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A CASE OF FIBRILLARY GLOMERULONEPHRITIS ASSOCIATED WITH PEMBROLIZUMAB USE DURING BREAST CANCER TREATMENT
No full textPrior studies have enumerated various immune-mediated effects of which 1-2% involve the kidneys, starting from 10 days of initiation up to 3 months after discontinuation. AIN is the most common picture, although other pathologies like ATN, MCD, IgA nephropathy, FSGS, crescenteric GN, anti-GBM GN, C3 GN and ANCA-associated vasculitis have also been demonstrated. 4 cases of fibrillary glomerulonephritis (FGN) were ascribed to nivolumab, ipilimumab and atezolizumab, however, this report possibly describes the first occurrence related to pembrolizumab. A 73-year-old Caucasian female, with no history of CKD or proteinuria, was treated for invasive ductal carcinoma with pembrolizumab, doxorubicin and cyclophosphamide. Within 3-4 days of completing the 3rd cycle, she developed new-onset hypertension, with a corresponding creatinine rise from 0.94 to 2.05 mg/dL in 1 month and urine Alb/Cr ratio of 8253.8 mg/g. Renal biopsy revealed fibrillary glomerulopathy with moderate interstitial fibrosis and tubular atrophy. The only remarkable immunologic workup was a positive ANA. Creatinine appeared to improve initially with a prednisone taper over 5 months but eventually progressed to 2 mg/dL in 2 years. At 1 year, empagliflozin was added to stabilize proteinuria successfully. FGN is an infrequent renal disease with characteristic disorderly fibrils on microscopy. Although the exact mechanism remains unascertained, it has been linked to multiple malignancies including 5 cases of breast cancer. Higher age, creatinine and proteinuria worsen the prognosis with nearly 50% progressing to ESRD within 4 years, despite steroids and cytotoxic agents. In this case, FGN could reasonably correlate with both breast cancer and pembrolizumab use. However, the timing of disease onset in the setting of cancer remission favors the latter. In summary, considering the novelty of immune checkpoint inhibitors, an AKI attributable to their use demands early recognition to avoid potentially inappropriate treatment and grave consequences. Multicenter controlled trials can further uncover therapeutic options to prevent FGN progression
TCT-449 Automated SYNTAX Score Prediction Using Deep Learning Outperforms Expert Readers in Coronary Angiography Assessment
No full textBackground: SYNTAX score calculation remains subjective and time-consuming despite its critical role in revascularization decisions. We developed an automated deep learning system for end-to-end SYNTAX score prediction from multi-view coronary angiography. Methods: DeepCORO-CLIP (pretrained on 169,000 video-text pairs, Montreal Heart Institute 2017-2024) was fine-tuned on CardioSyntax dataset (1,844 patients, multi-view angiograms) to predict continuous SYNTAX scores (global/left/right). Split: 1,475 training, 369 test. Six interventionalists annotated exams using majority voting, categorizing: no disease (SYNTAX=0), mild (\u3c18), moderate (18-27), severe (\u3e27). AI outputs recategorized using optimized thresholds (≤2.23, 2.23-18.50, 18.50-22.95, \u3e22.95). Metrics: Pearson correlation, Cohen\u27s kappa, accuracy. Results: AI achieved strong correlations with ground truth SYNTAX scores (Pearson r=0.824 global, 0.795 left, 0.781 right). AI\u27s categorical agreement (κ=0.558) significantly outperformed human raters (κ=0.478; p\u3c0.001) and majority voting (73.8% accuracy vs 67.0% accuracy, p\u3c0.001). Overall accuracy: AI 73.8% vs individual raters 65.9%, 66.5%, 55.9%. By severity, AI achieved 83.6% for no disease, 65.6% mild, 45.0% moderate, 67.0% severe. [Formula presented] Conclusion: Deep learning SYNTAX prediction achieved physician-level performance with statistically significant superiority over individual raters and majority voting. Notably, for moderate disease (SYNTAX 18-27) where clinical stake making for revascularisation is highest, AI achieved 45.0% accuracy, highlighting potential to standardize assessment in this challenging category. Categories: CORONARY: Artificial Intelligence: Coronar
Risk Factors Associated with Longer Hospital Stay in Elderly Patients with Respiratory Syncytial Virus Infections
No full textBackground. Annually, 3-7% of healthy older patients and 4-10% of high-risk adults develop respiratory syncytial virus (RSV) infections. Elderly patients above 65 years of age, with congestive heart failure, chronic lung disease, or weakened immune systems are at high risk for severe RSV infections. Little is known about the factors that are associated with the length of hospital stay (LOS) among these elderly individuals. Methods. A multicenter historical cohort study was conducted on elderly patients ( \u3e65 years of age) hospitalized for laboratory-confirmed RSV-related diseases in Ascension hospitals in Southeast Michigan between January 2017 and December 2022. Hospitalized patients were identified using ICD 10 codes for RSV-related diseases. Electronic medical records were reviewed after IRB approval. LOS was categorized as below the mean LOS or at the mean and above. Data were analyzed using Student\u27s t-test, the chi-Squared test, the Mann-Whitney U test and logistic regression using SPSS v. 29.0. Results. Of 239 patients, the mean (sd) age of the cohort was 78.3 + 8.4 years, 157 (65.7%) were female and 176 (73.6%) were white. The mean body mass index (BMI) was 29.5 + 8.8 kg/m2. The mean Charlson Weighted Index of Comorbidity (CWIC) score was 2.4 + 2.0. The mean hospital LOS was 7.5 + 5.1 days. Prolonged LOS was noted in 89 (37.2%) patients. Factors associated with longer LOS ( \u3e7.5) in univariable analysis were chronic lung disease, solid tumors, CWIC score, smoking status, home oxygen, oxygen requirement during hospitalization, qSOFA, abnormal admission chest x-ray (CXR), lower respiratory tract infection, and respiratory failure requiring intubation. The multivariable logistic regression revealed that predictors for prolonged LOS among elderly patients were smoking status (OR, 2.2; 95% CI 1.2-4.0), abnormal admission CXR (OR, 2.1; 95% CI 1.2-3.7), and respiratory failure requiring intubation (OR, 9.4; 95% CI 2.6-34.4). Conclusion. Our study finds that patient\u27s smoking status, abnormal admission CXR and respiratory failure requiring intubation were significantly associated with prolonged LOS among elderly patients with RSV infections. Knowing these risk factors may help identify patients who would benefit from early interventions to mitigate the duration of hospitalization
Treatment and outcomes of breast cancer with leptomeningeal disease: Real-world experience in the African American population
No full textBackground: Leptomeningeal disease (LMD) is a rare but devastating complication of malignancies, affecting up to 5% of breast cancer patients. Survival is poor, typically 4-5 months despite aggressive treatment. While the literature on LMD is limited, data on the African American (AA) population are even more scarce. This study examines clinical characteristics and outcomes of breast cancer patients with LMD, with a focus on AAs. Methods: We retrospectively reviewed breast cancer patients diagnosed with LMD at Henry Ford Health (August 2014–August 2024). LMD diagnosis followed ESMO criteria, and treatment responses were assessed using modified RANO-LM criteria. Results: Forty-one patients were identified (18 Caucasian, 17 AA, 6 others), with a median age of 52 at diagnosis. Hormone receptor (HR)- positive tumors were most common (46%), followed by HER2-positive and triple-negative (27% each). Most had invasive ductal histology (71%) and grade 3 tumors (32%), with 51% presenting with de novo stage IV disease. Among AAs, the median age at diagnosis was also 52; receptor subtypes were HER2-positive (29%), HR-positive (35%), and triple-negative (35%). A higher proportion of AAs had a better performance status (ECOG 1) compared to the overall cohort (44% vs 24%). 34% of all patients received intrathecal (IT) therapy, most commonly with methotrexate. HER2-positive patients received the most IT treatments (median: 23). Systemic therapy (received by 49%) frequently included capecitabine, while 49% underwent CNS radiation. AAs had lower rates of IT therapy (29%), systemic therapy (47%), and CNS radiation (41%). Among all, overall response and disease control rates were 15% and 34%, respectively. For AAs, these rates were slightly better at 24% and 41%. Median event-free survival (EFS) was 2.2 months for both the overall and AA populations. Median overall survival (OS) was similarly poor: 1.8 months overall, and 2.2 months in AAs. Among receptor subtypes, HER2-positive patients had better EFS (7.1 months), and OS (3.4 months) among all, though that difference was not seen in AAs (median not evaluable). Poor performance status predicted worse EFS and OS across all groups. Other factors, including histology, grade, stage at diagnosis, time to onset of LMD, concurrent parenchymal metastases, and metastatic burden, showed no significant impact on EFS and OS in the overall cohort or the AA subgroup. Conclusions: Our study highlights clinical differences between the AA population and the general cohort, particularly in receptor status, performance status, and treatment patterns. Although AAs had numerically better response rates, survival outcomes were similar in both groups. The aggressive nature of LMD underscores the limited effectiveness of available therapies, with few patients able to receive or benefit from multimodality treatment
Association of Preinjury Beta-Blocker Exposure With Brain Injury Biomarkers Following Traumatic Brain Injury
No full textOBJECTIVE: Beta-blockers have been studied for their impact on traumatic brain injury (TBI). We aimed to examine the association of preinjury beta-blocker exposure with early brain injury biomarker levels and outcomes following TBI.
METHODS: We retrospectively studied adults (≥40 y) participating in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. The exposure was preinjury beta-blocker utilization. Primary outcome was blood-based brain injury biomarker levels on day 1 following injury. Secondary outcomes included biomarkers on days 3 and 5, hospital mortality, and the 6-month Glasgow Outcome Scale-Extended. Inverse probability-weighted models assessed the association between preinjury beta-blocker exposure, biomarker levels, and outcomes, stratified by TBI severity.
RESULTS: A total of 1185 patients were included, with 101 on preinjury beta-blockers (BB+): 21 in the moderate/severe group and 80 in the mild TBI group. BB+patients were older than BB- in both mild (67 vs. 57 y, P\u3c 0.001) and moderate/severe TBI (64 vs. 56 y, P=0.003). Hypertension was more common in BB+patients (78% mild, 67% moderate/severe, P\u3c 0.001). Preinjury beta-blocker use was not associated with day 1 biomarker levels. The 6-month GOSE scores in the BB+ moderate/severe TBI were lower, but the effect was marginal (B= -1.20, 95% CI: -2.39 to -0.01, P=0.049).
CONCLUSION: Our study did not find a clear association between preinjury beta-blocker exposure and day 1 blood-based brain injury biomarkers or clinical outcomes. These findings warrant confirmation in future studies with larger cohorts
Adaptive deep brain stimulation targeting the subthalamic nucleus in a patient with Parkinson\u27s disease: A CARE compliant case report
No full textRATIONALE: Adaptive deep brain stimulation (aDBS) represents a notable advancement in treating Parkinson\u27s disease (PD), as it offers enhanced therapeutic outcomes and personalized management by adjusting stimulation parameters in real-time according to individual neural signals. This approach minimizes adverse effects commonly associated with standard continuous deep brain stimulation (cDBS). This case report describes the progress of a 62-year-old man with severe PD who demonstrated notable enhancement in motor symptoms and quality of life throughout a 3-month trial period using aDBS.
PATIENT CONCERNS: A 62-year-old man who has been suffering from Parkinson\u27s disease.
DIAGNOSES: The patient had been diagnosed with PD for 10 years. The patient\u27s motor symptoms, including dyskinesia during the on-state and akinesia during the off-state, progressively worsened over time.
INTERVENTIONS: The patient underwent bilateral subthalamic nuclei DBS surgery with cDBS. Following progressive worsening of motor symptoms, he was transitioned to aDBS.
OUTCOMES: The aDBS system adaptively modified stimulation parameters by utilizing real-time neural feedback from beta band activity detected in the subthalamic nucleus, resulting in decreased dyskinesia and reduced reliance on medication. The customized strategy led to a significant improvement in motor symptoms, a reduction in dyskinesia, and an overall enhancement in quality of life during the 3-month trial period.
LESSONS: Existing evidence highlights the ability of aDBS to improve motor control and reduce problems associated with DBS, such as speech and gait abnormalities. Research findings have demonstrated significant improvements in motor scores and a reduction in stimulation time, highlighting the effectiveness of aDBS and its ability to prolong the lifespan of devices
Preterm birth trends in the United States post aspirin recommendation guidelines
No full textOBJECTIVES: To evaluate changes in preterm birth (PTB) rates in the U.S. following the United States Preventive Services Task Force (USPSTF) aspirin recommendation guidelines.
METHODS: A retrospective cohort study was conducted using the US Natality database. The pre-aspirin (pre-ASA) group included births from 2010-2014, while the post-aspirin (post-ASA) group included births from 2016-2021. Births from 2015, the guideline publication year, were excluded. Outcomes were overall PTB rates (\u3c 37 weeks) and early PTB rates (\u3c 34 weeks). Univariable and multivariable analyses were performed. Projected trends based on 2010-2014 data were compared to observed trends post-guideline implementation to assess differences.
RESULTS: The pre-ASA group included 12.1 million births, and the post-ASA group included 17.6 million. Adjusted analyses showed lower PTB rates in the post-ASA group: \u3c 37 weeks (8.4 % vs 8.8 %; aOR 0.940 [0.937-0.944]) and \u3c 34 weeks (2.3 % vs 2.4 %; aOR 0.92 [0.910-0.923]). However, observed post-ASA trends closely followed projected trends until 2021, when PTB rates exceeded projections.
CONCLUSION: Although adjusted analyses suggest modest reductions in PTB following USPSTF aspirin guidelines, observed trends did not show a clear reduction following aspirin implementation
Adoption and perioperative outcomes of single-port (SP) robotic partial nephrectomy in the state of Michigan: a MUSIC-KIDNEY analysis
No full textRobotic partial nephrectomy (RPN) is a standard-of-care nephron-sparing intervention for clinical stage T1 renal masses (cT1RMs). We evaluated RPN outcomes performed using the da Vinci single port (SP) and multiport (Xi) platforms in a statewide quality improvement collaborative since SP introduction in Michigan. MUSIC-KIDNEY maintains a prospective registry of newly diagnosed cT1RM. Six surgeons from three practices within MUSIC have performed both. The perioperative data from patients undergoing SP and Xi RPN with these surgeons October 2020-August 2023 were analyzed. These surgeons completed a survey to assess reasons for choosing SP over Xi RPN. Of 828 RPNs performed by all MUSIC surgeons in the same duration, a total of 314 (38%) RPNs were completed by the six included surgeons who performed 121 (39%) RPNs with SP and 193 (61%) with Xi. SP RPN more commonly utilized the retroperitoneal approach than Xi RPN (80% vs. 6.1%, p \u3c 0.001). When comparing perioperative outcomes, the experienced SP surgeon utilized same-day (55% vs. 9.5% vs. 5.7%, p \u3c 0.001) and opioid-free discharge (77% vs. 22% vs. 18%, p \u3c 0.001) significantly more than other urologists for both SP and Xi cases without a significant increase in positive surgical margins, ED visits, or readmissions. The survey results showed that surgeons early in the learning curve for SP RPN prefer to use SP for smaller, less complex masses. Although there has been limited adoption of SP RPN, initial experiences with SP RPN demonstrate procedural safety comparable to Xi RPN. Both robotic systems provide advantages, with SP mainly facilitating the retroperitoneal approach
Long-term Cancer Control Outcomes After Robot-assisted Radical Prostatectomy in Pathologically Non-organ-confined High-risk Prostate Cancer: 20-year Report from a Single Tertiary Referral Center
No full textBACKGROUND AND OBJECTIVE: Exhaustive evidence on the long-term efficacy of robot-assisted laparoscopic prostatectomy (RALP) in non-organ-confined high-risk prostate cancer (PC) is still lacking. Our aim was to evaluate long-term oncological outcomes in this subset of patients treated with RALP at a single referral center.
METHODS: We included 803 patients with pathologically non-organ-confined high-risk PC (≥ pT3a and/or pN1) at RALP between 2001 and 2022 at Henry Ford Hospital (Detroit, MI, USA). All patient underwent RALP using the Vattikuti Institute technique, with or without extended pelvic lymph node dissection (external iliac, obturator, and internal iliac nodes). The Kaplan-Meier method was used to estimate overall survival (OS) and additional treatment-free survival. The probability of PC-specific survival (PCSS) was estimated via the competing-risks method. Competing-risk and Cox regression analyses were used to identify potential predictors of PC-specific mortality (PCSM), any-cause mortality (ACM), and additional treatment.
KEY FINDINGS AND LIMITATIONS: We included 803 patients, of whom 415 (51.5%) had pT3a, 385 (47.9%) had ≥ pT3b, 323 (40%) had pN1, and 670 (84%) had grade group 4-5 PC. Of the 635 patients with status information regarding additional treatment, 416 received further therapy after surgery. Specifically, 46, 110, and 260 underwent RT only, HT only, or RT + HT, respectively. Median follow-up was 72 mo (interquartile range 28-120). The 20-yr survival rates were 72.7% (95% confidence interval [CI] 56.8-86,5%) for PCSS and 45.2% (95% CI 29.1-60.1%) for OS. The rates of survival free from additional treatment were 31.3% (95% CI 26.1-36.5%) at 10 yr and 20.3% (95% CI 14.9-26.4%) at 15 yr. Multivariable regression revealed pT3b-4 stage as an independent predictor of PCSM (hazard ratio [HR] 2.50; p = 0.008), ACM (HR 1.84; p = 0.006), and additional treatment (HR 1.69; p \u3c 0.001).
CONCLUSIONS AND CLINICAL IMPLICATIONS: For patients with non-organ-confined high-risk PC, RALP achieves long-term oncological control. This study provides the longest follow-up after RALP as the primary local treatment for patients with truly aggressive PC forms and offers valuable insights for patient counseling on long-term outcomes
Once-Nightly Sodium Oxybate Meets American Academy of Sleep Medicine Criteria for Treatment of Narcolepsy
No full textData from the REST-ON trial were not available before the 2021 American Academy of Sleep Medicine (AASM) clinical practice guideline update, which included a literature review through August 2020. This post hoc analysis from REST-ON assessed participants who achieved clinically significant improvements on individual AASM clinical significance thresholds (CSTs). Composites of the coprimary endpoints and a secondary endpoint were also analysed. Participants with narcolepsy aged ≥ 16 years were randomised 1:1 to once-nightly sodium oxybate (ON-SXB) or placebo for 13 weeks. Coprimary endpoints were mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Improvement (CGI-I) rating, and number of cataplexy episodes; secondary endpoints included the Epworth Sleepiness Scale (ESS) score. Outcomes with ON-SXB treatment compared with baseline were assessed according to the CSTs, and for those who met CSTs, the proportions of participants who experienced clinically significant improvements on a composite of ≥ 2, ≥ 3, or 4 endpoints were calculated. For improvements from baseline with ON-SXB at Week 13 (9-g dose), mean sleep latency on the MWT increased 10.8 min (CST, ≥ 2-min increase), 92.8% rated improvement on the CGI-I (CST, ≥ 33% of participants reporting improvement), reduction in number of cataplexy episodes was 60.8% reduction (CST, ≥ 25% reduction), and reduction in ESS score was -6.5 (CST, ≥ 2-point decrease). At Weeks 3, 8 and 13, significantly more participants treated with ON-SXB versus placebo experienced clinical improvements on ≥ 2, ≥ 3, or 4 endpoints (p ≤ 0.05). These data demonstrate the robust efficacy of ON-SXB across multiple clinically important narcolepsy symptoms per established CSTs, further supporting the use of ON-SXB in clinical practice. Trial Registration: This manuscript presents the results of a post hoc analysis from the REST-ON clinical trial (NCT02720744)