Follow-up Time Research Articles

Short-term Outcome of RPVBT Combined with Chemotherapy for Patients with Single, < 3 cm, T2 Stage Bladder cancer

BackgroundTo investigate the survival outcome of “radical” GreenLight photoselective vaporization of bladder tumor (RPVBT) in conjunction with postoperative chemotherapy for patients with single, < 3 cm in diameter, T2 stage muscle invasive bladder cancer (MIBC).MethodsThirty-eight patients with single, < 3 cm, T2 stage bladder cancer were treated with RPVBT combined with chemotherapy and were included in the RPVBT group. To compare the differences in survival outcome, 80 patients with Ta/T1 bladder cancer and 30 patients with T2 bladder cancer were included as controls. The 80 patients with Ta/T1 bladder cancer underwent GreenLight photoselective vaporization of bladder tumors(PVBT), while 30 patients with T2 bladder cancer underwent radical cystectomy (RC) combined with pelvic lymph node dissection (PLND). Tumor recurrence and death were recorded, and recurrence-free survival (RFS) and overall survival (OS) curves were plotted to compare the survival difference between the RPVBT and control groups.ResultsNo significant differences were observed in comorbidities or living habits between the RPVBT and control groups. Blood loss [RPVBT: 20 (IQR10, 20) vs. RC: 100 (IQR90, 150) mL] and postoperative hospital stay [RPVBT: 5.5 (IQR5, 6), vs. RC: 10 (IQR8, 12) days] in the RPVBT group were significantly lower than that in the RC group. Urinary tract infection [RPVBT: 6 (15.8%) vs. PVBT: 14 (17.5%)] and bladder irritation sign [RPVBT: 11 (28.9%) vs. PVBT: 23 (28.8%) ] were the most common short-term complications in the RPVBT group, with no statistical difference between the RPVBT and PVBT group. The median follow-up time for survival endpoints was 22 (16, 27) months for the included patients after surgery. The outcomes of tumor recurrence at 12, 24, and 36 months were 2 (5.3%), 3 (7.9%), and 5 (13.2%) patients in the RPVBT groups, 13 (16.3%) and 3 (10%) patients experienced recurrence in the PVBT and RC groups at 36 months. No significant differences were noted among the three groups (P = 0.778). Additionally, Kaplan–Meier survival analysis revealed no statistically significant differences in RFS (P = 0.791) and OS (P = 0.689) among the three groups.ConclusionsOur findings indicate that RPVBT combined with chemotherapy is a simple and feasible treatment option with fewer complications and satisfactory survival outcomes in patients with single, < 3 cm, T2 stage bladder cancer.

Endovascular treatment of ruptured basilar artery trunk aneurysms: complications and long-term outcomes

ObjectTreatment of ruptured basilar artery trunk (BAT) aneurysms is challenging, and is associated with high complication and mortality rates. Herein, we analyzed the complications, long-term outcomes, and outcome predictors of endovascular treatment for ruptured BAT aneurysms. MethodsBetween January 2011 and July 2023, 36 patients with 36 ruptured BAT aneurysms underwent endovascular treatment at our institution. The postprocedural complications and clinical and angiographic outcomes were subsequently reviewed, and the risk factors for postprocedural complications were evaluated. ResultsAll 36 aneurysms in 36 patients were treated successfully. The median clinical follow-up time was 47.0 (IQR: 10.5, 84.5) months. Overall, complications occurred in 10 (27.8%) patients, including 3 (8.3%) deaths. Ischemic events occurred in seven (19.4%) patients, while three (8.3%) patients had shunt-dependent hydrocephalus, of whom one (2.8%) patient had both shunt-dependent hydrocephalus and ischemic events. The cumulative survival rates at 3 and 5 years were 94.1% and 87.8%, respectively. The cumulative 3- and 5-year complication-free survival rates were 75.0% and 70.0%, respectively. Multivariate Cox regression analysis revealed that diabetes mellitus (HR:8.76, 95%CI:2.35-32.69, p=0.001), and Glasgow coma scale score ≤ 12 before the procedure (HR:5.04, 95%CI:1.40-18.12, p=0.013) were associated with overall postprocedural complications. The complete aneurysm occlusion rate was 61.5% at a median angiography follow-up time of 6.0 (IQR: 5.0, 6.0) months. ConclusionsEndovascular treatment is a safe and feasible option for treating ruptured BAT aneurysms. The rate of favorable outcomes at the final follow-up was satisfactory. However, postprocedural complications, particularly ischemic events, should be carefully considered.

Change in physical activity and its association with decline in kidney function: A UK Biobank-based cohort study.

Previous research on the association between physical activity (PA) and kidney function is inconsistent. The association between muscle mass and serum creatinine (SCr) may have implications for interpreting the effect of PA on estimated glomerular filtration rate (eGFR). Few studies have reported changes in physical activity and changes in kidney function. A cohort study was constructed using the UK Biobank. Changes in physical activity were self-reported as metabolic equivalent task (MET) minutes/week. eGFR was calculated using SCr and cystatin C (CysC). Cox and nonlinear regressions with restricted cubic splines were applied to explore the association between changes in physical activity and rapid decline of kidney function (RDKF, eGFR annual decrease ≥3mL/min/1.73m2), and the annual change of eGFR. An exploratory analysis of cardiorespiratory fitness as the exposure was conducted. Among 11757 participants, the median follow-up time was 4.4years. Participants whose PA decreased by 1000 MET minutes/week at the follow-up assessment had a 2% reduction in risk of developing RDKFSCr (HR=0.98, 95% CI: 0.96, 1.00). In contrast, a 1000 MET minutes/week increase in PA was associated with a 4% reduction in risk of developing RDKFCysC (HR=0.96, 95% CI: 0.93, 0.99). A PA increase of 1000 MET minutes/week was associated with eGFRCysC annual increase of 0.04mL/min/1.73m2 (95% CI: 0.03, 0.06) but no significant changes in eGFRSCr. In this general population study, there are differing associations between changes in PA and changes in kidney function depending on the kidney biomarker used. Increasing PA is modestly associated with improving annual eGFRCysC and reduced risk of RDKF.

Prognostic factors in patients with intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan–Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 ± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25–201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (≤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I–III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (≤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.

Longitudinal outcomes of ischemic versus hemorrhagic stroke: Differences may impact future trial design

ObjectivesPatients with intracerebral hemorrhage (ICH) are more likely to present with severe symptoms than those with ischemic stroke (IS); however, the way in which long-term outcomes differ between groups is less clear. Given that the tissue surrounding ICH is not always irreversibly infarcted, it may have the potential to recover more fully over time. Understanding the differences in expected outcome severity is critical in order to prognosticate and to determine appropriate outcome measures when designing clinical trials. Materials and MethodsWe used our prospectively collected stroke registry to identify and follow a cohort of 300 patients with ICH and 300 patients with IS, matched by age, sex, lesion size, location, and admission date. Paired t-tests were used to compare modified Rankin Scores (mRS) between groups at hospital discharge, 90-day, and >12-month follow-up time points. ResultsNot surprisingly, patients with ICH had worse discharge mRS scores compared to individuals with IS (4.20 (SD 0.09) versus 3.42 (SD 0.08)). However, rather than improving, the long-term outcomes remained significantly worse for ICH patients compared to their IS matches (4.02 (SD 0.15) versus 2.89 (SD 0.14) at 90 days, and 4.32 (SD 0.20) versus 3.16 (SD 0.22) at >12 months (p < 0.001 for all analyses)). ConclusionsThis study longitudinally followed matched cohorts of patients with ICH and IS, confirming that outcomes for those with ICH remain significantly worse over time. Results allow for better long-term prognostication, illustrate the need for further intervention trials to improve outcomes, and inform the development of evidence-based endpoints.

Management of Patellar and Trochlear Cartilage Lesions with Matrix-Induced Autologous Chondrocyte Implantation in Conjunction with Patellofemoral Realignment Procedures Improves Patient Reported Outcomes and Magnetic Resonance Image Appearance

ObjectivesThe aim of this study is to evaluate the relationship between the achievement of clinically significant improvement in patient-reported outcome measures (PROMs) and the postoperative magnetic resonance image (MRI) appearance of matrix-associated chondrocyte implantation (MACI), in conjunction with patellofemoral realignment procedures, for the treatment of grade IV chondral defects about the patellofemoral joint. MethodsA retrospective review of patients undergoing MACI for grade IV chondral defects of the patella or trochlea by a single sports medicine fellowship-trained surgeon from 2017-2020 was performed. Concomitant realignment procedures, including tibial tubercle osteotomy and medial patellofemoral ligament reconstruction, were also performed as needed. Patients with preoperative and minimum 1-year postoperative PROMs and postoperative knee MRI were included. MRI were obtained at 6.3 [Interquartile range (IQR): 5.8, 7.5] months postoperatively. A fellowship-trained musculoskeletal radiologist assigned a Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score (range: 0-100, with 100 equating to complete graft healing) to each MRI. Achievement of the minimal clinically important difference (MCID) for International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Score–Quality of Life (KOOS-QoL), and Kujala scores were determined for each patient. Paired t-tests or Wilcoxon Rank-Sum tests were used to evaluate for an association between achievement of the MCID for each PROM and MOCART scores. The average follow-up time and time from surgery to PROMs were 2.7±1.5 years and 1.7±0.66 years, respectively. ResultsThirty patients were included. There was a significant improvement in all PROMs from pre- to postoperative (p<0.001). More than two thirds of patients achieved the MCID for each PROM. Patients who achieved the MCID for IKDC had significantly higher MOCART scores (66.5±16.2) compared to those who did not meet the MCID for IKDC (50.6±23.6, p=0.043). ConclusionMACI for the treatment of patellofemoral chondral injuries is associated with clinically significant improvement in PROMs at short-term follow up. Clinically significant improvements in IKDC scores are associated with a more mature MRI appearance of the ACI graft on postoperative MRI, as indicated by higher MOCART scores. Level of EvidenceIV – Case Series

Treatment of Persistent Soiling in Hirschsprung Disease With Antegrade Continence Enemas

IntroductionPatients with Hirschsprung disease (HD) can experience soiling after their pull-through. We evaluated the use of antegrade continence enema (ACE) for this patient population and investigated the timing and factors associated with getting the patient clean. MethodsWe performed a single-institution retrospective review (from January 2020 to January 2023) of patients with HD and prior pull-through who had persistent soiling, failed laxative treatment or rectal enemas, and were treated with antegrade enemas. The primary outcome was time to become “clean of stool” which was defined as at least one bowel movement per day, no more than one stool accident per week, and no significant stool burden radiographically. Kaplan–Meier survival analysis was performed, and univariate cox proportional hazard regression was used to assess factors associated with time to continence. ResultsThirty patients who met the criteria underwent ACE creation at a median age of 6.5 y (interquartile range 5.3-9.8) with a median follow-up time of 11.5 mo (interquartile range 5.6-16.5). Most patients became clean by 4 mo (13 of 20, 65%) with similar results at 1-y follow-up (16 of 21, 76%). The median time to becoming clean was 4.3 mo (95% confidence interval: 1.7-15.0. Patients with hypermotility were more likely to continue to soil at 1 y (80% versus 13%, P = 0.01). There were no additional factors significantly associated with time to cleanliness. ConclusionsACE is a useful modality for HD patients with soiling. Most became clean of stool in 4 mo. The presence of hypermotility was associated with a higher incidence of persistent soiling at 1 y.

The current role of adjuvant radiotherapy in management of medullary thyroid carcinoma: A single institute analysis.

Medullary thyroid carcinoma (MTC) accounts for only about 5% of total thyroid cancers. It usually presents as an advanced disease carrying a poor prognosis than well-differentiated thyroid cancers. While the treatment of choice is surgery, the role of adjuvant radiotherapy is still unclear. This retrospective study aims to understand the role of adjuvant radiotherapy in MTC and its effect on survival. We did a retrospective two study to estimate the effect of adjuvant external beam radiotherapy (EBRT) on survival outcomes in MTC. A total of 30 patients who were diagnosed with nonmetastatic MTC during the period 2015 to 2020 were included in the study. Fifteen patients underwent only total thyroidectomy with cervical lymph node dissection. Rest 15 patients received adjuvant EBRT following surgery. A median dose of 60 Gy in 30 fractions, 2 Gy per fraction, 5 days per week, was given by conventional radiotherapy technique. Survival outcomes were estimated using Kaplan-Meier method. A univariate analysis using log rank test was performed to estimate the association of various prognostic factors including age, sex, tumor size, nodal involvement, and surgical resection status on survival outcomes. Median age of presentation in our study is 47 years (inter quartile range: 36-55 years). Median follow-up time is 4 years. Male to female ratio is 2:3-70% of patients presented with T3 lesions and 77% with N1b disease. There was no significant difference in overall survival (OS) in patients who received adjuvant RT following surgery in comparison to patients who underwent only surgery (92.9% vs. 71.4% P value = 0.202). Similarly, there was no improvement in locoregional recurrence-free survival (LRFS) (100% vs. 85.7%, P value-0.157), Distant metastasis-free survival (DMFS) (64.3% vs. 71.4%, P value = 0.725), and Disease-free survival (DFS) (64.3% vs. 64.3%, P value = 0.91). Age, gender, nodal involvement, and surgical resection status (R0, R1, R2) did not have any effect on survival outcomes. DFS (100% vs. 63.6% P value = 0.008), LRFS (100% vs. 94.7% P value = 0.002), and DMFS (100% vs. 63.2% P value = 0.006) were significantly better in T2 lesions compared to advanced lesions. Adjuvant EBRT failed to show any significant improvement in survival outcomes and locoregional control in MTC. Further prospective randomized clinical trials are needed to validate the role of EBRT in MTC. Clinicians should proceed with caution before advising adjuvant radiotherapy in MTC and make an informed decision after weighing the pros and cons of giving adjuvant EBRT.

Incidence of de novo malignancy and all-cause mortality among heart transplant recipients

BackgroundHeart transplant recipients develop cancer at two-times the rate compared to the general population. However, the incidence and mortality rates and the adjusted association between cancer and mortality remains unclear. MethodsWe estimated the incidence and mortality rates and the adjusted association between developing cancer (any, skin, hematologic, and solid tumor subtypes) and the all-cause mortality rates among adult heart transplant recipients from the Scientific Registry of Transplant Recipients from October 1, 1987, until June 28, 2020. ResultsAmong 51,597 adult heart transplant recipients, 13,191 (25.6%) were diagnosed with de novo malignancy throughout the follow-up period. The cumulative incidence cancer at years 1, 5, 10, and 20 was 3%, 16.4%, 32.8%, and 56.6%, respectively. Among those with cancer, the cumulative mortality was 17.5%, 42.3%, 65%, and 91% at years 1, 5, 10, and 20, respectively. The incidence rate of any de novo malignancy was 38.7 cases per 1000 person-years and the mortality rate (for those with cancer) was 115.2 cases per 1000 person-years. Compared to those without cancer, those with cancer had a higher adjusted mortality association [HR: 2.14 (2.07, 2.21)]. The strongest associations were estimated for pancreatic [10.63 (8.34, 13.54)], leukemia [8.06 (4.33, 15.00)], and esophagus [6.94 (5.43, 8.87)] malignancies. The association between de novo malignancies and mortality was higher in the earlier years of follow-up. ConclusionCompared to not developing cancer, those with de novo malignancy have a 2-fold higher mortality rate, on average. The strength of the association varies by cancer subtype and by follow-up time.

Clinical Characteristics and Outcomes of Dilated Cardiomyopathy in Chinese Children: A Single-Center Retrospective Study.

The reported outcomes of pediatric dilated cardiomyopathy (DCM) have varied across studies. There are few outcome data concerning DCM in Chinese children. Therefore, we conducted a retrospective study to describe clinical features and determine risk factors for poor outcomes in children with DCM. We enrolled 121 children with DCM in our hospital from 2003 to 2021. General information and laboratory and echocardiographic data were collected and analyzed. Cox regression analysis was performed to determine risk factors for poor outcomes. This study included 121 patients (69 males and 52 females). The median age at diagnosis was 10.8 years, and the follow-up time was 10.0 months. Eighty-two patients (67.8%) exhibited cardiac function classes III-IV at the time of diagnosis. Tachypnea was the most common symptom (78.5%). In echocardiography, the mean left ventricular end-diastolic dimension z score was 7.36 ± 2.73, and the left ventricular ejection fraction z score was -6.58 ± 2.17. The 1-, 2-, and 5-year survival rates were 51.2%, 43.8%, and 32.2%, respectively. Cox analysis revealed that cardiac function classes III-IV (hazard ratio [HR] = 1.801, 95% confidence interval [95% CI] = 1.030-3.149, p = 0.039) and calcium levels (HR = 0.219, 95% CI = 0.084-0.576, p = 0.002) were predictors of poor outcomes in children with DCM. Children with DCM are at high risk of death. Cardiac function class III-IV and calcium levels were related to the prognosis of pediatric DCM patients.

Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor–Positive Breast Cancer

Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking. To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer. This prospective-retrospective translational study used all available tumor tissue samples from female patients from the Suppression of Ovarian Function Trial (SOFT). These individuals were randomized to receive 5 years of adjuvant tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS. BCI testing was performed blinded to clinical data and outcome. The a priori hypothesis was that BCI HOXB13/IL17BR ratio (BCI[H/I])-high tumors would benefit more from OFS and high BCI portended poorer prognosis in this population. Settings spanned multiple centers internationally. Participants included premenopausal female patients with HR+ early breast cancer with specimens in the International Breast Cancer Study Group tumor repository available for RNA extraction. Data were collected from December 2003 to April 2021 and were analyzed from May 2022 to October 2022. Primary end points were breast cancer-free interval (BCFI) for the predictive analysis and distant recurrence-free interval (DRFI) for the prognostic analyses. Tumor specimens were available for 1718 of the 3047 female patients in the SOFT intention-to-treat population. The 1687 patients (98.2%) who had specimens that yielded sufficient RNA for BCI testing represented the parent trial population. The median (IQR) follow-up time was 12 (10.5-13.4) years, and 512 patients (30.3%) were younger than 40 years. Tumors were BCI(H/I)-low for 972 patients (57.6%) and BCI(H/I)-high for 715 patients (42.4%). Patients with tumors classified as BCI(H/I)-low exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48 [95% CI, 0.33-0.71]) and an absolute benefit of 7.3% from tamoxifen plus OFS (HR, 0.69 [95% CI, 0.48-0.97]) relative to tamoxifen alone. In contrast, patients with BCI(H/I)-high tumors did not benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03 [95% CI, 0.70-1.53]; P for interaction = .006) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05 [95% CI, 0.72-1.54]; P for interaction = .11) compared with tamoxifen alone. BCI continuous index was significantly prognostic in the N0 subgroup for DRFI (n = 1110; P = .004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk N0 cancers, respectively. In this prospective-retrospective translational study of patients enrolled in SOFT, BCI was confirmed as prognostic in premenopausal women with HR+ breast cancer. The benefit from OFS-containing adjuvant endocrine therapy was greater for patients with BCI(H/I)-low tumors than BCI(H/I)-high tumors. BCI(H/I)-low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.

Comparison of immunochemotherapy followed by surgery or chemoradiotherapy in locally advanced esophageal squamous cell cancer

BackgroundSeveral studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. MethodsPooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. ResultsThe median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). ConclusionThe differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.

Transanal circumferential pouch advancement for treatment of pouch vaginal fistulae

BackgroundIleal pouch anal anastomosis (IPAA) circumferential pouch advancement (CPA) involves full-thickness transanal 180–360° dissection of the distal pouch, allowing the advancement of healthy bowel to cover the internal opening of a vaginal fistula. We aimed to describe the long-term outcomes of this rare procedure.MethodsPatients with IPAA who underwent transanal pouch advancement for any indication between 2009 and 2021 were included. Demographics, operative details, and outcomes were reviewed. An early fistula was defined as occurring within 1 year of IPAA construction. Clinical success was defined as resolution of symptoms necessitating CPA, pouch retention, and no stoma at the time of follow-up. Figures represent the median (interquartile range) or frequency (%).ResultsOver a 12-year period, nine patients were identified; the median age at CPA was 41 (36–44) years. Four patients developed early fistula after index IPAA, and five developed late fistulae. The median number of fistula repair procedures prior to CPA was 2 (1–2). All patients were diagnosed with ulcerative colitis at the time of IPAA and all late patients were re-diagnosed with Crohn’s disease. Four (44.4%) patients had ileostomies present at the time of surgery, three (33.3%) had one constructed during surgery, and two (22.2%) never had a stoma. The median follow-up time was 11 (6–24) months. Clinical success was achieved in four of the nine (44.4%) patients at the time of the last follow-up.ConclusionsTransanal circumferential pouch advancement was an effective treatment for refractory pouch vaginal fistulas and may be offered to patients who have had previous attempts at repair.

Associations between gut microbiota and incident fractures in the FINRISK cohort

The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.92 per standard deviation increase in Shannon index, 95% confidence interval 0.87–0.96). For beta diversity, the first principal component was associated with fracture risk (Aitchison distance, HR 0.90, 0.85–0.96). In predefined phyla analyses, we observed that the relative abundance of Proteobacteria was associated with increased fracture risk (HR 1.14, 1.07–1.20), while the relative abundance of Tenericutes was associated with decreased fracture risk (HR 0.90, 0.85–0.96). Explorative sub-analyses within the Proteobacteria phylum showed that higher relative abundance of Gammaproteobacteria was associated with increased fracture risk. Functionality analyses showed that pathways related to amino acid metabolism and lipopolysaccharide biosynthesis associated with fracture risk. The relative abundance of Proteobacteria correlated with pathways for amino acid metabolism, while the relative abundance of Tenericutes correlated with pathways for butyrate synthesis. In conclusion, the overall GM composition was associated with incident fractures. The relative abundance of Proteobacteria, especially Gammaproteobacteria, was associated with increased fracture risk, while the relative abundance of Tenericutes was associated with decreased fracture risk. Functionality analyses demonstrated that pathways known to regulate bone health may underlie these associations.

Results of medial patellofemoral ligament reconstruction with and without tibial tubercle osteotomy in patellar instability: a systematic review and single-arm meta-analysis

PurposeTo confirm which method provides lower rate of recurrent instability and superior clinical outcomes.MethodWe searched PubMed, Embase and Web of Science for the trials involving one intervention or both for patellar instability: medial patellofemoral ligament reconstruction (MPFLR) with and without tibial tubercle osteotomy (TTO). The postoperative Kujala score, Lysholm score, Tegner scores and the rate of recurrent instability (dislocation or subluxation) were analyzed as the primary clinical outcome parameters in a random or fixed effects meta-analysis.ResultsIn total, 43 articles met inclusion criteria after full-text review. A total of 2046 patients were analyzed. The overall mean age was 20.3 years (range, 9.5–60.0 years), with a mean follow-up time of 3.2 years (range, 1–8 years). The mean Kujala scores in MPFLR and MPFLR + TTO were 89.04 and 84.44, respectively. There was significant difference in Kujala scores between MPFLR and MPFLR + TTO (MD = 4.60, 95%CI: 1.07–8.13; P = 0.01). The mean Lysholm scores in MPFLR and MPFLR + TTO were 90.59 and 88.14, respectively. There was no significant difference in Lysholm scores between MPFLR and MPFLR + TTO (MD = 2.45, 95%CI: -3.20-8.10; P = 0.40). The mean Tegner scores in MPFLR and MPFLR + TTO were 5.30 and 4.88, respectively. There was no significant difference in Tegner scores between MPFLR and MPFLR + TTO (MD = 0.42, 95%CI: -0.39-1.23; P = 0.31). At final follow-up, the rates of recurrent instability in MPFLR and MPFLR + TTO were 3% and 4%, respectively. There was no significant difference in the rates between MPFLR and MPFLR + TTO (OR = 0.99, 95%CI: 0.96–1.02; P = 0.4848).ConclusionMPFLR and MPFLR + TTO are effective and reliable treatments in the setting of patellofemoral instability. MPFLR seems to show a better performance in functional outcomes than MPFLR + TTO. Moreover, their rates of recurrent instability are very low, and no significant difference exists.

Geriatric femur fractures: Index fracture pattern is associated with the risk of subsequent peri-implant fracture

IntroductionFollowing an index femoral fragility fracture, patients are at risk of a subsequent peri-implant fracture. Management of these injuries are further complicated by patient factors and multi-institutional care. This study quantifies such events and compare rate of identification between in-system and out-of-system patients. MethodsA retrospective chart review of index operative femoral fragility fractures at a level I trauma center from January 1, 2005 to January 1, 2018 identified 840 patients with twenty-two subsequent peri-implant fractures. Kaplan Meier survival analyses assessed associations between patient and injury characteristics with the subsequent fracture while accounting for differential follow-up. Cumulative incidence curves were reported, and Cox regression analyses estimated hazard ratios for statistically significant associations. In-system and out-of-system patients were compared with absolute rate of identifying subsequent fracture and follow-up time. ResultsCumulative incidence of subsequent fracture was 2.1 % at 2 years, 3.4 % at 4 years, and 4.6 % at 6 years. The index fracture pattern (intertrochanteric vs other) was associated with a cumulative incidence of subsequent peri-implant fracture (0.8 % at 2 years, 1.4 % at 4 years, and 2.7 % at 6 years for intertrochanteric fractures vs 3.4 % at 2 years, 5.3 % at 4 years, and 6.4 % at 6 years for non-intertrochanteric fractures), p = 0.029. Follow-up was shorter for out-of-system patients (median 6 versus 28 months, p < 0.001), and only 1 of 348 out-of-system patients (0.3 %) vs. 21 of 492 in-system patients (4.3 %) were diagnosed with a subsequent peri-implant fracture (p < 0.001). There was no association of subsequent peri-implant fracture with patient demographics or comorbidity burden. ConclusionCumulative incidence of subsequent peri-implant fracture was higher for non-intertrochanteric (femoral neck, shaft and distal femur) fractures than intertrochanteric fractures. Out-of-system patients had shorter follow-up and were less likely to be diagnosed with a subsequent peri-implant fracture, indicating ascertainment bias and underscoring the importance of accounting for loss to follow-up. Level of evidenceTherapeutic Level III.

Efficacy and safety of bintrafusp alfa in 2 phase I expansion cohorts with advanced HCC.

Simultaneous inhibition of the TGF-β and programmed cell death 1 ligand 1 pathways provides a potential novel treatment approach. Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death 1 ligand 1, was evaluated in patients with advanced HCC. In this global, open-label, phase I study (NCT02517398), patients with programmed cell death 1 ligand 1-unselected HCC who failed or were intolerant to ≥1 line of sorafenib received bintrafusp alfa 1200mg every 2 weeks in a dose-escalation (n = 38) or dose-expansion (n = 68) cohort until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was the best overall response per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee. Secondary endpoints included investigator-assessed best overall response, safety, and pharmacokinetics. Median follow-up times (range) were 41.4 (39.8-44.2) and 38.6 (33.5-39.7) months in the dose-escalation and dose-expansion cohorts, respectively. The objective response rate was below the prespecified 20% objective response rate threshold set to evaluate the efficacy of bintrafusp alfa in both cohorts (10.5% and 8.8%, respectively). Median overall survival and progression-free survival, respectively, were 13.8 and 1.5 months in the dose-escalation cohort and 13.5 and 1.4 months in the dose-expansion cohort. Treatment-related adverse events occurred in 78.9% and 64.7% of patients in the respective cohorts (grade ≥3 in 18.4% and 25.0% of patients). Bintrafusp alfa showed moderate clinical activity and a safety profile consistent with previous studies of bintrafusp alfa in patients with advanced HCC.

Associations of Amyloid Burden, White Matter Hyperintensities, and Hippocampal Volume With Cognitive Trajectories in the 90+ Study.

Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old. This was a longitudinal, observational community-based cohort study. We included participants with 18F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors. The sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (βMMSE = -0.82, 95% CI -1.17 to -0.46; β3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline. Amyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.

Prognostic Impacts of Age, Diagnosis Time, and Relapses in Primary CNS Lymphoma.

Background: The incidence of lymphomatous involvement of the central nervous system (CNS) has been increasing in recent years. However, the rarity of the disease has resulted in a scarcity of available data regarding its clinical presentation, natural history, and prognosis. We aimed to investigate the neurological characteristics of uncommon lymphomatous involvements confined to the CNS and to identify key variables that could serve as predictive biomarkers for treatment outcomes. Methods: We identified patients presenting with neurological symptoms and diagnosed with CNS-restricted lymphomatous involvement between 2005 and 2023. Results: We identified 44 cases, 93% of which were diagnosed with primary central nervous system lymphoma (PCNSL) and 7% with intravascular lymphoma. The median time from symptom onset to diagnosis was 47 days (range: 6-573 days), with no statistically significant difference between patients older and younger than 60 years (p = 0.22). The median follow-up time was 1144 days (range: 27-3501 days). Cognitive deterioration was the most common presenting symptom, occurring in 19 out of 44 patients (43%). Brain MRI revealed that lobar lesions were the most frequent location of lesions, found in 24 out of 44 patients (55%). By the end of the study period, 30 patients (68%) had died, with a median survival of 666 days (range: 17-3291 days). Death was significantly more common in patients who experienced relapses (p = 0.04; 95% CI: 0.99-0.03), with these patients having a four times higher chance of death (HR = 4.1; 95% CI: 1.01-16.09). The time to diagnosis significantly correlated with survival (p = 0.02; 95% CI: 0.005-0.54), as did the Eastern Cooperative Oncology Group (ECOG) performance status at the last follow-up (p = 0.006; 95% CI: 0.0012-0.62). Patients aged over 60 years did not exhibit a higher likelihood of death (p = 0.19; HR = 2.3; 95% CI: 0.63-8.61); however, the threshold age at diagnosis for the maximally predicted mortality was 64 years (ROC = 0.73; p = 0.03). Conclusions: Patients had significant delays in diagnosis, affecting patient outcomes. Cognitive deterioration and lobar lesions were prominent clinical and radiological features. Mortality was notably higher in patients with relapses and those who had a longer time to diagnosis.

Exploring Radiotherapy as a Promising Alternative for Managing Advanced Upper Tract Urothelial Carcinoma: Rescuing Chemotherapy-Intolerant Patients

PurposeTo investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) patients intolerant to chemotherapy. MethodsData for 21 patients with advanced UTUC intolerant to chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-70 Gy/20-33 f) or partial-SABR boost to the lesions (50-60 Gy/20-25 f with tumor center boosted with 6-8 Gy/f, 3-5 f) for bulky tumors. ResultsThe median age was 75 years (range, 58-87 years). Primary tumor resection was performed for all patients and none underwent metastatic resection. Seventeen (81%) patients had oligometastasis (1-5 metastases) at diagnosis. Eighteen (85.7%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/21). Other lesions were distributed as local recurrence (7/21), bone metastases (2/21) and abdominal wall/muscle (2/21). The median follow-up time was 38.5 months (interquartile range, 15.2-48.7 months). Rate of local control (LC), progression-free survival (PFS) and overall survival (OS) of the whole group at 1 year were 90%, 46.6%, and 80.4%, respectively. At 3 years, LC, PFS and OS were 65.6%, 26.6%, and 40.9%, respectively. Fourteen patients developed acute mild gastrointestinal toxicity, generally of grade 1-2; 8 patients developed acute grade 1-2 hematological toxicity, consisting mainly of anemia and leukopenia. No grade 3 or higher acute or late toxicities were observed. ConclusionFor patients with advanced UTUC who are not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control.