Citations

Abstract Glaucoma is characterized by programmed cell death of retinal ganglion cells (RGCs) after axonal injury. Several studies have shown the cell-intrinsic drivers of RGC degeneration act in a compartment-specific manor. Recently, the transcription factors JUN and DDIT3 were identified as critical hubs regulating RGC somal loss after mechanical axonal injury. It is possible somal DDIT3 and JUN activity initiates axonal degeneration mechanisms in glaucoma. Alternatively, DDIT3 and JUN may act downstream of inciting degenerative mechanisms and only drive RGC somal loss. The MAP2Ks MKK4 and MKK7 control all JNK and JUN activity and can indirectly activate DDIT3. Furthermore, MKK4 and MKK7 have been shown to drive RGC axonal degeneration after mechanical axonal injury. The present work investigated whether JUN and DDIT3, or their upstream activators MKK4 and MKK7, control degeneration of RGC axons and somas after glaucoma-relevant injury. Ddit3 and Jun deletion did not prevent axonal degeneration in ocular hypertensive DBA/2J mice but prevented nearly all RGC somal loss. Despite robust somal survival, Ddit3 and Jun deletion did not preserve RGC somal viability (as assessed by PERG decline and soma shrinkage) in DBA/2J mice or after glaucoma-relevant mechanical axonal injury. In contrast, Mkk4 and Mkk7 deletion significantly lessened degeneration of RGC somas and axons, and preserved somal function and size after axonal injury. In summary, activation of MKK4 and MKK7 appears to be the inciting mechanism governing death of the entire RGC after glaucoma-relevant injury; driving death of the RGC soma (likely through activation of DDIT3 and JUN), decline in somal viability, and axonal degeneration via DDIT3 and JUN-independent mechanisms.

Black patients with metastatic prostate cancer have higher mortality rates compared to non-Hispanic White patients. There are no data on outcomes with [177Lu]Lu-PSMA-617 (LuPSMA) across racial groups. We evaluated the association between race and outcomes with LuPSMA in a multi-institutional cohort of consecutive patients with mCRPC treated with LuPSMA. The primary outcomes were PSA-50 rate, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Statistical models were adjusted for age, number of prior therapies, sites of metastases, and baseline PSA. A total of 654 patients were included; 593 (91%) were White, 45 (7%) were Black and 16 (2%) were another non-Black minority (NBM). There were no statistically significant differences in PSA-50 rates, PSA-PFS and OS between the groups. Black and White patients treated with LuPSMA had similar clinical outcomes; efforts are needed to ensure Black and NBM patients have equal access to life prolonging therapies to narrow disparities in outcomes.

The NCCN Guidelines for Survivorship include screening, evaluation, and treatment recommendations for common physical and psychosocial problems resulting from adult-onset cancer and its treatment and provide a framework for coordination of survivorship care. They also include recommendations to help cancer survivors enhance their wellness and maintain a healthy lifestyle. These NCCN Guidelines Insights summarize the panel’s current recommendations and recent updates regarding physical activity, nutrition, and weight management for cancer survivors.

ABSTRACT Introduction Improving organ preservation is essential for expanding the donor pool and enhancing outcomes for pediatric transplant recipients. This report presents three pediatric patients who received donor hearts preserved using the Organ Care System (OCS). All donor hearts were prepared, placed, and monitored on OCS according to standard protocols. Heart function and myocardial edema were visually assessed during monitoring. Case Reports Patient 1: A 17‐year‐old female patient with hypertrophic cardiomyopathy utilized OCS technology due to donor distance. She experienced an uncomplicated post‐transplant course and was discharged on post‐transplant day 10. Patient 2: A 14‐year‐old male patient with complex congenital heart disease, palliated with Fontan circulation, underwent orthotopic heart transplantation (OHT) with OCS support due to both the complexity of the procedure and donor heart distance. His post‐transplant course was complicated by a revision of the ascending aorta anastomosis and prolonged milrinone infusion for diastolic dysfunction. He was discharged on post‐transplant day 31. Patient 3: A 16‐year‐old male patient with hypoplastic left heart syndrome, also palliated with Fontan circulation, underwent OHT using OCS technology due to the complexity of the surgical procedure. His post‐transplant recovery was unremarkable, and he was discharged on post‐transplant day 15. Conclusions All three pediatric patients demonstrated favorable short‐term outcomes using OCS technology. The OCS system facilitated shorter ischemic times despite the need for extended transport distances or complex surgical procedures. However, further studies with larger patient cohorts and longer follow‐up are needed to better understand the long‐term impact of OCS on pediatric heart transplantation outcomes.

Abstract Aim Growing evidence suggests that immune/inflammatory pathways play a crucial role in the persistence of symptoms in diverticular disease (DD). We hypothesize that chronic diverticulitis triggers a self‐sustained inflammatory status which can be detected by measuring the levels of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). The aim of this study was to investigate the systemic levels of TNF‐α and IL‐6 before and after elective surgery in patients with DD, and their relationship with the gastrointestinal quality of life index (GIQLI) score. Method This prospective multicentric study enrolled patients from the Diverticular Disease Registry (DDR‐Trial, NCT04907383). All adult patients diagnosed with symptomatic uncomplicated diverticular disease (SUDD), uncomplicated recurrent diverticulitis (URD) and smouldering diverticulitis (SmD) between 1st December 2022 and 31st December 2023 were included in this study. Exclusion criteria were as follows: no surgery, a concurrent chronic immunomodulated systemic disease, a SARS‐CoV‐2‐positive test in the previous 12 months, a history of cancer in the previous 5 years, patients treated with immunomodulators, an American Society of Anesthesiologists category of class IV, and complicated acute diverticulitis. Results Seventy‐two patients were included: 52 (72%) with URD, 11 (15%) with SUDD, and nine (13%) with SmD. The median postsurgery – presurgery (Δ)IL‐6 and ΔTNF‐α levels were −16.8 and −17.3 pg/mL, respectively ( p < 0.001 for both; Wilcoxon test). Spearman correlation revealed a significant, negative association between the ΔGIQLI and the ΔIL‐6, as well as the ΔTNF‐α ( p < 0.001 for both). Greater reduction in the levels of IL‐6 and TNF‐α following surgery are associated with higher GIQLI scores postoperatively. Conclusion Patients with chronic diverticulitis may experience persistent systemic inflammation driven by a colonic trigger. Surgical removal of this trigger appears to enhance GIQLI outcomes reducing IL‐6 and TNF‐α across surgery.

Background: Periarticular local infiltration analgesia has become an important mainstay of multimodal analgesia after elective total hip arthroplasty (THA). However, the role of novel motor-sparing fascial plane blocks—with or without periarticular local infiltration analgesia—has not been fully elucidated for patients undergoing THA. The authors conducted a network meta-analysis evaluating the relative analgesic effectiveness of motor-sparing fascial plane blocks (quadratus lumborum, erector spinae, and pericapsular nerve group blocks) and periarticular local infiltration analgesia for adult patients undergoing THA. Methods: Randomized trials examining single-injection quadratus lumborum, erector spinae, or pericapsular nerve group blocks, or periarticular local infiltration analgesia, for THA were sought. The primary outcome was area under the curve (AUC) rest pain scores during the period from 0 to 24 h. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 h; postoperative function at 6, 12, and 24 h; analgesic consumption at 0 to 24 h; incidence of opioid-related side effects; and incidence of block-related complications. Network meta-analysis was performed using a frequentist approach. Results: A total of 44 trials (3,579 patients) evaluating the quadratus lumborum block, erector spinae block, pericapsular nerve group block, or periarticular local infiltration analgesia for THA were considered. Network meta-analysis was used to derive the probability of each intervention being the most effective as compared to the others (P score). For AUC 0 to 24 h rest pain, periarticular local infiltration analgesia was the most effective intervention, as demonstrated by a P score of 89%. For postoperative analgesic consumption, the quadratus lumborum block was the most effective intervention, with a P score of 88%. This was followed by the pericapsular nerve group block (74%), the erector spinae block (38%), and periarticular local infiltration analgesia (42%). Conclusions: Periarticular local infiltration analgesia alone provides the most consistent improvements in postoperative rest pain, analgesic consumption, and functional recovery after THA. The addition of a quadratus lumborum block or pericapsular nerve group block to periarticular local infiltration may further improve analgesic outcomes.

BACKGROUND AND OBJECTIVES: It remains unclear whether decompressive craniectomy (DC) is beneficial in patients who suffer symptomatic intracerebral hemorrhage (sICH) after acute ischemic stroke (AIS). We sought to study the effect of DC on functional outcomes in patients with sICH after AIS who underwent mechanical thrombectomy (MT). METHODS: Patients with AIS from anterior circulation large vessel occlusion who underwent MT and subsequently developed sICH were identified from the Stroke Thrombectomy and Aneurysm Registry database. The primary outcome was acceptable 90-day functional neurological outcome, defined as modified Rankin scale (mRS) 0-3. Multivariable logistic regression and propensity-score matching were used to identify and quantify risk factors. RESULTS: Of 464 patients identified with sICH after AIS after MT, 97 patients (20.9%) underwent DC. Patients who underwent DC were more likely to be female ( P < .001), younger ( P < .001), have a measured medical comorbidity, have higher baseline mRS ( P = .02), and have higher-grade hemorrhages ( P = .01). At 90 days, 14% of patients had the primary outcome of mRS 0-3 and 56% had died. The primary outcome was observed in 11 patients who underwent DC (11%) and 55 (15%) of those without DC (odds ratio [OR] 0.7, 95% CI 0.4-1.4, P = .40). DC did not affect mRS shift at 90 days ( P = .10) but was associated with lower mortality (OR 0.5, 95% CI 0.3-0.8, P = .01). Multivariable analysis demonstrated that DC decreased the odds of primary outcome (adjusted OR 0.2, 95% CI 0.02-0.9, P = .045), but did not affect mortality ( P = .94), mRS shift ( P = .50), or length of stay ( P = .90). Propensity-matched analysis similarly demonstrated that non-DC patients were more likely to achieve the primary outcome (24% vs 8%, P = .045). CONCLUSION: In patients with sICH after AIS after MT, those selected for DC had less favorable outcomes and similar rates of mortality at 90 days.

This manuscript summarizes the first part of the proceedings of the 2023 Dublin ISUP Consensus Conference encompassing the best practice recommendations on the pathology of neoplasms of urachal origin. The rationale for convening this consensus conference was the lack of structured and consented histopathologic recommendations in these rare tumors. Consensus among the meeting participants (n=80) was reached on the following statements: (1) combination of gross, histologic, clinical and imaging findings with exclusion of secondary tumor metastasis are to be used in the diagnosis of urachal carcinoma; (2) the 2022 World Health Organization (WHO) separate criteria for the diagnosis of urachal adenocarcinoma and for nonglandular carcinoma should be applied; (3) specific elements are to be evaluated and recorded in the gross examination of resection specimens containing urachal tumors; (4) sampling considerations for resection specimens containing urachal tumors are advised; (5) participants are against using 5% or 10% cutoff for the extent of intraepithelial carcinoma in urachal mucinous cystic tumor of low malignant potential; (6) use of immunohistochemical markers for the differential diagnosis of urachal adenocarcinomas in transurethral resection (TUR) specimen is considered optional; (7) similar tumor classificatory (nosology) rules for carcinomas arising from bladder mucosa (eg, urothelial carcinoma, squamous cell carcinoma, and neuroendocrine carcinoma) should be applied for nonglandular urachal carcinomas; (8) a new staging approach other than the previously proposed systems should be designed for urachal carcinoma; (9) a system modifying the current Tumor-Node-Metastasis (TNM)/American Joint Committee on Cancer (AJCC) staging system for urinary bladder cancer is considered appropriate for a study in urachal carcinoma; and (10) several histologic elements are to be reported when diagnosing urachal carcinoma in TUR and resection specimens. This report from the Dublin ISUP consensus conference will serve as a practice recommendation for pathologists and as a guide for future standardized reporting protocols and research regarding urachal tumors. In addition, an international database for urachal cancers under the guidance of ISUP is being planned to be established to address pertinent issues in the pathology of urachal cancers.

Objective To assess integration of a single-use robotic-assisted cochlear implant (RA-CI) electrode array insertion system into surgical workflows, identify potential challenges, and inform best practices. Study Design Survey. Setting Survey data from 16 surgeons across 10 US hospitals. Patients CI candidates 12 years and older with radiographically normal cochleae. Intervention CI surgery with single-use RA-CI insertion system during electrode array insertion. Main Outcome Measures Number of RA-CI to achieve proficiency, estimated additional time for RA-CI, and best practices to successfully incorporate the RA insertion system into CI surgery. Results A total of 121 RA-CI cases were performed. All surgeons completed the survey. Most surgeons (62.5%) reported they would feel comfortable using the device within five cases. Eight (50%) reported use of the RA system added 5 to 10 minutes to the case, and seven (44%) reported an added 10–15 minutes. Providing adequate incision size to secure the unit base superior to the temporal line and maximizing exposure of the facial recess were the most recommended best practices. Additional recommendations included pulling the receiver/stimulator forward within the pocket to facilitate a full electrode array insertion and considering drive head placement and mastoidectomy size to maximize overall visibility during electrode array insertion. Conclusions Proficiency with an RA electrode array insertion system during CI surgery can be achieved with minor adjustments to the surgical approach, within relatively few use cases (generally <5) and with minimal time addition (between 5 and 15 min). Training to specific best practices is important before initial clinical use.