Long-term Follow-up Of Patients Research Articles

Matrix-Assisted Autologous Chondrocyte Transplantation for the Treatment of Patellofemoral Chondral Lesions: Long-term Results at a Minimum 15-Year Follow-up.

A few studies have documented the long-term results of chondrocyte-based procedures for the treatment of patellofemoral cartilage lesions, but specific results are lacking after matrix-assisted autologous chondrocyte transplantation (MACT) for patellar and trochlear lesions. To document the clinical results of MACT for the treatment of patellar and trochlear chondral defects at long-term follow-up. Cohort study; Level of evidence, 3. A total of 44 patients were prospectively evaluated after MACT for patellofemoral lesions. There were 24 patients affected by patellar lesions, 16 by trochlear lesions, and 4 with both patellar and trochlear defects. Clinical outcomes were analyzed using the International Knee Documentation Committee (IKDC) subjective form, EuroQol visual analog scale, and Tegner score for sport activity level before surgery and at follow-up time points of 5, 10, and a minimum of 15 years (mean final follow-up, 17.6 ± 1.6 years). A Kaplan-Meier survival analysis was performed to examine the survival to failure. Failure was defined as the need for a second surgery because of the persistence of symptoms related to the primary defect. An overall significant improvement was documented from baseline to the last follow-up. The IKDC subjective score improved in the trochlear group from 41.0 ± 13.3 at baseline to 83.9 ± 21.6 at 5 years (P < .005), remaining stable up to the final follow-up (81.3 ± 20.5). In the patellar group, the IKDC subjective score improved from 36.1 ± 14.4 at baseline to 72.3 ± 17.5 at 5 years (P < .005), remaining stable up to the final follow-up (62.0 ± 20.3). Patients with trochlear lesions presented higher IKDC subjective scores compared with those with patellar lesions at 5 (P = .029), 10 (P = .023), and ≥15 years (P = .006) of follow-up. Similar trends were documented for the Tegner score, while no differences were documented for the EuroQol visual analog scale score between patellar and trochlear lesions. There were 4 failures (9.1%) during the follow-up period. The Kaplan-Meier survival analysis did not show statistically significant differences between trochlear and patellar lesions. This hyaluronic acid-based MACT technique offered positive and durable clinical outcomes with a low failure rate at long-term follow-up in patients affected by patellofemoral cartilage lesions. However, trochlear and patellar lesions demonstrated a notable difference in terms of clinical findings and sport activity level, with significantly higher results for patients with trochlear lesions but less satisfactory outcomes for patients with patellar lesions.

Long-Term Follow-Up of Patients with Chronic Kidney Disease: Renal Function Decline and Associated Risk Factors

ABSTRACT Evaluating the chronic course of chronic kidney disease (CKD) and identifying associated risk factors is essential for effective management. This study aims to identify risk factors and monitor the decline in renal function through prolonged follow-up of CKD patients. This retrospective cohort study included 410 CKD patients diagnosed between 2015 and 2022. Data collected included demographics, comorbidities, and repeated measurements of glomerular filtration rate (GFR) and proteinuria. Statistical analyses examined the association between GFR decline and risk factors such as age, diabetes, hypertension, and proteinuria during the follow-up period. The cohort showed a progressive decline in GFR over time. Significant associations were found between GFR decline and age, diabetes, hypertension, and higher proteinuria levels (P &lt; 0.001). Age was associated with a 0.32 ml/min decline in GFR per 1.73 m², while the coefficients for hypertension and diabetes were -2.98 and -4.21, respectively. A strong correlation was found between proteinuria and GFR decline (β = -6.78, P &lt; 0.001). Early identification and management of risk factors are crucial for slowing CKD progression. These findings underscore the need for targeted interventions to preserve renal function and improve patient outcomes.

Retrospective Review of Tonsillectomy and Adenoidectomy Outcomes in Pediatric Patients: Complications and Recurrence Rates

ABSTRACT Objective: This retrospective review aimed to analyze the outcomes of tonsillectomy and adenoidectomy (T and A) procedures in pediatric patients, focusing on complications and recurrence rates. Methods: Medical records of pediatric patients who underwent T and A were retrospectively reviewed. Data on patient demographics, preoperative indications, surgical techniques, intraoperative findings, postoperative complications, and recurrence rates were collected and analyzed. Results: A total of 240 pediatric patients were included in the study. Postoperative complications occurred with postoperative bleeding being the most common (5.2%). Other complications included infection (3.1%), respiratory compromise (1.7%), and velopharyngeal insufficiency (0.6%). Recurrence of tonsillitis and adenoiditis was observed in 6.7% of cases, respectively. Conclusion: This retrospective review provides valuable insights into the outcomes of T and A procedures in pediatric patients. Postoperative complications, including bleeding and infection, underscore the importance of meticulous surgical technique and postoperative care. Recurrence rates of tonsillitis and adenoiditis highlight the need for long-term follow-up and surveillance in pediatric patients undergoing T and A.

Long-term follow-up in congenital diaphragmatic hernia

With improvements in initial care for patients with congenital diaphragmatic hernia (CDH), the number of CDH patients with severe disease who are surviving to discharge has increased. This growing population of patients faces a unique set of long-term challenges, multisystem adverse outcomes, and post-intervention complications requiring specialized multidisciplinary follow-up. Early identification and intervention are essential to mitigate the potential morbidity associated with these challenges. This manuscript outlines a general framework for long-term follow-up for the CDH patient, including cardiopulmonary, gastrointestinal, neurodevelopmental, surgical, and quality of life outcomes.

Electrocardiographic abnormalities and NT-proBNP levels at long-term follow-up of patients with dyspnea after pulmonary embolism

ABSTRACTS Objectives Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. Design All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. Results Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. Conclusions We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Long-Term Follow-Up of Patients with Advanced Colorectal Liver Metastasis: A Survival Analysis from the Randomized Controlled Multicenter Trial LIGRO.

The objective of this study was to evaluate the long-term oncological outcomes of patients with colorectal liver metastasis (CRLM) randomized for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). For advanced CRLM, TSH or ALPPS may be needed for tumor freedom. The randomized, controlled, multicenter trial LIGRO showed an increased resection rate in patients who underwent ALPPS but no difference in morbidity or mortality. The 2-year survival analysis revealed better overall survival in the ALPPS group. Here, the long-term survival analysis from the LIGRO trial is reported. In the LIGRO trial, 100 patients were randomized to TSH or ALPPS, with the option of rescue ALPPS if insufficient growth was found after the initial step of TSH. Patients were enrolled between June 2014 and August 2016. Follow-up data for this study were collected between November 2022 and February 2023. In total, 16 patients were alive at the end of the follow-up period. The estimated median follow-up time was 93 months. Estimated median overall survival times were 45 months in the ALPPS group and 27 months in the TSH group (P = 0.057), with 5-year survival rates of 31% and 20%, respectively. Positive prognostic factors were liver tumor-free status at the first follow-up and rectal primary tumor. Negative prognostic factors were extrahepatic disease and increasing CLRM size. Liver tumor-free status is a predictor of long-term survival, along with extrahepatic disease, large CRLM size, and rectal primary tumor. Survival did not significantly differ between patients treated with ALPPS or TSH.

LGG-32. MALIGNANT TRANSFORMATION OF PEDIATRIC LOW-GRADE GLIOMA TO SECONDARY HIGH-GRADE GLIOMA - REPORT FROM THE GERMAN BRAIN TUMOR STUDIES

Abstract BACKGROUND Malignant transformation (MT) of pediatric low-grade glioma (pLGG) to secondary high-grade glioma (sHGG) is a rare but momentous event. We explored its clinical, epidemiologic, and molecular characteristics and risk factors. METHODS Forty-eight pediatric patients with histology-based or radiological (n=4) diagnosis of primary LGG (median age 10.2 years [range, 0.7–16.9]) and subsequent sHGG were identified within registries of the HIT-network from 1996-2019. For 29 patients, tumor specimens of both pLGG and corresponding sHGG were available for neuropathological review and studied genetically. RESULTS MT occurred after median 4 years (range, 0.5-14) following LGG diagnosis. Its 15-year cumulative incidence was 1.6±0.4% (23/1586 SIOP-LGG-2004 patients), but 11.7±4.1% (9/100) for diffuse pLGG WHO-grade 2 (DG2). Clinical risk factors for MT were spinal location and prior dissemination. MT was accompanied by an increment of nuclear p53 accumulation (20/29 tumors), cytogenetic and molecular alterations. CDKN2A/B homozygous deletions (7/12 tumors), 1p/1q alterations (4/12) and ATRX loss (3/12) were the most common acquired alterations detected in sHGG. 8/16 tumors were unclassifiable by methylation profiling. DG2s (n=19), harboring IDH-1 mutation in 3/9 cases, progressed to diffuse WHO-grade 3 (n=8) or grade 4 HGG (n=9), two developed gliomatosis cerebri. Circumscribed LGG (PA, n=13; GG, n=7; PXA, n=4; DNET, n=1) typically harbored MAPK/ERK pathway alterations (BRAF-/NTRK-/FGFR-fusions, n=5/9; BRAFV600E mutation, n=4/12) and transformed to non-diffuse HGG (n=14), but also to diffuse grade 4 HGG. H3 K27M-/BRAFV600E co-mutation in two of these patients eventually resulted in MT to fatal diffuse midline glioma. Thirty-five sHGG patients received radio-chemotherapy. Overall survival at 5 and 10 years following MT was 49±8% and 31±8%. CONCLUSIONS Our findings underline the importance of careful long-term follow-up of patients with pLGG. Repeated resection/biopsy of recurrent/progressing or “atypical” tumors should be pursued and include molecular typing to identify patients at risk for MT and initiate appropriate treatment.

Bipolar disorder. IV: Early suicide attempts in a long-term follow-up of patients with bipolar disorder

BackgroundBipolar disorder (BD) is a serious chronic disease with a high frequency of suicide attempts (SA) and suicides. There are few long-term studies concerning characteristics of SA in BD, especially what characterizes early from late SA. MethodsA long-term study of 51 BD patients (DSM-IV) with SA were collected from lithium dispensaries in northern Sweden. Patients were divided into early SA (the first five years) after age of onset (AOO) or late SA. ResultsPatients with early SA were younger (p = 0.036), met BD earlier (p = 0.005), had less repeated depressions before SA (p = 0.002), often performed SA at first episode (p < 0.001) and before initiating of lithium (p = 0.002). Before first SA they had, fewer but more frequent episodes/year (p < 0.001), fewer depressive (p < 0.001) but more frequent depressive episodes/year (p < 0.001), lower frequency of hypomanic (p = 0.016) or manic episodes (p = 0.006). They had a higher frequency of episodes/year off (p = 0.047) and on (p = 0.042) lithium. Twenty percent of all patients performed SA at first episode, 47 % early SA and 65 % first ten years after AOO.Early SA was associated with a family history of first- and/or second-degree relative of affective disorder (AD) (p = 0.005), first-degree relative of AD (p = 0.031) and first-degree relative of BD (p = 0.049). All patients with early SA had a family history of AD. ConclusionsPatients with early SA have a more severe form of BD. Family history of AD among first- and/or second-degree relatives is significantly associated with especially early SA which implies a special psychiatric treatment and care for this BD group.

Long term follow-up of patients with patent ductus arteriosus after transcatheter closure.

To investigate the concurrent, long-term, and future adverse events and assess the trend of adverse events in pediatric patients with patent ductus arteriosus (PDA) after transcatheter closure. A total of 1590 patients underwent transcatheter PDA closure were enrolled, including 465 patients (median age = 22 months) in the training group and 1125 patients in the validation group. Logistic regression analysis was used to assess independent risk factors associated with concurrent adverse events after closure. The chi-square test was used to evaluate the 5-year follow-up trend. Multivariable logistic regression analysis indicated that low age, female, and high pulmonary end diameter were independent risk factors for concurrent adverse events after closure. For patients without concurrent adverse events and for those who with concurrent adverse events but return to normal, the Chi-square test showed no abnormal results at the 5-year follow-up. Furthermore, the follow-up data of the validation group were not significantly different from those of the training group. The value of long-term follow-up of children may be limited for those who did not have a concurrent adverse event after closure nor for those who had a concurrent adverse event after closure but returned to normal during the 5-year follow-up period. Follow-up monitoring of adverse events tended to be recommended in pediatric patients with PDA after transcatheter closure. However, follow-up in these pediatric patients is expensive and there is a risk of sedation for echocardiography examination frequently. ·Patients who had no concurrent adverse events after closure did not show any abnormality at 5-year follow-up. ·Most of the patients who had concurrent adverse events after closure returned to normal at 5-year follow-up. The value of long-term follow-up may be limited for the above patients after transcatheter PDA closure.

CDKL5 deficiency-related neurodevelopmental disorders: a multi-center cohort study in Italy

CDKL5 deficiency disorder (CDD) is a complex clinical condition resulting from non-functional or absent CDKL5 protein, a serine–threonine kinase pivotal for neural maturation and synaptogenesis. The disorder manifests primarily as developmental epileptic encephalopathy, with associated neurological phenotypes, such as hypotonia, movement disorders, visual impairment, and gastrointestinal issues. Its prevalence is estimated at 1 in 40,000–60,000 live births, and it is more prevalent in females due to the lethality of germline mutations in males during fetal development. This Italian multi-center observational study focused on 34 patients with CDKL5-related epileptic encephalopathy, aiming to enhance the understanding of the clinical and molecular aspects of CDD. The study, conducted across 14 pediatric neurology tertiary care centers in Italy, covered various aspects, including phenotypic presentations, seizure types, EEG patterns, treatments, neuroimaging findings, severity of psychomotor delay, and variant-phenotype correlations. The results highlighted the heterogeneity of seizure patterns, with hypermotor-tonic-spasms sequence seizures (HTSS) noted in 17.6% of patients. The study revealed a lack of clear genotype–phenotype correlation within the cohort. The presence of HTSS or HTSS-like at onset resulted a negative prognostic factor for the presence of daily seizures at long-term follow-up in CDD patients. Despite extensive polypharmacotherapy, including medications such as valproic acid, clobazam, cannabidiol, and others, sustained seizure freedom proved elusive, affirming the inherent drug-resistant nature of CDD. The findings underscored the need for further research to explore response rates to different treatments and the potential role of non-pharmacological interventions in managing this challenging disorder.

Long-term follow-up of patients treated with laser balloon for atrial fibrillation: A high volume center experience with the first- and second-generation laser balloon.

Laser balloon (LB) pulmonary vein isolation (PVI) is an established ablation technique for atrial fibrillation (AF). We report long-term follow-up and procedural data of LB-PVI and we compare the first and second LB generation. Patients undergoing LB ablation with first- (LB1) or second-generation LB (LB2) for AF were retrospectively enrolled and divided into two groups. Procedural endpoint was complete PVI. Clinical success was defined as no recurrence of AF/atrial tachycardia after a 90 days blanking period. 538 patients were included (age 66 ± 10 years, 58% paroxysmal AF), 427 in LB1 and 111 in LB2. 2079 PVs were targeted and 2073 (99.7%) were successfully isolated; 2027 (97.5%) using solely the LB. Additional touch-up ablation was limited (46 PVs; 2.2%) with no difference between the groups. Procedural (LB1: 120 ± 33 minutes vs. LB2: 99 ± 22 min; p < .001) and fluoroscopy time (LB1: 11.2 ± 5 min vs. LB2: 8.5 ± 3 min; p < .001) were shorter with LB2. The complication rate was 8.9% (LB1: 10.1% vs. LB2: 4.5%; p = .067) with most complications resulting from the access site (21/48). Overall freedom from AF after 1-year was 73.7% (paroxysmal AF: 76.9%; persistent AF: 69.3%; p < .001) with no difference between the groups (LB1: 73.4% vs. LB2: 74.7%; p = .491). LB showed a high efficacy and acceptable safety, with numerically lower complication rates with the second-generation LB. Procedure and fluoroscopy times were shorter with LB2. Overall, 73.7% of patients were free from AF at 1-year, with comparable results among both generations.

Breast cancer orbital metastases: Clinical, histopathological features and disease related survival in a retrospective case series

PurposeTo analyze the clinical, radiological and histopathological features, and long-term follow-up of patients with orbital metastases originating from a primary breast carcinoma. Main outcomes were: demographic characteristics of the population, clinical ophthalmological presentation, histological features, orbital metastasis latency, disease related survival, mortality rate. DesignA retrospective observational case-series. MethodsThe medical records of 10 female patients affected by orbital metastases originating from a primary breast carcinoma referring at our tertiary referral center from 01/2016 to 12/2023, were reviewed. ResultsThe median age was 63 (71.50 - 57.25) years (time of orbital biopsy). The prevalent histotype of orbital metastases of breast cancer was lobular 9.00 (90 %). The median orbital metastasis latency time in months was 9 months (IQR: 11 - 5) (in one case the orbital metastases were the first manifestation of an unknown primary tumor). The median Disease Related Survival (DRS) during the observation period was 17.50 months and the 24 months survival rate 57.14 %. The overall Mortality Rate in our population was 60 %. ConclusionsThe most frequent histotype of breast cancer orbital metastasis is the lobular one. The primary tumor precedes the onset of orbital metastasis in the majority of cases and tends to present with the classic symptoms of a mass occupying and infiltrating space. Orbital metastases are a sign that the disease is at an advanced stage, the mortality rate is high and DRS low.

Long-term outcomes following paclitaxel-coated balloons versus thin-strut drug-eluting stents for treatment of in-stent restenosis in chronic coronary syndrome (CCS Dragon-Registry).

The long-term outcomes for patients with in-stent restenosis (ISR) presenting with chronic coronary syndrome (CCS) are not well studied. We aimed to investigate the outcomes for patients with drug-eluting stents (DES)-ISR and CCS undergoing percutaneous coronary intervention (PCI) with drug-coated balloons (DCB) or thin strut-DES. A total of 846 consecutive patients from the Dragon-Registry with CCS and DES-ISR who underwent PCI with thin (strut thickness <100 μm) strut-DES (381 [45%]) or paclitaxel-DCB (465 [55%]) for DES-ISR were enrolled between February 2008 and October 2021. The median follow-up was 1006 (IQR 426-1770) days. The primary outcome was target lesion revascularization (TLR). Secondary outcomes were target vessel revascularization (TVR) and device-oriented composite endpoint (DOCE: cardiac death, TLR, or target vessel myocardial infarction [TV-MI]). Patients who received DES, compared with those who received DCB, had lower crude rates of TLR (hazard ratio [HR], 0.50 [95% CI, 0.34-0.74]; P <0.001), TVR (HR, 0.56 [95% CI, 0.39-0.86]; P <0.001), and DOCE (HR, 0.63 [95% CI, 0.45-0.88]; P = 0.007). The incidence of cardiac death and TV-MI were similar in both groups. After matching, the observed differences persisted in terms of TLR (HR, 0.54 [95% CI, 0.33-0.88]; P = 0.013), TVR (HR, 0.57 [95% CI, 0.41-0.80]; P = 0.009) and DOCE (HR, 0.65 [95% CI, 0.42-0.99]; P = 0.046) between the DES and DCB groups, respectively. In long-term follow-up of CCS patients undergoing PCI of ISR, the use of DES was associated with reduced rates of TLR, TVR, and DOCE compared with patients treated with DCB.

PET-CT 18F-PSMA 1007 in the staging of patients with prostate cancer prior to curative intent radiotherapy: a prospective observational study

Objective: The objective of our study was to assess whether there are staging changes in CaP with PET PSMA compared to standard diagnostic methods, and if these changes occurred, to understand how they altered the treatment of patients with an initial diagnosis of CaP and their relationship with the D'amico score. Methods: We present a prospective observational study conducted on patients initially diagnosed with prostate cancer, who underwent standard staging studies alongside PET PSMA imaging. Results: Forty patients diagnosed with prostate cancer were staged using standard diagnostic methods and PET PSMA. In 40% of the patients, initial staging changed based on the results obtained from PET PSMA. After PET PSMA, the uro-oncology committee decided to modify the initial treatment plan in 27.5% of the cases, including radiation boost targeting the extra-prostatic lesions detected by PET PSMA. When correlating the change in staging with PET PSMA versus the D'amico risk score, no changes were observed in the low-risk group, 19% in the intermediate-risk group, and 62% in the high-risk group. These differences were statistically significant (X2=9.2; df=2; p=0.01). Limitation and value: The study faced limitations in sample size and lack of long-term patient follow-up. However, it highlights key contributions: the promising evaluation of PET PSMA in staging, its influence on therapeutic decisions, and its association with the D'amico score. Conclusion: PET PSMA showed substantial changes in CaP staging, particularly in higher-risk patients, suggesting its potential utility in guiding therapeutic decisions before radiotherapy.

Long-term prognosis in patients with pulmonary embolism

Venous thromboembolism (VTE), clinically expressed as deep vein thrombosis (DVT) or pulmonary embolism (PE), is, globally, the third most common acute cardiovascular syndrome after myocardial infarction and stroke. Pulmonary embolism is associated with high morbidity and mortality. The long-term prognosis of these patients is insufficiently studied.Aim: To analyze mortality and clinical events at long-term follow-up in patients with confirmed PE. Material and methods: The study included 168 patients with PE, 53% men and 47% women, mean age 61.2±12.8 years, consecutively hospitalized in the Institute of Cardiology. Patients were classified into four risk groups according to the 2019 European Society of Cardiology Guidelines. Patients were followed-up for a mean period of 11.4±0.9 months. Results. During the study period died 23 people (13.7%), 8 of them during hospitalization and another 15 - after discharge from the hospital; in the latter, death occurred suddenly - in 4 cases (26.6%), it was due to cardiovascular causes- in 4 cases (26.6%), through cancer - in 5 (30%) people and from other causes - in 2 (13.3%) patients. Recurrent VTE was observed in 4 (2.5%) subjects, including PE - in 3 and DVT in 1 patient. During the surveillance period 4 (2.5%) patients developed stroke, 5 (3.1%) - acute myocardial infarction, 1 (0.2%) patient - another arterial event. Hemorrhagic complications suffered 20 patients. Chronic thromboembolic pulmonary hypertension was detected in 12.4% of people over 5.4±2.8 months after primary PE. Newly diagnosed cancer was observed in 2 (1.25%) people.Conclusions. The mortality rate in PE patients over an average period of 11.4±0.9 months was 13.7%, including 4.7% - in hospital and 8.9% - at long-term follow-up; in-hospital death was significantly higher in patients in the high and intermediate high risk category compared to those with intermediate-low and low risk and no statistically significant differences were established between these groups in the long-term mortality rate; the main cause of death in the hospital was PE, and during the surveillance period death from cardiovascular causes predominated, followed by death from cancer.

Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer.

Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer. A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data. Personalized Signatera assays detected ctDNA ahead of clinical or radiologic relapse in 30 of the 34 patients who relapsed (patient-level sensitivity of 88.2%). Relapse was predicted with a lead interval of up to 38 months (median, 10.5 months; range, 0-38 months), and ctDNA positivity was associated with shorter relapse-free survival (P < .0001) and overall survival (P < .0001). All relapsing triple-negative patients (n = 7/23) had a ctDNA-positive test within a median of 8 months (range, 0-19 months), while the 16 nonrelapsed patients with triple-negative breast cancer remained ctDNA-negative during a median follow-up of 58 months (range, 8-99 months). The four patients who had negative tests before relapse all had hormone receptor-positive (HR+) disease and conversely, five of the 122 nonrelapsed patients (all HR+) had an occasional positive test. Serial postoperative ctDNA assessment has strong prognostic value, provides a potential window for earlier therapeutic intervention, and may enable more effective monitoring than current clinical tests such as cancer antigen 15-3. Our study provides evidence that those with serially negative ctDNA tests have superior clinical outcomes, providing reassurance to patients with breast cancer. For select cases with HR+ disease, decisions about treatment management might require serial monitoring despite the ctDNA-positive result.

Long-term follow-up of patients with hairy cell leukemia treated with different modalities at a single institution: Real-life experience over 25 years.

e19023 Background: Hairy cell leukemia (HCL) is an uncommon and indolent leukemia of mature B cells, accounting for 2% of all lymphoid neoplasms. We analyzed characteristics, treatment modalities, response rates, and survival of HCL patients followed at our institution. Methods: We retrospectively reviewed data from the medical records of 56 consecutive HCL patients evaluated in our Hematology/Oncology clinic between 1998 and 2023. Results: The median age at diagnosis was 59 years (range, 37-94). Forty-nine patients (87%) were male. First-line therapy was cladribine in 30 patients (54%), cladribine + rituximab in 6 patients (11%), observation in 5 patients (9%), and another modality (fludarabine, pentostatin, single agent-rituximab, and other) in the rest of patients. The median follow-up was 122 months (1-291). The overall response rate was 96%. CR and PR rates were 68% and 28%, respectively. Relapses were observed in 44% of patients. The median OS was not reached, and the median PFS was 181 months (95% CI, 128-252). The 5-year and 10-year PFS were 78% and 29%, respectively. Only 3 patients (5%) died as a result of HCL, either indirectly from immune suppression (pneumonia, 2 patients) or directly (cachexia in 1 patient, untreated because of advanced age and comorbidities). Conclusions: Treatment with purine analogues such as cladribine, plus or minus rituximab, achieves deep and durable responses in most HCL patients. Although relapses were commonly observed, the vast majority of HCL patients did not die as a result of HLC.

Longer-term follow-up of patients (pts) receiving prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) in the phase 1/2 MajesTEC-1 study of teclistamab in relapsed/refractory multiple myeloma (RRMM).

7517 Background: Emerging data suggest that administering toci prior to bispecific antibodies reduces the incidence of CRS, which may support outpatient therapy initiation. We previously showed that the incidence of CRS with teclistamab, the first approved BCMA×CD3 bispecific antibody with weight-based dosing for the treatment of pts with triple-class exposed RRMM, was reduced from 72% in the overall MajesTEC-1 study population to 26% in a cohort receiving a single dose of toci before the first teclistamab step-up dose. Here, we present an updated analysis with longer-term follow-up. Methods: Pts with triple-class exposed RRMM received subcutaneous teclistamab 1.5 mg/kg weekly in a prospective exploratory cohort or at a comparable fixed dose, following 2 step-up doses. Toci 8 mg/kg was given intravenously ≤4 hours before the first teclistamab step-up dose. CRS was graded per Lee et al ( Blood 2014;124:188-95) and managed per the study protocol. Results: This analysis included 24 pts with median follow-up 8.1 months (range, 0.9–13.2). Median age was 72 years (range, 50–82); 100% had ECOG PS score ≤1; 96% had International Staging System stage I/II; 74% had standard-risk cytogenetics; 21% had extramedullary plasmacytomas; 33% had ≥30% bone marrow plasma cells (biopsy or aspirate). Pts had a median of 4 prior lines of therapy (range, 2–9); 58% were triple-class refractory. CRS occurred in 6 pts (25%; 2 grade 1, 4 grade 2, no grade ≥3); 3 pts each had 1 recurrent CRS event. Median time to CRS onset was 2 days (range, 1–3); median duration was 2 days (range, 2–4). CRS was managed with additional toci in 5/6 pts and steroids in 1/6; all CRS events resolved and none led to teclistamab discontinuation. Most common adverse events (AEs; any grade/grade 3/4) were infections (79%/25%), neutropenia (63%/63%), and anemia (58%/25%); 5 pts had a neurotoxicity AE (grade 1 dizziness; grade 1 headache; grade 1 insomnia; grade 2 headache; grade 2 immune effector cell-associated neurotoxicity syndrome). Overall response rate (n=22) was 73% (59% very good partial response or better). Timing of interleukin (IL)-6 induction in the prophylactic toci cohort was consistent with the phase 1 MajesTEC-1 population, with higher IL-6 levels as observed in other studies of IL-6 receptor-blocking antibodies. Conclusions: Prophylactic toci reduced the incidence of CRS with teclistamab, with a 65% relative reduction vs the overall MajesTEC-1 population (grade 1, 8% vs 50%; grade 2, 17% vs 21%). No new safety signals or impact on response to teclistamab was observed with longer follow-up. Prophylactic toci may be a useful measure to consider when selecting pts for outpatient administration of teclistamab in the future. This approach is being evaluated in the phase 2, multicenter, prospective OPTec study (NCT05972135). Clinical trial information: NCT03145181 / NCT04557098 .

Prevalence of Gastroesophageal Reflux Disease in Congenital Diaphragmatic Hernia Survivors From Infancy to Adulthood

BackgroundGastroesophageal reflux disease (GERD) is a common comorbidity associated with congenital diaphragmatic hernia (CDH), with reported cases of Barrett's esophagus (BE) and esophageal adenocarcinoma before the age of 25. The prevalence and natural course of GERD in CDH survivors remain uncertain due to variations in diagnostic methods. We aimed to analyse the GERD prevalence from infancy through young adulthood. MethodsWe retrospectively analyzed pH-impedance measurements and endoscopic findings in 96 CDH survivors evaluated as routine care using well established clinical protocols.GERD was defined as an abnormal acid exposure time for pH-MII measurements and as presence of reflux esophagitis or BE at upper endoscopy. Clinical data including symptoms at time of follow-up and use of antireflux medication were collected. ResultsGERD prevalence remained consistently low (≤10%) across all age groups, yet many patients experienced GER symptoms. Histological abnormalities were observed in 80% of adolescents and young adults, including microscopic esophagitis in 50%. BE was diagnosed in 7% before the age of 18, all had GER symptoms. CDH severity, anatomy at the time of CDH correction, alcohol usage, and smoking did not emerge as significant risk factors for GERD. ConclusionsGiven the low GERD prevalence in CDH survivors, a symptom-driven approach to diagnosis and follow-up is warranted. We advise long-term follow-up for all adult patients due to the early onset of BE and the limited evidence available. The longitudinal course and impact of GERD on other long-term CDH-related comorbidities should be explored in larger cohorts. Level of EvidenceNot applicable

Long-term Outcome of Coronavirus Disease-associated Mucormycosis: 1-year Follow-up Study from India.

Invasive fungal infections have recently become a public health problem, particularly in India following the second wave of coronavirus disease 2019 (COVID-19). India harbors the world's largest population of patients suffering from diabetes. What prompted the sudden spike of mucormycosis infections in the COVID pandemic needs investigation. To determine if COVID-19 infection prompted the spike in invasive fungal infections in diabetic population. To determine the long-term outcome of COVID-associated mucormycosis. To determine if COVID-19 infection causes diabetes mellitus transiently. The study was a prospective cohort study comprising patients suffering from mucormycosis. The study was planned from 20 May 2021, until 30 November 2022, to investigate the long-term follow-up (1 year) of mucormycosis patients. The study setting was a referral hospital. All the consecutive patients admitted to this hospital for treatment of mucormycosis were included in the study who consented to it. Intervention(s) (for clinical trials) or exposure(s) (for observational studies): All patients suffering with mucormycosis underwent treatment at this hospital with surgery and injectable systemic antifungal drugs alongside diabetes management. Primary outcome measurement was in the form of survival with cure of mucormycosis. Hypothesis being tested was formulated during data collection. The data of 98 participants was collected, but analysis was done after excluding the case of cutaneous mucormycosis (infant patient). Mean age for patients was 55.5 years, varying from 28 to 88 years. In our study, 63.3% of patients with mucormycosis were males and 37.8% were females, of which 55.7% (34) and 58.3% (21) were known diabetics, respectively. Previous history of diabetes mellitus was identified as an underlying comorbid condition in 56.7% of patients, while the rest were diagnosed with new-onset diabetes mellitus. Sugar levels ranged (on admission) from 112 to 494 mg/dL (median 212 mg/dL) for known diabetics and from 132 to 356 mg/dL (median 204 mg/dL) for newly diagnosed diabetics. Other comorbidities included hypertension (19.5%), ischemic heart disease (8.2%), chronic renal illness (3.09%), and one case (1.03%) of postoperative renal cell carcinoma (disease-free). The majority of cases (91.8%) were not vaccinated for COVID-19, while only two patients reported a history of vaccination with two doses, and six others had received only a single dose. At the 1-year follow-up, 57.7% of cases were disease-free, 30.9% had expired, and 11.3% were lost to follow-up. The mean glycated hemoglobin (HbA1c) at the time of admission was found to be statistically significant when compared between known diabetics and newly diagnosed ones [confidence interval (CI)-95%, p ≤ 0.01]. A total of seven patients from the newly diagnosed diabetic group no longer required medicines for diabetes at the end of 1 year (CI-95%, p ≤ 0.01). Diabetes mellitus, particularly with poor glycemic control, was the single most important factor associated with and predictor of outcome. Contrary to the popular hypothesis, industrial oxygen and oxygen masks were not the reasons for the mucormycosis pandemic. Additionally, immunization against COVID provided protection not only from severe COVID but also from COVID-associated mucormycosis. It is recommended that patients with mucormycosis be followed for longer periods as a few patients could be suffering from transient diabetes, particularly against the backdrop of a pandemic.