Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).

Application of entropy and signal energy for ultrasound-based classification of three-dimensional printed polyetherketoneketone components.

This paper describes a preliminary method for the classification of annealed and unannealed polyetherketoneketone (PEKK) components manufactured using a material extrusion three-dimensional (3D) printing process. PEKK is representative of a class of high-performance thermoplastics that are increasingly employed as feedstocks for use in 3D printing. PEKK components may be used continuously at elevated temperatures, are chemically resistant, and able to withstand large mechanical loads. These properties render PEKK suitable as a metal component replacement in aerospace applications, high-temperature industrial applications, and surgical implants. The structure of PEKK is semi-crystalline with the specific crystallinity correlating to the final properties during application, making determination of this property crucial. This study compares three different signal processing techniques intended to distinguish annealed (high crystallinity) from unannealed (low crystallinity) components using backscattered ultrasound. The first is energy-based and is unable to detect annealing. The second two are based on different entropies of the backscattered signal: a limiting form of Renyi's entropy and a limiting form of joint entropy. The joint entropy values for the annealed and unannealed specimens fall into two non-overlapping intervals and have a statistical separation of two standard deviations.

Expert Consensus for Early Onset Scoliosis Surgery.

BACKGROUND: Despite a validated classification system, high-quality multicenter research databases (CSSG/GSSG), and a recent proliferation in publications, early-onset scoliosis (EOS) surgeons have no consensus on standards for surgical treatment. The 21st-century revolution in EOS care has only accelerated, with the arrival of a classification system, magnetically controlled growing rod, nusinersen, and improved nonoperative care (Mehta or Risser casting and compliance-monitored braces). This dizzying pace of change may have outstripped our ability to develop best-practice standards for EOS surgical indications. To learn where consensus is best (and worst) at this moment, we surveyed EOS world thought-leaders on a collection of representative cases. METHODS: A 6-case survey was constructed and sent to 20 EOS world thought-leaders. The cases were selected to be representative of the major treatment categories: idiopathic, neuromuscular, syndromic, congenital, thoracic dysplasia, and spinal muscular atrophy (specifically to assess the impact of nusinersen and parasol deformity on surgical planning). Respondents were queried regarding treatment with specific attention to instrumentation and construct when surgery was selected. Responses regarding surgical timing and technique were analyzed for consensus (defined as >80%). χ analysis was performed to evaluate for differences in treatment preferences based on years of experience. RESULTS: The survey response was 100%. Clinical experience ranged from 8 to 40 years (average 23.9 y). There was no consensus on any case. The greatest variability was on the congenital case; the closest to consensus was on the spinal muscular atrophy case. Three or more approaches were selected for all 6 cases; >4 approaches were selected for 5 cases. There is a trend towards screw fixation for proximal anchors. The management of thoracic dysplasia and parasol deformity is far from consensus. CONCLUSION: The lack of consensus for surgical treatment of 6 representative EOS cases demands a renewed effort and commitment to develop best-practice guidelines based on multicenter outcome data. LEVEL OF EVIDENCE: Level V-Expert Opinion.

Entropy vs. Energy Waveform Processing: A Comparison Based on the Heat Equation.

Virtually all modern imaging devices collect electromagnetic or acoustic waves and use the energy carried by these waves to determine pixel values to create what is basically an "energy" picture. However, waves also carry "information", as quantified by some form of entropy, and this may also be used to produce an "information" image. Numerous published studies have demonstrated the advantages of entropy, or "information imaging", over conventional methods. The most sensitive information measure appears to be the joint entropy of the collected wave and a reference signal. The sensitivity of repeated experimental observations of a slowly-changing quantity may be defined as the mean variation (i.e., observed change) divided by mean variance (i.e., noise). Wiener integration permits computation of the required mean values and variances as solutions to the heat equation, permitting estimation of their relative magnitudes. There always exists a reference, such that joint entropy has larger variation and smaller variance than the corresponding quantities for signal energy, matching observations of several studies. Moreover, a general prescription for finding an "optimal" reference for the joint entropy emerges, which also has been validated in several studies.

Isolated optic nerve, chiasm, and tract involvement in Bing-Neel Syndrome.

Central nervous system infiltration of Waldenström's macroglobulinemia is referred to as Bing-Neel Syndrome. We describe 2 patients whose clinical presentation was due to isolated involvement of the anterior visual pathways. The mechanism of visual failure in Bing-Neel Syndrome may involve both infiltrative and autoimmune processes.

Development of a Real-time Force-based Algorithm for Infusion Failure Detection.

BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is a common treatment option for people with diabetes (PWD), but insulin infusion failures pose a significant challenge, leading to hyperglycemia, diabetes burnout, and increased hospitalizations. Current CSII pumps' occlusion alarm systems are limited in detecting infusion failures; therefore, a more effective detection method is needed. METHODS: We conducted five preclinical animal studies to collect data on infusion failures, utilizing both insulin and non-insulin boluses. Data were captured using in-line pressure and flow rate sensors, with additional force data from CSII pumps' onboard sensors in one study. A novel classifier model was developed using this dataset, aimed at detecting different types of infusion failures through direct utilization of force sensor data. Performance was compared against various occlusion alarm thresholds from commercially available CSII pumps. RESULTS: The testing dataset included 251 boluses. The Bagging classifier model showed the highest performance metrics among the models tested, exhibiting high accuracy (96%), sensitivity (94%), and specificity (98%), with lower false-positive and false-negative rate compared with traditional occlusion alarm pressure thresholds. CONCLUSIONS: Our study developed a novel non-threshold classifier that outperforms current occlusion alarm systems in CSII pumps in detecting infusion failures. This advancement has the potential to reduce the risk of hyperglycemia and hospitalizations due to undetected infusion failures, offering a more reliable and effective CSII therapy for PWD. Further studies involving human participants are recommended to validate these findings and assess the classifier's performance in a real-world setting.

Multicenter Evaluation of Ultra-Rapid Lispro Insulin with Control-IQ Technology in Adults, Adolescents, and Children with Type 1 Diabetes.

Objective: To evaluate the safety and explore the efficacy of use of ultra-rapid lispro (URLi, Lyumjev) insulin in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology in children, teenagers, and adults living with type 1 diabetes (T1D). Methods: At 14 U.S. diabetes centers, youth and adults with T1D completed a 16-day lead-in period using lispro in a t:slim X2 insulin pump with Control-IQ 1.5 technology, followed by a 13-week period in which URLi insulin was used in the pump. Results: The trial included 179 individuals with T1D (age 6-75 years). With URLi, 1.7% (3 participants) had a severe hypoglycemia event over 13 weeks attributed to override boluses or a missed meal. No diabetic ketoacidosis events occurred. Two participants stopped URLi use because of infusion-site discomfort, and one stopped after developing a rash. Mean time 70-180 mg/dL increased from 65% ± 15% with lispro to 67% ± 13% with URLi (P = 0.004). Mean insulin treatment satisfaction questionnaire score improved from 75 ± 13 at screening to 80 ± 11 after 13 weeks of URLi use (mean difference = 6; 95% confidence interval 4-8; P < 0.001), with the greatest improvement reported for confidence avoiding symptoms of high blood sugar. Mean treatment-related impact measure-diabetes score improved from 74 ± 12 to 80 ± 12 (P < 0.001), and mean TRIM-Diabetes Device (score improved from 82 ± 11 to 86 ± 12 (P < 0.001). Conclusions: URLi use in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology was safe for adult and pediatric participants with T1D, with quality-of-life benefits of URLi use perceived by the study participants. Clinicaltrials.gov registration: NCT05403502.

Orthopaedic injuries from deer stands and their functional outcomes.

Hunters who fall from deer stands can sustain a variety of injuries. A retrospective review was conducted at a single institution to gauge the experience in treating patients injured in falls from deer stands from 2002 to 2008. Medical records were analyzed for patient demographics, tree stand characteristics, and injury details. Patients were contacted to complete a SF-12 health survey to assess their functional outcome following their injuries. Of the 30 patients who sustained a fracture, an average of 2.08 fractures were sustained per patient. Sixteen patients sustained a spinal column fracture, and four of these sustained a spinal cord injury. Twenty-one patients underwent at least one surgical procedure by the trauma surgery (two), neurosurgery (four), or orthopaedic surgery (15) teams. The importance of understanding deer stand instructions should be emphasized during hunting education classes, and all hunters should follow safe hunting recommendations pertaining to firearms and tree stands.

Frequency and Detection of Insulin Infusion Site Failure in the Type 1 Diabetes Exchange Online Community.

Insulin infusion site (IIS) failures are a weakness in insulin pump therapy. We examined experience with IIS failures among U.S. individuals with diabetes on insulin pump through survey distributed to the T1D Exchange Online Community. Demographic factors, IIS characteristics, and diabetes-related perceptions were assessed by logistic regression to determine odds of higher (≥1 per month) or lower (<1 per month) reported IIS failure frequency. IIS failures were common; 41.4% reported ≥1 per month. IIS failure is usually detected through development of hyperglycemia rather than pump alarm. No assessed demographic factor or IIS characteristic was predictive; however, higher odds of ≥1 failure per month were associated with feelings of burnout (odds ratios [OR] 1.489 [1.024, 2.165]) and considering pump discontinuation (OR 2.233 [1.455, 3.427]). IIS failures are frequent and unpredictable, typically require hyperglycemia for detection, and are associated with negative perceptions. More should be done toward preventing IIS failures and/or detecting them sooner.

Automated Insulin Delivery with Remote Real-Time Continuous Glucose Monitoring for Hospitalized Patients with Diabetes: A Multicenter, Single-Arm, Feasibility Trial.

Introduction: Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. Research Design and Methods: In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units. Primary endpoints included the proportion of time in automated mode and percent time-in-range (TIR 70-180 mg/dL) among participants with >48 h of CGM data. Safety endpoints included incidence of severe hypoglycemia and diabetes-related ketoacidosis (DKA). Additional glycemic endpoints, CGM accuracy, and patient satisfaction were also explored. Results: Twenty-two participants were enrolled; 18 used the system for a total of 96 days (mean 5.3 ± 3.1 days per patient), and 16 had sufficient CGM data required for analysis. Median percent time in automated mode was 95% (interquartile range 92%-98%) for the 18 system users, and the 16 participants with >48 h of CGM data achieved an overall TIR of 68% ± 16%, with 0.17% ± 0.3% time <70 mg/dL and 0.06% ± 0.2% time <54 mg/dL. Sensor mean glucose was 167 ± 21 mg/dL. There were no DKA or severe hypoglycemic events. All participants reported satisfaction with the system at study end. Conclusions: The use of AID with a disposable tubeless patch-pump along with remote real-time CGM is feasible in the hospital setting. These results warrant further investigation in randomized trials.

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide for Peripheral T Cell Lymphoma: The Importance of Graft Source.

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus host-disease (GVHD) prophylaxis has revolutionized allogeneic blood or marrow transplantation (alloBMT), but there is limited published experience in peripheral T cell lymphoma (PTCL). We sought to assess outcomes in patients with PTCL who underwent alloBMT with PTCy. We reviewed the charts of all adult patients age ≥18 years who underwent alloBMT with nonmyeloablative conditioning and PTCy-based GVHD prophylaxis at the Sidney Kimmel Comprehensive Cancer Center between January 2004 and December 2020. Sixty-five patients were identified. The median age was 59 years (range, 24 to 75 years). Lymphoma histology included PTCL not otherwise specified (n = 24), anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n = 14), angioimmunoblastic T cell lymphoma (n = 7), enteropathy-associated T cell lymphoma (n = 6), hepatosplenic T cell lymphoma (n = 4), and others (n = 10). Eleven patients were in first complete remission (17%); the remaining patients were in first partial remission or underwent salvage therapy to at least PR prior to transplantation. Forty-eight patients underwent alloBMT from a haploidentical related donor (74%), 10 from a fully matched donor (15%), and 7 from a mismatched unrelated donor (11%). All patients received fludarabine, cyclophosphamide, and total body irradiation (TBI). The graft source was bone marrow (BM) in 46 patients (71%) and peripheral blood (PB) in 19 patients (29%); all patients in the BM cohort received 200 cGy TBI, and most patients in the PB cohort (15 of 19) received 400 cGy TBI. GVHD prophylaxis comprised PTCy, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. With a median follow-up of 2.8 years (range, 290 days to 14.2 years), the 2-year progression-free survival (PFS) for the entire cohort was 49% (95% confidence interval [CI], 38% to 64%), and the 2-year overall survival (OS) was 55% (95% CI, 44% to 69%). Outcomes were significantly improved in those receiving PB compared to those receiving BM, including a 2-year PFS of 79% (95% CI 63% to 100%) versus 39% (95% CI, 27% to 56%), 2-year OS of 84% (95% CI, 69% to 100%) versus 46% (95% CI, 33% to 63%), and 1-year cumulative incidence of relapse of 5% (95% CI, 0 to 16%) versus 33% (95% CI, 19% to 46%), with no difference in GVHD and nonrelapse mortality. AlloBMT with PTCy is safe and well-tolerated in patients with PTCL. Our data suggest that increasing the TBI dose to 400 cGy and using PB allografts may offer improved disease control and better survival outcomes, though additional studies are needed to confirm these findings.

Angiogenesis imaging with vascular-constrained particles: the why and how.

Angiogenesis is a keystone in the treatment of cancer and potentially many other diseases. In cancer, first-generation antiangiogenic therapeutic approaches have demonstrated survival benefit in subsets of patients, but their high cost and notable adverse side effect risk have fueled alternative development efforts to personalize patient selection and reduce off-target effects. In parallel, rapid advances in cost-effective genomic profiling and sensitive early detection of high-risk biomarkers for cancer, atherosclerosis, and other angiogenesis-related pathologies will challenge the medical imaging community to identify, characterize, and risk stratify patients early in the natural history of these disease processes. Conventional diagnostic imaging techniques were not intended for such sensitive and specific detection, which has led to the emergence of novel noninvasive biomedical imaging approaches. The overall intent of molecular imaging is to achieve greater quantitative characterization of pathologies based on microanatomical, biochemical, or functional assessments; in many approaches, the capacity to deliver effective therapy, e.g., antiangiogenic therapy, can be combined. Agents with both diagnostic and therapy attributes have acquired the moniker "theranostics." This review will explore biomedical imaging options being pursued to better segment and treat patients with angiogenesis-influenced disease using vascular-constrained contrast platform technologies.

Open Reduction and Suture Fixation of Acute Sternoclavicular Fracture-Dislocations in Children.

BACKGROUND: Acute sternoclavicular fracture-dislocation is associated with high-energy trauma and is being increasingly recognized in children1. These injuries are associated with compression of mediastinal structures and can be life-threatening1. The management of acute sternoclavicular fracture-dislocation includes closed reduction or open surgical stabilization; however, limited success is reported with closed reduction2,3. To our knowledge, there are no detailed descriptions of open reduction and suture fixation of acute sternoclavicular fracture-dislocation in children. DESCRIPTION: Following diagnosis of acute sternoclavicular fracture-dislocation, the timing of surgical treatment is determined according to several patient and surgical factors. Among patients with hemodynamic instability, respiratory compromise, or evidence of asymmetric perfusion, surgical treatment is needed on an emergency basis. In the absence of these factors, surgical treatment can be performed on an urgent basis. It is important to communicate with vascular or thoracic surgeons prior to proceeding to the operating room because of the rare case in which advanced surgical access or vascular repair is required. In the operating room, general anesthesia and large-bore intravenous access are required. Patients are positioned supine on a radiolucent table, and a small bump is placed between the scapulae to elevate the medial aspect of the clavicle. The contralateral sternoclavicular joint and medial aspect of the clavicle should be prepared into the sterile field, as well as both sides of the groin in case vascular access is needed. A 6 to 8-cm incision is centered on the medial aspect of the clavicle, extending to the manubrium. Standard dissection to the clavicle is performed, and care is taken to maintain the integrity of the sternoclavicular ligament complex. Circumferential dissection of the medial clavicular metaphysis is usually required in order to mobilize the dislocated fragment. Reduction of the physeal fracture usually requires axial traction and extension of the ipsilateral shoulder with the aid of a reduction clamp on the medial clavicular metaphysis. In some cases, a Freer elevator can be placed between the metaphysis and epiphysis to shoehorn the clavicle from posterior to anterior. Once reduced, the fracture-dislocation is usually stable; however, the reduction is augmented with suture fixation. The sternoclavicular joint capsule should be repaired if disrupted, and the incision should be closed in layers. Postoperatively, the arm is placed in a sling, and range of motion is commenced at 4 weeks. ALTERNATIVES: Alternative management of acute sternoclavicular fracture-dislocation includes closed reduction, plate fixation4, and ligament reconstruction5. RATIONALE: In our experience, closed reduction is often unsuccessful, which is consistent with the experiences reported by other authors2,3. In addition, suture fixation is sufficient and plate fixation is not required because this injury is relatively stable following reduction. Lastly, ligament reconstruction with use of autograft or allograft may be indicated but is more relevant in chronic cases with injury or attenuation of the sternoclavicular ligament complex. Open reduction allows for direct visualization of the fracture reduction, and suture fixation allows for increased stability without the need for hardware or secondary surgical procedures. EXPECTED OUTCOMES: We expect patients to achieve full range of motion and strength without any joint instability as reported by Waters et al.3. IMPORTANT TIPS: There is an inherent risk of vascular injury with open reduction and suture fixation. This risk is mitigated with perioperative planning and consultation with vascular or thoracic surgeons. General surgeons should always be available when these procedures are performed in case of vascular issues or emergencies.It is sometimes difficult to reduce the dislocation, but additional maneuvers allow for controlled reduction of the displaced clavicle, such as using a Freer elevator and serrated clamp.Assessing fracture reduction can be difficult intraoperatively. Including the contralateral sternoclavicular joint in the sterile surgical field can be helpful in assessing fracture reduction and osseous contour.

Checking the Checkpoint Inhibitors: A Case of Autoimmune Diabetes After PD-1 Inhibition in a Patient with HIV.

Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a known immune-related adverse event (irAE) following treatment with programmed cell death protein 1 (PD-1), with a reported 0.9% incidence. We hereby present the first case, to our knowledge, of ICI-DM following ICI use in a human immunodeficiency virus (HIV) patient. In this case, a 48-year-old man with HIV stable on highly active antiretroviral therapy (HAART) was diagnosed with Hodgkin lymphoma and initiated treatment with the PD-1 inhibitor nivolumab. His lymphoma achieved complete response after 5 months. However, at month 8, he reported sudden polydipsia and polyuria. Labs revealed a glucose level of 764 mg/dL and glycated hemoglobin A1c (HbA1c) of 7.1%. Low C-peptide and elevated glutamic acid decarboxylase 65 (GAD65) antibody levels confirmed autoimmune DM, and he was started on insulin. Major histocompatibility complex class II genetic analysis revealed homozygous HLA DRB1*03-DQA1*0501-DQB1*02 (DR3-DQ2), which is a known primary driver of genetic susceptibility to type 1 DM. Autoimmune DM has been reported as an ICI-associated irAE. However, patients with immunocompromising conditions such as HIV are usually excluded from ICI trials. Therefore, little is known about such irAEs in this population. In this case, risk of ICI-DM as an irAE was likely increased by several factors including family history, a high-risk genetic profile, islet-related immunologic abnormalities, active lymphoma, and HIV infection with a possible immune reconstitution event. Clinicians should maintain a high index of suspicion for development of irAEs associated with ICI, particularly as use of these therapies broadens. Thorough investigation for presence of higher-risk features should be conducted and may warrant inclusion of pre-therapy genetic and/or autoantibody screening.

Percutaneous Pinning of Pediatric Proximal Humeral Fractures.

BACKGROUND: Proximal humeral fractures are relatively common in pediatric patients. These injuries are usually treated nonoperatively in younger children or children with minimally displaced fractures. However, closed reduction or open reduction followed by percutaneous pinning is recommended for older children with displaced fractures. Percutaneous pinning has several advantages, but there are limited reports of a safe and reliable surgical technique in the literature. DESCRIPTION: Patients are positioned in a modified beach-chair position to allow orthogonal imaging. The injured extremity is draped free from the remainder of the body. Closed reduction, which comprises a combination of traction, abduction, and rotation, is attempted. Internal or external rotation may be required, depending on the fracture line and deforming forces. If an anatomic closed reduction cannot be obtained, a block to reduction should be suspected and open reduction should be performed via a deltopectoral approach. Once the fracture is reduced, two 2.5-mm threaded Kirschner wires from the small external fixator set are used to percutaneously fix the fracture. Any small external fixator set can be used, and if not available, individual threaded wires of similar size can be used. Alternatively, Kirschner wires can be advanced to the fracture site prior to reduction and then advanced into the humeral epiphysis once the fracture is reduced. Care is taken to avoid the axillary nerve, which is reliably within 6 cm of the anterolateral aspect of the acromion, and wires are placed distal to this site. Once pin position has been confirmed radiographically, the construct is secured with pin-to-pin clamps to improve rigidity and further decrease the risk of pin migration. A soft dressing and shoulder immobilizer are placed postoperatively. Patients are followed with biweekly radiographs, and pins are removed in the outpatient office or under conscious sedation at 4 weeks. Leaving pins for a longer period may increase the risk of skin irritation and potentially infection. ALTERNATIVES: Alternatives to closed reduction or open reduction and percutaneous pinning include nonoperative management and elastic intramedullary nailing. Nonoperative treatment is a reliable option for most patients. However, it is not suitable for older children with severely displaced fractures because of diminished remodeling potential. Elastic intramedullary nailing is a good option for distal fractures. However, it is not suitable for proximal fractures, and it has been associated with longer operative times and more blood loss than percutaneous pinning. It also requires a second procedure. RATIONALE: This procedure allows for anatomic fixation of proximal humeral fractures and provides a rigid construct to maintain reduction. It is not technically challenging, requires limited postoperative immobilization, and decreases the risk of a second general anesthetic.

Budesonide treatment for microscopic colitis from immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (CPIs) are effective against a variety of malignancies but can be limited by inflammatory toxicities such as enterocolitis. Enterocolitis is typically treated with systemically active glucocorticoids. Endoscopy can stratify patients by the severity of mucosal inflammation, including identifying patients with colitis in the absence of visible mucosal changes: microscopic colitis. Whether patients with CPI microscopic colitis could be managed differently from colitis with more severe mucosal involvement is unclear. The objective of this study was to describe outcomes in CPI microscopic colitis focusing on the response to first line treatment with budesonide. METHODS: We evaluated data from a retrospective cohort from a single-center large academic hospital. The participants were all adult patients evaluated by endoscopy for suspected CPI enterocolitis between 3/2017 and 3/2019. The exposures were: Mayo Endoscopic Score (range 0-3). The subset was: oral budesonide, maximum dose 12 mg daily, administered minimum of 5 weeks. The main outcomes and measures were: Primary: time from first CPI exposure to first glucocorticoid use; use of systemic glucocorticoids; time from symptom onset to resolution; continuation of CPI therapy; number of additional CPI infusions received. Secondary: admissions for symptom control; novel irAE development; need for second-line immunosuppression; oncologic outcomes. RESULTS: We identified 38 patients with biopsy confirmed CPI enterocolitis, 13 in the microscopic colitis cohort, and 25 in the non-microscopic colitis cohort. Budesonide use was higher in the microscopic colitis cohort (12/13 vs 3/25, p < 0.001), and systemic glucocorticoid use was higher in non-microscopic colitis (22/25 vs. 3/13, p < 0.001). Time from symptom onset to resolution did not differ. Microscopic colitis patients more frequently remained on CPI after developing (entero)colitis (76.9% vs 16.0%, p < 0.001). Microscopic colitis patients tolerating further CPI received, on average, 4.2 CPI infusions more than non-microscopic colitis patients tolerating CPI (5.8 vs 1.6, p = 0.03). Microscopic colitis was associated with increased time-to-treatment-failure (HR 0.30, 95% CI 0.14-0.66) and progression-free survival (HR 0.22, 95% CI 0.07-0.70). CONCLUSIONS: Gastrointestinal mucosal inflammation without visible mucosal injury is a distinct, prevalent CPI enterocolitis subset that can be diagnosed by endoscopy. First-line budesonide appears effective in controlling "microscopic colitis" symptoms and prolonging immunotherapy duration. These findings present a compelling rationale for routine endoscopic evaluation of suspected CPI enterocolitis and suggest an alternative glucocorticoid-sparing treatment strategy for a subset of such patients.