Hematuria Cancer Risk Score with Ultrasound Informs Cystoscopy Use in Patients with Hematuria.

BACKGROUND: Hematuria is a cardinal symptom of urinary tract cancer and would require further investigations. OBJECTIVE: To determine the ability of renal bladder ultrasound (RBUS) with the Hematuria Cancer Risk Score (HCRS) to inform cystoscopy use in patients with hematuria. DESIGN, SETTING, AND PARTICIPANTS: The development cohort comprised 1984 patients with hematuria from 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) who received RBUS. An independent validation cohort comprised 500 consecutive patients referred to secondary care for a suspicion of bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity and true negative of the HCRS and RBUS were assessed. RESULTS AND LIMITATIONS: A total of 134 (7%) and 36 (8%) patients in the development and validation cohorts, respectively, had a diagnosis of urinary tract cancer. Validation of the HCRS achieves good discrimination with an area under the receiver operating characteristic curve of 0.727 (95% confidence interval 0.648-0.800) in the validation cohort with sensitivity of 95% for the identification of cancer. Utilizing the cutoff of 4.500 derived from the HCRS in combination with RBUS in the development cohort, 680 (34%) patients would have been spared cystoscopy at the cost of missing a G1 Ta bladder cancer and a urinary tract cancer patient, while 117 (25%) patients would have avoided cystoscopy at the cost of missing a single patient of G1 Ta bladder cancer with sensitivity for the identification of cancer of 97% in the validation cohort. CONCLUSIONS: The HCRS with RBUS offers good discriminatory ability in identifying patients who would benefit from cystoscopy, sparing selected patient cohorts from an invasive procedure. PATIENT SUMMARY: The hematuria cancer risk score with renal bladder ultrasound allows for the triage of patients with hematuria who would benefit from visual examination of the bladder (cystoscopy). This resulted in 25% of patients safely omitting cystoscopy, which is an invasive procedure, and would lead to health care cost savings.

Complications and survival rates of subtrochanteric fractures are similar between short and long intramedullary nail fixation and independent of weight-bearing.

PURPOSE: Intertrochanteric fractures are treated surgically, allowing rapid weight-bearing to improve ambulation and lower complications and mortality. Subtrochanteric fractures are mechanically less stable and are traditionally treated with a non-weight approach and longer intramedullary nails. This study compared immediate weight-bearing versus limited weight-bearing and different intramedullary nail lengths regarding patient outcomes. METHODS: We analyzed all consecutive cases of low-energy subtrochanteric fractures treated surgically at our institution between January 2016 and November 2020. One hundred and nine patients were found. We compared nail length and immediate versus delayed weight-bearing concerning the length of stay, time to painless ambulation, time to radiographic fracture union, and revision rates. Fracture severity was also examined using the Seinsheimer classification. RESULTS: Length of stay and time to painless ambulation were shorter in the immediate weight-bearing group. Time to radiographic union and rate of complications were lower; however, they were not statistically significant. Conversely, no significant difference in revision rates was found. Regarding nail length, the length of stay was shorter, and the time to painless ambulation was faster in the short-length group. The rate of complications and time to union were similar. No difference in revision rate was found. Seinsheimer classification of the fracture did not influence the decision to allow weight-bearing or nail selection (p = 0.65). CONCLUSIONS: This study demonstrates that immediate weight-bearing as tolerated and short intramedullary nails allow a quicker time for painless ambulation and hospitalization, with possibly fewer perioperative complications and faster radiographic union, without increasing complications.

The Cross-talk Between Intestinal Microbiota and MDSCs Fuels Colitis-associated Cancer Development.

Intestinal chronic inflammation is associated with microbial dysbiosis and accumulation of various immune cells including myeloid-derived suppressor cells (MDSC), which profoundly impact the immune microenvironment, perturb homeostasis and increase the risk to develop colitis-associated colorectal cancer (CAC). However, the specific MDSCs-dysbiotic microbiota interactions and their collective impact on CAC development remain poorly understood. In this study, using a murine model of CAC, we demonstrate that CAC-bearing mice exhibit significantly elevated levels of highly immunosuppressive MDSCs, accompanied by microbiota alterations. Both MDSCs and bacteria that infiltrate the colon tissue and developing tumors can be found in close proximity, suggesting intricate MDSC-microbiota cross-talk within the tumor microenvironment. To investigate this phenomenon, we employed antibiotic treatment to disrupt MDSC-microbiota interactions. This intervention yielded a remarkable reduction in intestinal inflammation, decreased MDSC levels, and alleviated immunosuppression, all of which were associated with a significant reduction in tumor burden. Furthermore, we underscore the causative role of dysbiotic microbiota in the predisposition toward tumor development, highlighting their potential as biomarkers for predicting tumor load. We shed light on the intimate MDSCs-microbiota cross-talk, revealing how bacteria enhance MDSC suppressive features and activities, inhibit their differentiation into mature beneficial myeloid cells, and redirect some toward M2 macrophage phenotype. Collectively, this study uncovers the role of MDSC-bacteria cross-talk in impairing immune responses and promoting tumor growth, providing new insights into potential therapeutic strategies for CAC. SIGNIFICANCE: MDSCs-dysbiotic bacteria interactions in the intestine play a crucial role in intensifying immunosuppression within the CAC microenvironment, ultimately facilitating tumor growth, highlighting potential therapeutic targets for improving the treatment outcomes of CAC.

Approach to esophageal absent contractility: can we do better?

Absent contractility (AC), a motility disorder characterized by the absence of esophageal contractions while maintaining normal lower esophageal sphincter relaxation, is recognized as a distinctive major disorder of peristalsis on esophageal high-resolution manometry that warrants comprehensive understanding. This unique motility disorder often co-occurs with connective tissue, rheumatologic or autoimmune diseases, with scleroderma being the classic example. Symptoms of gastroesophageal reflux are common. AC can profoundly impact patients' lives and result in a spectrum of complications, including erosive esophagitis, esophageal candidiasis, Barrett's esophagus, and malnutrition. To address the intricate complexities of AC and its multifaceted complications, a multidisciplinary approach is paramount. This approach considers the distinct clinical presentation and underlying rheumatologic conditions of the individual patient, recognizing the inherent diversity within this disorder. While medical management of gastroesophageal reflux remains the cornerstone of AC treatment, emerging surgical and endoscopic interventions offer additional therapeutic options for those grappling with this challenging condition. This comprehensive review provides an in-depth evaluation of recent advances in our understanding of AC and its management. It endeavors to offer valuable insights into therapeutic strategies for AC and its associated issues.

Good Short-Term Survivorship of Constrained Condylar Revision Knee Implants With Medial Pivot Kinematics: A Level IV Retrospective Study.

BACKGROUND: The need for revision total knee arthroplasty surgery is increasing worldwide, and, in many cases, a constrained implant is required to provide joint stability. The purpose of this study was to examine the early loosening and functional outcome of a novel constrained condylar (CCK) revision total knee system designed to have medial pivot (MP) kinematics. METHODS: A retrospective cohort study was performed, collecting clinical data from all patients who underwent revision total knee arthroplasty using a novel MP CCK system with a minimum four-year clinical follow-up. Patient demographics, survivorship, complications, and Forgotten Joint Score were analyzed based upon chart review. RESULTS: There were 49 patients available for follow-up, who had a 100% survivorship free of aseptic loosening. All-cause revision survivorship was 92%. There were 4 patients who subsequently underwent rerevision. The causes for rerevision included periprosthetic joint infection in 2 patients, coronal plane instability in one patient, and a traumatic knee dislocation in one patient. There were 45 patients who completed the Forgotten Joint Score, who had an average of 49.8 (± 32.8, range 6.25 to 100). CONCLUSIONS: At 4 years, mid-term follow-up, this novel CCK revision total knee system designed to have MP kinematics had good patient-reported outcomes with no revision for aseptic loosening. Future studies should evaluate the mid- and long-term survivorship of this innovative implant.

Covalent inhibition of pro-apoptotic BAX.

BCL-2-associated X protein (BAX) is a promising therapeutic target for activating or restraining apoptosis in diseases of pathologic cell survival or cell death, respectively. In response to cellular stress, BAX transforms from a quiescent cytosolic monomer into a toxic oligomer that permeabilizes the mitochondria, releasing key apoptogenic factors. The mitochondrial lipid trans-2-hexadecenal (t-2-hex) sensitizes BAX activation by covalent derivatization of cysteine 126 (C126). In this study, we performed a disulfide tethering screen to discover C126-reactive molecules that modulate BAX activity. We identified covalent BAX inhibitor 1 (CBI1) as a compound that selectively derivatizes BAX at C126 and inhibits BAX activation by triggering ligands or point mutagenesis. Biochemical and structural analyses revealed that CBI1 can inhibit BAX by a dual mechanism of action: conformational constraint and competitive blockade of lipidation. These data inform a pharmacologic strategy for suppressing apoptosis in diseases of unwanted cell death by covalent targeting of BAX C126.

Second TURB, restaging TURB or repeat TURB in primary T1 non-muscle invasive bladder cancer: impact on prognosis?

PURPOSE: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. METHODS: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. RESULTS: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). CONCLUSION: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.

The discovery and evaluation of [18F]BMS-986229, a novel macrocyclic peptide PET radioligand for the measurement of PD-L1 expression and in-vivo PD-L1 target engagement.

PURPOSE: A same-day PET imaging agent capable of measuring PD-L1 status in tumors is an important tool for optimizing PD-1 and PD-L1 treatments. Herein we describe the discovery and evaluation of a novel, fluorine-18 labeled macrocyclic peptide-based PET ligand for imaging PD-L1. METHODS: [18F]BMS-986229 was synthesized via copper mediated click-chemistry to yield a PD-L1 PET ligand with picomolar affinity and was tested as an in-vivo tool for assessing PD-L1 expression. RESULTS: Autoradiography showed an 8:1 binding ratio in L2987 (PD-L1 (+)) vs. HT-29 (PD-L1 (-)) tumor tissues, with >90% specific binding. Specific radioligand binding (>90%) was observed in human non-small-cell lung cancer (NSCLC) and cynomolgus monkey spleen tissues. Images of PD-L1 (+) tissues in primates were characterized by high signal-to-noise, with low background signal in non-expressing tissues. PET imaging enabled clear visualization of PD-L1 expression in a murine model in vivo, with 5-fold higher uptake in L2987 (PD-L1 (+)) than in control HT-29 (PD-L1 (-)) tumors. Moreover, this imaging agent was used to measure target engagement of PD-L1 inhibitors (peptide or mAb), in PD-L1 (+) tumors as high as 97%. CONCLUSION: A novel 18F-labeled macrocyclic peptide radioligand was developed for PET imaging of PD-L1 expressing tissues that demonstrated several advantages within a nonhuman primate model when compared directly to adnectin- or mAb-based ligands. Clinical studies are currently evaluating [18F]BMS-986229 to measure PD-L1 expression in tumors.

A Novel Model to Predict Inadequate Bowel Preparation Prior to Colonoscopy Incorporating Patients' Reactions to Drinking the Laxative.

BACKGROUND AND AIMS: Prior studies have identified predictors of inadequate preparation with limited success. We aimed to build a model that could predict the likelihood of inadequate preparation by also including factors related to the patient's reaction to drinking the laxative preparation. METHODS: Demographic, clinical, and preparation-related data were prospectively collected on patients undergoing colonoscopy. An inadequate preparation was defined as a Boston Bowel Preparation Scale < 6. Statistical analyses were performed to identify predictors of inadequate preparation and create a predictive model. RESULTS: 324 patients were included (age 67 +/- 14 years, 52% male). 77 (23.7%) had inadequate preparations. Diabetes (p < 0.001), cerebrovascular accident (CVA) (p < 0.001), incomplete prep consumption (p = 0.007), high school level education and above (p < 0.001), use of Bisacodyl (p = 0.005), >10 bowel movements (p = 0.02), and use of Sodium Picosulfate or low-volume polyethylene glycol (PEG) solution (2L) compared to PEG 3L (p < 0.001) were significant variables. In a multivariate analysis, prior CVA increased the risk for inadequate preparation (OR = 4.8, CI 1.6-14.5), whereas high school level education and above (OR = 0.4, CI 0.2-0.8), consumption of Bisacodyl (OR = 0.4, CI 0.2-0.8), >10 bowel movements (OR = 0.5, CI 0.3-0.9), and use of Sodium Picosulfate (OR = 0.5, CI 0.3-0.9) decreased the risk for inadequate prep. Using these, a predictive model for patients likely to have an inadequate colon preparation was created with an area under the curve of 0.74 (35% sensitivity, 90% specificity at a cutoff point of 39%). CONCLUSION: Given the low sensitivity, this predictive model does not appear ready for clinical use. However, due to its high specificity, it may be helpful in high-risk, sicker populations by preventing inadequately prepped procedures.

Prior abdominal surgery as a potential risk factor for colonic diverticulosis or diverticulitis.

BACKGROUND: Abnormal colonic pressure profiles have been associated with an increased risk of colonic diverticulosis. A surgical history is a known risk factor for abdominal adhesions and these may lead to increased intraluminal colonic pressure. AIM: To assess whether previous abdominal surgery is associated with colonic diverticulosis or diverticulitis. METHODS: We analyzed data from a study of patients undergoing colonoscopy for different indications from 2020 through 2021. Patients completed a structured questionnaire concerning previous abdominal surgeries, dietary and lifestyle exposures including smoking, alcohol use and co-morbidities. RESULTS: Three hundred and fifty-nine patients were included in the study. The mean age was 67.6 and 46% were females. Diabetes mellitus, hypertension, ischemic heart disease, chronic obstructive pulmonary disease, chronic renal failure, and body mass index were similar in the diverticulosis and control groups. The overall prevalence of colonic diverticulosis was 25% (91/359) and 48% of the patients had previous abdominal surgery. As expected, the prevalence of diverticulosis increased with age. There was no difference in the rate of previous abdominal surgery between patients with or without diverticulosis (49% vs 47%, P = 0.78). In regards to specific surgeries, inguinal hernia repair was significantly associated with diverticulosis (52% vs 20%, P = 0.001), but not diverticulitis. In contrast, appendectomy was not associated with diverticulosis (6% vs 14%, P = 0.048). CONCLUSION: These findings suggest that post-operative abdominal adhesions inducing high colonic intraluminal pressures do not appear to be the mechanism for diverticula formation. Rather, inguinal hernia and diverticulosis may share similar connective tissue pathologies with no causative relationship between them.

Successful implementation of a quality improvement bundle to reduce opioid overprescribing following total hip and knee arthroplasty.

BACKGROUND: Opioid overprescribing is commonplace after total hip (THA) and total knee arthroplasty (TKA). Preliminary data demonstrated that approximately 32% of the opioids prescribed at discharge from our hospital following THA and TKA remain unused. This is a concern given that unused prescribed opioids are available for diversion and may result in misuse and abuse. METHODS: Pre-intervention data were collected between 1 November 2018 and 10 December 2018. An intervention bundle was then introduced, including education of patients and providers, a standardised pain management algorithm and an autopopulated discharge prescription. The aim of this quality improvement initiative was to reduce the amount of opioid (average oral morphine equivalents (OME)) dispensed (based on the discharge prescription provided) following THA and TKA at our institution by 15% by 1 April 2019. DESIGN: Using an interrupted time series design, the outcome measure was the amount of opioid (OME) dispensed from the discharge prescription provided. Process measures included the percentage of autopopulated discharge prescriptions, the percentage of patients receiving education at discharge and the percentage of nurses and residents receiving standardised education. Balancing measures included patient satisfaction with postoperative pain management, and the percentage of patients filling the second half of the part-fill or requiring a subsequent opioid prescription. RESULTS: With 600 patients identified, mean OME dispensed at discharge was reduced by 26.3% (from 522.2 to 384.9 mg) after our interventions started. Utilisation of autopopulated part-fill prescriptions was 95.8%. There was no change in patient satisfaction nor in the proportion of patients requiring an additional opioid prescription post-intervention. Only 39% of patients filled the second half of the part-fill prescription post-intervention. CONCLUSIONS: Mean OME dispensed at discharge per patient was reduced with no change in patient satisfaction after introduction of the intervention bundle.

Radiographic pneumonia in young febrile infants presenting to the emergency department: secondary analysis of a prospective cohort study.

OBJECTIVE: The lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants. STUDY DESIGN: Secondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as 'no', 'possible' or 'definite' pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias. RESULTS: Of 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias. CONCLUSIONS: Radiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population.

Background: Colorectal cancer (CRC) is a feared complication of inflammatory bowel disease (IBD). We aimed to investigate the prevalence and risk factors of CRC among a large cohort of IBD patients. Methods: Data on IBD patients free of CRC at baseline was extracted using the MDClone platform of the Clalit health maintenance organization in Israel. We investigated the frequency rate of CRC among IBD patients compared to a control group without IBD. Possible risk factors, including comorbidities and IBD-related medications, were investigated in a multivariate analysis. Results: During a follow-up of 139,448 years among Crohn's disease (CD) patients and 139,533 years among ulcerative colitis (UC) patients, a frequency rate of CRC was 1.5% (191) among 12,888 CD patients and 2.1% (261) among 12,381 UC patients compared to 1.2% among 57,334 controls. In a multivariate analysis of UC patients, age at diagnosis (OR 1.030, p < 0.001), primary sclerosing cholangitis (OR 2.487, p = 0.005), diabetes mellitus (OR 2.01, p < 0.001), and glucocorticoids treatment (OR 1.465, p = 0.008) were found to be predictors of CRC. For CD patients, age at diagnosis (OR 1.035, p < 0.001), primary sclerosing cholangitis (OR 2.25, p = 0.029), and glucocorticoids treatment (OR 2.07, p < 0.001) were found to be predictors for CRC, but not diabetes mellitus. Conclusion: Despite the continuously decreasing rates of CRC among IBD patients, these are still higher in IBD patients compared to the general population. IBD patients, particularly those with risk factors, require special consideration in follow-up for CRC.

Ethnic Differences in Anorectal Manometry Findings in Patients With Fecal Incontinence: Results From a Multiethnic Cohort According to the London Classification.

Background/Aims: Clinical rates of fecal incontinence (FI) are known to vary based on race and ethnicity. It is unclear if anorectal manometry (ARM) findings in patients with FI differ based on ethnicity. Methods: High-resolution ARM studies performed between 2014-2021 due to FI at 2 hospitals with multiethnic populations were retrospectively reviewed. Results: Four hundred and seventy-nine subjects were included--87 (18.2%) Arab Israelis, 76 (15.9%) immigrants from the former Soviet Union, and 316 (66.0%) Jewish Israelis. Median age was 67 years old (76.0% women: 90.4% were parous). The Arab Israeli group had higher rates of smoking, diabetes, and obesity. Over 95% of ARM's were abnormal per the London classification including 23% with "combined anal hypotension and hypocontractility," 36% with "anal normotension with anal hypocontractility," 67% with "dyssynergia," and 65% with either "rectal hyposensation" or "borderline rectal hyposensation." On univariate analyses, significant differences between the ethnic groups were noted in the rates of "anal hypotension with normal contractility," "combined anal hypotension with anal hypocontractility," and "dyssynergia." In multivariate logistic regression analyses controlling for age, gender, parity, smoking, diabetes, and obesity, the Arab Israeli group remained several times more likely to have "combined anal hypotension and hypocontractibility" compared to the other groups. Conclusions: Ethnicity impacts ARM findings in patients with FI. The reason for this is unclear and future studies on ethnically diverse populations evaluating the clinical relevance of these findings are warranted.

Simultaneous Bilateral Femoral Osteonecrosis in Gaucher Disease.

Gaucher disease (GD) is one of the most common lysosomal storage disorders. Bone complications are the most critical irreversible consequence of GD. Osteonecrosis (ON) of the femoral head inevitably leads to osteoarthritis and may be managed by hip arthroplasty. The introduction and worldwide use of therapeutic agents (specifically enzyme replacement therapies (ERT)) lowered the prevalence of osteonecrosis events per patient. We present the cases of two female patients who sustained simultaneous bilateral femoral head osteonecrosis after receiving ERT for long periods while exposed to concomitant risk factors related to femoral head ON. Both patients suffered severe pain and deterioration of their daily activity capabilities, and thus, were offered bilateral hip arthroplasty. Surgery was performed in both hip joints during the same procedure. The current report highlights several key aspects of femoral head ON in young patients with GD.

The DNA methylome of human vascular endothelium and its use in liquid biopsies.

BACKGROUND: Vascular endothelial cells (VECs) are an essential component of each tissue, contribute to multiple pathologies, and are targeted by important drugs. Yet, there is a shortage of biomarkers to assess VEC turnover. METHODS: To develop DNA methylation-based liquid biopsies for VECs, we determined the methylome of VECs isolated from freshly dissociated human tissues. FINDINGS: A comparison with a human cell-type methylome atlas yielded thousands of loci that are uniquely unmethylated in VECs. These sites are typically gene enhancers, often residing adjacent to VEC-specific genes. We also identified hundreds of genomic loci that are differentially methylated in organotypic VECs, indicating that VECs feeding specific organs are distinct cell types with a stable epigenetic identity. We established universal and lung-specific VEC markers and evaluated their presence in circulating cell-free DNA (cfDNA). Nearly 2.5% of cfDNA in the plasma of healthy individuals originates from VECs. Sepsis, graft versus host disease, and cardiac catheterization are associated with elevated levels of VEC-derived cfDNA, indicative of vascular damage. Lung-specific VEC cfDNA is selectively elevated in patients with chronic obstructive pulmonary disease (COPD) or lung cancer, revealing tissue-specific vascular turnover. CONCLUSIONS: VEC cfDNA biomarkers inform vascular dynamics in health and disease, potentially contributing to early diagnosis and monitoring of pathologies, and assessment of drug activity. FUNDING: This work was supported by the Beutler Research Program, Helmsley Charitable Trust, JDRF, Grail and the DON Foundation (to Y.D.). Y.D holds the Walter & Greta Stiel Chair in heart studies. B.G., R.S., J.M., D.N., T.K., and Y.D. filed patents on cfDNA analysis.

Long-term outcomes of the Nexgen© posterior stabilized knee: minimum 15 year follow-safe and effective.

PURPOSE: Studying long-term survivorship and functional outcomes for specific prostheses is critical for elucidating areas in need of design improvement. This study reports the long-term of the NexGen Posterior Stabilized (PS) Total Knee implant (TKA) (Zimmer Biomet, Warsaw IN) Performed by a single surgeon. METHODS: Data from patients treated with the NexGen PS TKA between January 2003 and December 2005 with a minimal follow-up of 15 years was collected from a prospectively collected database. Survivorship rates and Oxford Knee Scores (OKS) were obtained for those patients available for follow-up. RESULTS: Ninety-five patients met the inclusion criteria during the study period. OKS was available for 44 (46%) patients. Ten patients required revision surgery (10.52%). Implant-specific survivorship of all cases that were reviewed was 98%. Survivorship of implants in patients that we were able to reach, or deceased patients was 93%. The average Oxford Knee Score was 39.1 (14-48. SD ± 7.70) with 48 being the maximal score. CONCLUSION: Despite some concerns about durability of this implant, good longevity and function was demonstrated. At a minimum of 15 years follow-up in this cohort. Given these results design features of this system should be considered for future generations of implants.

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non-muscle-invasive Spectrum.

BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. PATIENT SUMMARY: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.

Serious Bacterial Infections in Young Febrile Infants With Positive Urinalysis Results.

It is unknown whether febrile infants 29 to 60 days old with positive urinalysis results require routine lumbar punctures for evaluation of bacterial meningitis. OBJECTIVE: To determine the prevalence of bacteremia and/or bacterial meningitis in febrile infants ≤60 days of age with positive urinalysis (UA) results. METHODS: Secondary analysis of a prospective observational study of noncritical febrile infants ≤60 days between 2011 and 2019 conducted in the Pediatric Emergency Care Applied Research Network emergency departments. Participants had temperatures ≥38°C and were evaluated with blood cultures and had UAs available for analysis. We report the prevalence of bacteremia and bacterial meningitis in those with and without positive UA results. RESULTS: Among 7180 infants, 1090 (15.2%) had positive UA results. The risk of bacteremia was higher in those with positive versus negative UA results (63/1090 [5.8%] vs 69/6090 [1.1%], difference 4.7% [3.3% to 6.1%]). There was no difference in the prevalence of bacterial meningitis in infants ≤28 days of age with positive versus negative UA results (∼1% in both groups). However, among 697 infants aged 29 to 60 days with positive UA results, there were no cases of bacterial meningitis in comparison to 9 of 4153 with negative UA results (0.2%, difference -0.2% [-0.4% to -0.1%]). In addition, there were no cases of bacteremia and/or bacterial meningitis in the 148 infants ≤60 days of age with positive UA results who had the Pediatric Emergency Care Applied Research Network low-risk blood thresholds of absolute neutrophil count <4 × 103 cells/mm3 and procalcitonin <0.5 ng/mL. CONCLUSIONS: Among noncritical febrile infants ≤60 days of age with positive UA results, there were no cases of bacterial meningitis in those aged 29 to 60 days and no cases of bacteremia and/or bacterial meningitis in any low-risk infants based on low-risk blood thresholds in both months of life. These findings can guide lumbar puncture use and other clinical decision making.

Video Capsule Endoscopy Has a Minor Long-term Therapeutic Impact on Patients with Iron Deficiency Anemia.

BACKGROUND: One of the main causes of iron deficiency anemia (IDA) is chronic gastrointestinal blood loss. The use of video capsule endoscopy (VCE) after negative bidirectional endoscopy in patients with IDA is controversial. OBJECTIVES: To evaluate the effect of VCE in the management and long-term outcomes of IDA patients. METHODS: A retrospective case-control study was performed on all patients with IDA undergoing VCE over a 5-year period. We compared those with positive findings on VCE to those with normal findings. All participants previously underwent a negative bidirectional endoscopy. RESULTS: We performed 199 VCE examinations; median follow-up time was 4 years (IQR 2-5). Positive findings were identified in 66 patients (diagnostic yield 33.2%). Double balloon enteroscopy or push enteroscopy was performed in eight patients (18.6%); only one was therapeutic. The main therapy in both groups was iron supplementation. There were no significant differences in iron treatment before and after VCE in each group and between groups. Anemia improved in both groups. There was no difference in the level of hemoglobin change between the groups during each year of follow-up compared to the baseline level prior to VCE. Anemia resolved in 15 patients (35%) in the positive VCE group and in 19 (45%) in the negative VCE group (P = 0.33). CONCLUSIONS: Positive findings on VCE led to subsequent endoscopic interventions only in a small percentage of patients with IDA. Anemia improved and resolved equally whether or not there were VCE findings. The main intervention that appears to help IDA is iron supplementation.