Our study shows a trend towards partial cystectomy for localized UrC. Further research is needed to personalize surgery and integrate multidisciplinary approaches for better outcomes.

Identification of Meibomian gland stem cell populations and mechanisms of aging.

Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identified markers for stem cell populations that maintain distinct regions of the gland and uncovered Hh signaling as a key regulator of stem cell proliferation. Consistent with this, human Meibomian gland carcinoma exhibited increased Hh signaling. Aged glands displayed decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.

Leflunomide-Associated Wound Complication After Cochlear Implantation: A Case Report.

INTRODUCTION: Cochlear implantation has become an increasingly common strategy for aural rehabilitation in patients with severe to profound hearing loss who no longer benefit from conventional amplification. In conjunction, immunosuppressive therapies (e.g. disease-modifying anti rheumatic drugs (DMARDs) have become the keystone of management in numerous autoimmune conditions. Given the increasing prevalence of both, a greater proportion of patients will undergo cochlear implantation while on immune-modulating medications. While these medications are usually well tolerated, immunosuppression may put patients a higher risk for device infections. At present, this is not extensively studied within the cochlear implant literature. METHODS: We conducted a retrospective chart review and review of the literature.Results:We present the case of an 81-year-old male who experienced wound dehiscence and infection secondary to leflunomide use for treatment of rheumatoid arthritis. Resolution of these issues was noted with a therapeutic drug holiday, and the patient has subsequently undergone re-implantation without issue.Conclusions:The case highlights a potential CI-associated wound complication in the setting of DMARD therapy. Given the increasing prevalence of both CIs and immunosuppressive therapy, future study on the potential for interaction is warranted to identify the best management strategy in the perioperative setting.

Unresolved questions regarding cellular cysteine sources and their possible relationships to ferroptosis.

Cysteine is required for synthesis of glutathione (GSH), coenzyme A, other sulfur-containing metabolites, and most proteins. In most cells, cysteine comes from extracellular disulfide sources including cystine, glutathione-disulfide, and peptides. The thioredoxin reductase-1 (TrxR1)- or glutathione-disulfide reductase (GSR)-driven enzymatic systems can fuel cystine reduction via thioredoxins, glutaredoxins, or other thioredoxin-fold proteins. Free cystine enters cells thorough the cystine-glutamate antiporter, xCT, but systemically, plasma glutathione-disulfide might predominate as a cystine source. Erastin, inhibiting both xCT and voltage-dependent anion channels, induces ferroptotic cell death, so named because this type of cell death is antagonized by iron-chelators. Many cancer cells seem to be predisposed to ferroptosis, which has been proposed as a targetable cancer liability. Ferroptosis is associated with lipid peroxidation and loss of either glutathione peroxidase-4 (GPX4) or ferroptosis suppressor protein-1 (FSP1), which each prevent accumulation of lipid peroxides. It has been suggested that an xCT inhibition-induced cellular cysteine-deficiency lowers GSH levels, starving GPX4 for reducing power and allowing membrane lipid peroxides to accumulate, thereby causing ferroptosis. Aspects of ferroptosis are however not fully understood and need to be further scrutinized, for example that neither disruption of GSH synthesis, loss of GSH, nor disruption of glutathione disulfide reductase (GSR), triggers ferroptosis in animal models. Here we reevaluate the relationships between Erastin, xCT, GPX4, cellular cysteine and GSH, RSL3 or ML162, and ferroptosis. We conclude that, whereas both Cys and ferroptosis are potential liabilities in cancer, their relationship to each other remains insufficiently understood.

ASO Visual Abstract: Open Versus Minimally Invasive Nephroureterectomy: Contemporary Analysis from a Wide National Population-Based Database.

Contemporary trend analysis of a large national data set confirms the occurrence of a significant shift toward minimally invasive nephroureterectomy (MINU), which is gradually replacing open nephroureterectomy (ONU). A minimally invasive approach is associated with a lower risk of complications. Social determinants of health (SDOH) are non-clinical factors that ultimately may have an impact on the outcomes of the nephroureterectomy (NU) procedure ( https://doi.org/10.1245/s10434-024-15565-6 ).

Chemotherapy-induced intestinal epithelial damage directly promotes galectin-9-driven modulation of T cell behavior.

The intestine is vulnerable to chemotherapy-induced damage due to the high rate of intestinal epithelial cell (IEC) proliferation. We have developed a human intestinal organoid-based 3D model system to study the direct effect of chemotherapy-induced IEC damage on T cell behavior. Exposure of intestinal organoids to busulfan, fludarabine, and clofarabine induced damage-related responses affecting both the capacity to regenerate and transcriptional reprogramming. In ex vivo co-culture assays, prior intestinal organoid damage resulted in increased T cell activation, proliferation, and migration. We identified galectin-9 (Gal-9) as a key molecule released by damaged organoids. The use of anti-Gal-9 blocking antibodies or CRISPR/Cas9-mediated Gal-9 knock-out prevented intestinal organoid damage-induced T cell proliferation, interferon-gamma release, and migration. Increased levels of Gal-9 were found early after HSCT chemotherapeutic conditioning in the plasma of patients who later developed acute GVHD. Taken together, chemotherapy-induced intestinal damage can influence T cell behavior in a Gal-9-dependent manner which may provide novel strategies for therapeutic intervention.

The relationship between neighborhood socioeconomic status and short-term outcomes following colon resection.

BACKGROUND: This study investigates the association between neighborhood socioeconomic status, measured by the Distressed Communities Index (DCI), and short-term outcomes following colon resection. METHODS: Utilizing the Maryland State Inpatient Sample database (SID 2018-2020), we determined the association between DCI and post-op outcomes following colon resection including length of stay, readmissions, 30-day in-hospital mortality, and non-routine discharges. Multivariate regression analysis was performed to control for potential confounding factors. RESULTS: Of the 13,839 patients studied, median age was 63, with 54.3 â€‹% female and 64.5 â€‹% elective admissions. Laparoscopic surgery was performed in 36.9 â€‹% cases, with a median hospital stay of 5 days. Patients in distressed communities faced higher risks of emergency admission (OR: 1.31), prolonged hospitalization (OR: 1.29), non-routine discharges (OR: 1.36), and readmission (OR: 1.33). Black patients had longer stays than White patients (OR: 1.3). Despite adjustments, in-hospital mortality did not significantly differ among neighborhoods. CONCLUSION: Our study reveals that patients residing in distressed neighborhoods face a higher risk of prolonged hospitalization, non-routine discharges, and readmission rate after colon resection.

Patient-Reported Outcomes and Higher Order Aberrations Following Topography-Guided Femtosecond Laser-Assisted In Situ Keratomileusis.

PURPOSE: To examine patient-reported outcomes and higher order aberrations following topography-guided laser-assisted in situ keratomileusis (LASIK). METHODS: This was a prospective, nonrandomized observational study at a single academic center. Sixty eyes from 30 patients underwent bilateral topography-guided femtosecond LASIK for correction of myopia using the VisuMax 500 femtosecond laser (Zeiss; Oberkochen, Germany) and Allegretto Wave Eye-Q 400 Hz Excimer Laser (Alcon/Wavelight; Erlangen, Germany) with the Contoura topography system (Alcon; Geneva, Switzerland) for topography-modified refraction. The main outcomes of this study were higher order aberrations (HOAs) and results from the Patient-Reported Outcomes with LASIK questionnaire. RESULTS: There was a small, significant increase in HOA root mean square, spherical aberration, and coma at 1, 3, 6, and 12 months following topography-guided LASIK (all P < 0.05), but no change in trefoil. In addition, self-reported worry related to vision (P < 0.001) and ability to perform activities (P < 0.001) significantly improved after surgery. The prevalence of double images, glare, halos, or starbursts decreased from 73% preoperatively to 56%, and no participants reported "very" or "extremely" bothersome visual symptoms after 12 months. Dry eye symptoms per Ocular Surface Disease Index score decreased significantly at 6 (P = 0.01) and 12 (P = 0.002) months after surgery. There was a 100% satisfaction rate with visual outcomes and duration of time to improvement in vision following the procedure. CONCLUSIONS: Although there was an increase in HOAs following topography-guided LASIK, there were significant improvements in the presence of double images, glare, halos, and starbursts and vision-related quality-of-life metrics. Overall satisfaction rates in this study were high.

Open versus Minimally Invasive Nephroureterectomy: Contemporary Analysis from a Wide National Population-Based Database.

BACKGROUND: It is generally perceived that minimally invasive nephroureterectomy (MINU), especially in the form of robotic-assisted laparoscopy, is gaining an increasing role in many institutions. OBJECTIVE: The aim of our study was to investigate contemporary trends in the adoption of MINU in the United States compared with open nephroureterectomy (ONU). METHODS: Patients who underwent ONU or MINU between 2011 and 2021 were retrospectively analyzed using PearlDiver Mariner, an all-payer insurance claims database. International Classification of Diseases diagnosis and procedure codes were used to identify the type of surgical procedure, patients' characteristics, social determinants of health (SDOH), and perioperative complications. The primary objective assessed different trends and costs in NU adoption, while secondary objectives analyzed factors influencing the postoperative complications, including SDOH. Outcomes were compared using multivariable regression models. RESULTS: Overall, 15,240 patients underwent ONU (n = 7675) and MINU (n = 7565). Utilization of ONU declined over the study period, whereas that of MINU increased from 29 to 72% (p = 0.01). The 60-day postoperative complication rate was 23% for ONU and 19% for MINU (p < 0.001). At multivariable analysis, ONU showed a significantly higher risk of postoperative complications (odds ratio 1.33, 95% CI 1.20-1.48). Approximately 5% and 9% of patients reported at least one SDOH at baseline for both ONU and MINU (p < 0.001). CONCLUSIONS: Contemporary trend analysis of a large national dataset confirms that there has been a significant shift towards MINU, which is gradually replacing ONU. A minimally invasive approach is associated with lower risk of complications. SDOH are non-clinical factors that currently do not have an impact on the outcomes of nephroureterectomy.

Characteristics, trends, and management of Penile cancer in the United States: A population-based study.

BACKGROUND: Penile cancer (PeCa) is a rare disease. HPV infection, smoking, phimosis, and lichen sclerosus represent well-known associated risk factors. OBJECTIVES: Primary aim of our study is to evaluate the incidence and risk factors of PeCa and to outline the adopted diagnostic and therapeutic approaches. Secondary aim is to investigate risk factors associated with aggressive disease and to identify the complications arising from its surgical treatment. MATERIALS AND METHODS: We conducted a retrospective analysis using the PearlDiver™ Mariner database, from January 1, 2011, to December 31, 2021, identifying all patients diagnosed with PeCa and PeIN, evaluating comorbidities, risk factors, and social and economic conditions. We evaluated the imaging modalities employed for staging as well as the treatment strategies. Finally, we evaluated the most frequent complications associated with inguinal lymphadenectomy (ILND). RESULTS: During the study period, 17,494 patients were diagnosed with PeCa and 5,965 with penile intraepithelial neoplasia (PeIN). US was the most frequently utilized imaging modality, followed by PET and PET/CT. Use of CT and MRI was around 5%. Surgical treatment was the predominant strategy, utilized in 31.3% of PeCa and 22.9% of PeIN. Wide Local Excision/Glansectomy emerged as the most common surgical procedures. MLR analysis identified smoking as a risk factor for metastatic PeCa (OR; 95% CI = 1.49; 1.379-1.609), HPV infections were associated with a 35% decrease in risk (OR; 95% CI = 0.65; 0.562-0.744) (all P < 0.001). Lichen sclerosus and phimosis were associated with a doubled risk of demolitive surgery. Approximately 40% of patients experienced complications associated with ILND. CONCLUSION: Despite advances in PeCa management, there's no significant move toward more conservative treatments. Surgical treatments are still marked by high rates of complications, potentially affect the sexual and psychosocial health of patients. These issues may foster a tendency toward avoidance behaviors, contributing to a delayed clinical presentation and treatment.

Systematic engineering for production of anti-aging sunscreen compound in Pseudomonas putida.

Sunscreen has been used for thousands of years to protect skin from ultraviolet radiation. However, the use of modern commercial sunscreen containing oxybenzone, ZnO, and TiO2 has raised concerns due to their negative effects on human health and the environment. In this study, we aim to establish an efficient microbial platform for production of shinorine, a UV light absorbing compound with anti-aging properties. First, we methodically selected an appropriate host for shinorine production by analyzing central carbon flux distribution data from prior studies alongside predictions from genome-scale metabolic models (GEMs). We enhanced shinorine productivity through CRISPRi-mediated downregulation and utilized shotgun proteomics to pinpoint potential competing pathways. Simultaneously, we improved the shinorine biosynthetic pathway by refining its design, optimizing promoter usage, and altering the strength of ribosome binding sites. Finally, we conducted amino acid feeding experiments under various conditions to identify the key limiting factors in shinorine production. The study combines meta-analysis of 13C-metabolic flux analysis, GEMs, synthetic biology, CRISPRi-mediated gene downregulation, and omics analysis to improve shinorine production, demonstrating the potential of Pseudomonas putida KT2440 as platform for shinorine production.

A Randomized Crossover Trial Evaluating the Impact of Cultural Dexterity Training on Surgical Residents' Knowledge, Cross-Cultural Care, Skills, and Beliefs: The Provider Awareness and Cultural dexterity Training for Surgeons (PACTS) Trial.

OBJECTIVES: This trial examines the impact of the Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) curriculum on surgical residents' knowledge, cross-cultural care, skills, and beliefs. SUMMARY BACKGROUND DATA: Cross-cultural training of providers may reduce healthcare outcome disparities, but its effectiveness in surgical trainees is unknown. METHODS: PACTS focuses on developing skills needed for building trust, working with patients with limited English proficiency, optimizing informed consent, and managing pain. The PACTS trial was a randomized crossover trial of 8 academic general surgery programs in the United States: The Early group ("Early") received PACTS between Periods 1 and 2, while the Delayed group ("Delayed") received PACTS between Periods 2 and 3. Residents were assessed pre- and post-intervention on Knowledge, Cross-Cultural Care, Self-Assessed Skills, and Beliefs. Chi-square and Fisher's exact tests were conducted to evaluate within- and between-intervention group differences. RESULTS: Of 406 residents enrolled, 315 were exposed to the complete PACTS curriculum. Early residents' Cross-Cultural Care (79.6% to 88.2%, P<0.0001), Self-Assessed Skills (74.5% to 85.0%, P<0.0001), and Beliefs (89.6% to 92.4%, P=0.0028) improved after PACTS; Knowledge scores (71.3% to 74.3%, P=0.0661) were unchanged. Delayed resident scores pre- to post-PACTS showed minimal improvements in all domains. When comparing the two groups at Period 2, Early residents had modest improvement in all 4 assessment areas, with statistically significant increase in Beliefs (92.4% vs 89.9%, P=0.0199). CONCLUSION: The PACTS curriculum is a comprehensive tool that improved surgical residents' knowledge, preparedness, skills, and beliefs, which will help with caring for diverse patient populations.