Citations

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder. It is primarily caused by pathogenic variants in the PKD1 or PKD2 genes. This leads to the development of numerous kidney cysts, which can result in kidney enlargement and progression to kidney failure. Pain is a common symptom in ADPKD and can negatively affect quality of life (QOL). This pain is often due to the continuous growth of kidney and liver cysts or associated cystic complications. We present a case of a 29-year-old woman with ADPKD who experienced chronic, refractory right-sided flank pain that significantly affected her QOL. Her pain persisted despite taking daily multimodal analgesics and undergoing multiple invasive interventions. She had an unusual asymmetric disease with the right kidney accounting for only 24% of her kidney function. After exhausting all other pain control strategies, she underwent right nephrectomy and partial hepatectomy, which led to substantial improvement in pain and QOL. This review describes the causes, manifestations, and management strategies for abdominal and/or flank pain in ADPKD, including a practical stepwise algorithm to guide clinicians in managing pain and improve QOL of patients with ADPKD. Pain in ADPKD can either be acute or chronic and can lead to significant physical and psychologic distress. Effective pain management in ADPKD requires a multidisciplinary approach, incorporating both nonpharmacologic and pharmacologic interventions such as gabapentin or tolvaptan in select cases. Interventions considered in ADPKD pain control include cyst aspiration with sclerotherapy, celiac plexus blockade, spinal cord stimulation, renal denervation, or nephrectomy.

ABSTRACTIn Functional Magnetic Resonance Imaging (fMRI), the primary contrast is Blood Oxygen Level Dependent (BOLD) signal. Systemic Low Frequency Oscillations (sLFO) are BOLD signals between 0.01 and 0.1 Hz originating from systemic physiological processes. While sLFO signals in the brain have been shown to travel with blood in numerous studies, their behavior in the spinal cord (SC) remains unexplored. This study characterizes the coupling between brain‐sLFO and SC‐sLFO signals. Understanding brain‐SC‐coupling is pivotal for unraveling the vascular continuity of the central nervous system, which plays a crucial role in SC‐injury pathophysiology. BOLD signal extraction involved registering structural masks to fMRI space to obtain average time series from the brain, SC, and superior sagittal sinus. The sLFOs of the time series were cross‐correlated to determine vascular delays and analyzed for band power. It is found that the SC‐sLFO signal comprises two components relative to the brain, showing opposite correlation polarity and varying delays. These findings suggest that highly oxygenated blood arrives at the spinal cord before arriving at the brain, and some component of the brain's venous output circulates to or near to the spinal cord later, likely due to unique arterial and venous pathways connecting the central nervous system. This insight offers a valuable imaging marker for future studies on the effects of SC injury on brain‐SC interconnectivity.

Abstract Objectives/Background Post‐traumatic headache (PTH) is a common symptom following mild traumatic brain injury (mTBI). Currently, there is no identified way to accurately predict if, when, and at what pace a person will have PTH improvement. In our prior studies, we focused on predicting headache improvement at 3 months post‐mTBI. However, that approach may overlook individual differences in how headaches evolve over time. This study aimed to identify individual subgroups based on their headache trajectories and to develop machine‐learning (ML) models for early prediction of headache evolution. Methods Participants with acute PTH completed a daily electronic headache diary over 3 months, recording their headache‐related symptoms. Tensor decomposition was utilized to extract latent factors underlying the time‐varying symptoms. We applied clustering techniques on the latent factors to identify patient subgroups with varying headache improvement trajectory. Next, we developed an ML method to classify each individual into a headache trajectory subgroup as early as possible within the 3‐month interval. Results Seventy‐three individuals with acute PTH (mean age = 44.8 years, SD = 14.0; 50 females/23 males) were enrolled between 0 and 59 days post‐mTBI. Data from 54 individuals were used as the training cohort for model training, and 19 individuals were used as the test cohort for model evaluation. Tensor decomposition extracted two latent factors: one factor representing the overall state of PTH severity and disability and the other representing the improvement state of these symptoms over 3 months. Clustering identified four patient subgroups with distinct headache evolution trajectories: (1) severe symptoms without improvement, (2) severe symptoms with mild improvement, (3) milder symptoms with substantial improvement, and (4) mildest symptoms with mild improvement. The proposed ML model achieved 0.80 cross‐validation accuracy in classifying individuals with PTH into subgroups for the training cohort and 0.84 accuracy for the test cohort. Notably, the model required only the first 2 weeks of headache data to accurately identify the subgroup with the mildest headaches, 3 additional weeks to identify the subgroup with the most severe headaches and no improvement in 3 months, and 2 additional weeks to distinguish the remaining subgroups. Conclusion This study identified subgroups of individuals with acute PTH with distinct headache improvement trajectories. The proposed ML method accurately classified individuals into these subgroups using the minimally necessary early headache data for each person, including detecting the subgroup with the mildest headaches at 2 weeks. This approach could offer an estimated forecast of headache burden over time and could assist clinicians with determining treatment needs and eligibility for PTH clinical trials.

Background Headache is a common symptom following mild traumatic brain injury (mTBI). Post-traumatic headache (PTH), a secondary headache disorder that develops after mTBI, often persists for months or years. To identify potential recovery mechanisms and prognostic biomarkers, the present study investigated whether longitudinal changes in pain-induced brain activation differ between healthy controls (HC) and PTH participants showing headache improvement and those without improvement. Methods Thirty-three participants who met International Classification of Headache Disorders, 3rd edition, criteria for acute PTH within 59 days post-mTBI and 33 HC participants were included with no significant differences in demographics. All participants underwent functional magnetic resonance imaging scans at baseline, four weeks, and 16 weeks post-enrollment using a thermal stimulation paradigm with noxious and non-painful heat stimuli. ‘Painful vs. Non-Painful Heat’ contrasts were generated using SPM12. PTH improvement was assessed at three months post-enrollment via electronic headache diaries. Two-sample t -tests compared the brain activation between HC and PTH at baseline. Linear mixed-effects models examined longitudinal changes for HC, PTH improvement and non-improvement groups across visits. Generalized linear models compared these groups within visits. Results Baseline analysis revealed several regions with significantly higher activation in acute PTH compared to HC, including bilateral postcentral gyrus, right superior temporal gyrus, right middle temporal gyrus, left inferior parietal gyrus, right superior parietal gyrus, left ventral striatum, left olfactory cortex, left gyrus rectus, and left middle occipital gyrus. Over time, the PTH improvement group demonstrated progressive normalization across all identified brain regions, whereas the non-improvement group showed only partial normalization in left ventral striatum, left olfactory cortex, and left gyrus rectus. Sustained elevated activation in specific regions distinguished PTH participants without headache improvement from those with headache improvement, suggesting potential biomarkers for persistent PTH. Conclusions Our findings demonstrate significantly altered pain-induced brain activations in participants with acute PTH compared to HC. Longitudinal analysis revealed distinct recovery trajectories: progressive normalization in the improvement group versus persistent alterations in the non-improvement group. These neuroimaging patterns may serve as biomarkers for identifying individuals at risk for persistent PTH, with implications for early intervention and personalized treatment approaches.

Abstract Background: Leukocyte immunoglobulin-like receptor B2 (LILRB2) suppresses immune cell activation, particularly within myeloid cells in the tumor microenvironment (TME), while the PD-1/PD-L1 axis serves as a key immune checkpoint that inhibits T-cell function. SPX-303 is a novel bispecific antibody designed to simultaneously block LILRB2 and PD-L1, thereby revitalizing antitumor immune responses. Here, we present initial findings from the ongoing first-in-human Phase 1 trial of SPX-303 in patients with advanced solid tumors, including safety, pharmacokinetics (PK), and receptor occupancy (RO). Methods: This is an open-label, multicenter Phase 1 study for patients with advanced solid malignancies with 3+3 dose-escalation design, followed by an expansion cohort at the recommended Phase 2 dose (RP2D). SPX-303 is administered intravenously every three weeks and safety is assessed through CTCAE v5.0 criteria. Primary Objectives of this study are to determine the safety, tolerability, and RP2D of SPX-303. Secondary endpoints include antitumor activity as well as characterization of the PK and PD of SPX-303. This study is currently open and enrolling in escalation cohorts. Citation Format: Justin Moser, Hao Xie, Yujie Zhao, Yousef Zakharia, Dongdong Li, Brandon William, Dinh-Duc Nguyen, Jack Hovey, Tiffany Li, Robert Cai, Jichun Ma, Jingdong Qin, Martin Siekierzycki, Anthony Haight, Hua Jin, Weiwei Mao, Kevin Bin Li, Gui-Dong Zhu. A first-in-human phase 1 study on the safety, PK, receptor occupancy, and pharmacodynamic markers of SPX-303, a first-in-class LILRB2×PD-L1 bispecific antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT116.

Abstract Gastrostomy tubes provide essential long-term enteral nutritional support for trauma patients unable to tolerate oral intake or if prohibited due to associated injuries. This review aims to explore the indications and special considerations unique to gastrostomy tube placement and management for patients following trauma. The specific special considerations addressed in this article are timing of gastrostomy tube placement, timing of gastric tube feeding, technique, indications for postpyloric feeding tubes, concomitant corticosteroid use, safety in patients with an open abdomen, overcoming an inability to pass a nasogastric tube, and considerations for postgastrostomy tube management.

ABSTRACTBackground and AimsOne strategy to minimize the risk of posttransplant lymphoproliferative disorder (PTLD) is to avoid an Epstein–Barr Virus (EBV) mismatch through kidney paired donation. We aimed to estimate the incidence of PTLD in EBV‐negative kidney transplant recipients with EBV‐positive donors (D+/R−) and evaluate the excess risk of death following the occurrence of PTLD.MethodsWe included adult patients in OPTN database who underwent kidney transplants between 2012 and 2022. Cox regression analysis was employed to evaluate the impact of EBV serostatus on the development of PTLD, and to assess mortality following PTLD diagnosis in D+/R− individuals.ResultsA total of 179 068 patients were included, with 92.8% in the R+, 6.4% in the D+/R−, and 0.8% in the D−/R− group. D+/R− exhibited a significantly higher risk of PTLD compared to R+ and D−/R− groups. D+/R− had a greater risk of PTLD when compared to D−/R− recipients (aHR: 3.82; p < 0.001). Among D+/R− recipients, those who developed PTLD had a significantly higher risk of mortality (aHR: 2.28; p < 0.001 in deceased donor kidney transplant [DDKT] and aHR: 5.22; p < 0.001 in living donor kidney transplant [LDKT]).ConclusionsD+/R− recipients have nearly a fourfold higher risk of PTLD compared to D−/R− recipients, suggesting that choosing an EBV D−/R− transplant could reduce the PTLD risk by about 73%. This data is crucial for counseling EBV‐negative patients considering kidney paired donation to avoid an EBV serostatus mismatch.