Spectrum Health

The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment.

BACKGROUND: In patients with symptomatic paroxysmal atrial fibrillation that has not responded to medication, catheter ablation is more effective than antiarrhythmic drug therapy for maintaining sinus rhythm. However, the safety and efficacy of cryoballoon ablation as initial first-line therapy have not been established. METHODS: We performed a multicenter trial in which patients 18 to 80 years of age who had paroxysmal atrial fibrillation for which they had not previously received rhythm-control therapy were randomly assigned (1:1) to receive treatment with antiarrhythmic drugs (class I or III agents) or pulmonary vein isolation with a cryoballoon. Arrhythmia monitoring included 12-lead electrocardiography conducted at baseline and at 1, 3, 6, and 12 months; patient-activated telephone monitoring conducted weekly and when symptoms were present during months 3 through 12; and 24-hour ambulatory monitoring conducted at 6 and 12 months. The primary efficacy end point was treatment success (defined as freedom from initial failure of the procedure or atrial arrhythmia recurrence after a 90-day blanking period to allow recovery from the procedure or drug dose adjustment, evaluated in a Kaplan-Meier analysis). The primary safety end point was assessed in the ablation group only and was a composite of several procedure-related and cryoballoon system-related serious adverse events. RESULTS: Of the 203 participants who underwent randomization and received treatment, 104 underwent ablation, and 99 initially received drug therapy. In the ablation group, initial success of the procedure was achieved in 97% of patients. The Kaplan-Meier estimate of the percentage of patients with treatment success at 12 months was 74.6% (95% confidence interval [CI], 65.0 to 82.0) in the ablation group and 45.0% (95% CI, 34.6 to 54.7) in the drug-therapy group (P<0.001 by log-rank test). Two primary safety end-point events occurred in the ablation group (Kaplan-Meier estimate of the percentage of patients with an event within 12 months, 1.9%; 95% CI, 0.5 to 7.5). CONCLUSIONS: Cryoballoon ablation as initial therapy was superior to drug therapy for the prevention of atrial arrhythmia recurrence in patients with paroxysmal atrial fibrillation. Serious procedure-related adverse events were uncommon. (Supported by Medtronic; STOP AF First ClinicalTrials.gov number, NCT03118518.).

In recent years, increasing numbers of children have been diagnosed with bipolar disorder. In some cases, children with unstable mood clearly meet current diagnostic criteria for bipolar disorder, and in others, the diagnosis is unclear. Severe mood dysregulation is a syndrome defined to capture the symptomatology of children whose diagnostic status with respect to bipolar disorder is uncertain, that is, those who have severe, nonepisodic irritability and the hyperarousal symptoms characteristic of mania but who lack the well-demarcated periods of elevated or irritable mood characteristic of bipolar disorder. Levels of impairment are comparable between youths with bipolar disorder and those with severe mood dysregulation. An emerging literature compares children with severe mood dysregulation and those with bipolar disorder in longitudinal course, family history, and pathophysiology. Longitudinal data in both clinical and community samples indicate that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders, but not bipolar disorder, in adulthood. Data also suggest that youths with severe mood dysregulation have lower familial rates of bipolar disorder than do those with bipolar disorder. While youths in both patient groups have deficits in face emotion labeling and experience more frustration than do normally developing children, the brain mechanisms mediating these pathophysiologic abnormalities appear to differ between the two patient groups. No specific treatment for severe mood dysregulation currently exists, but verification of its identity as a syndrome distinct from bipolar disorder by further research should include treatment trials.

Objective: This retrospective case series reviews clinico-pathologic findings of two patients with seizures provoked by e-cigarette use. Background: The health consequences of e-cigarette use (vaping) have recently garnered significant media attention, most notably for numerous reports of severe pulmonary pathology. There are scattered case reports of vape-induced seizures, but thus far there have been little objective data supporting this association. Design/Methods: A retrospective case series of two patients at an urban Level IV Epilepsy Center were reviewed. Demographics and relevant clinco-pathologic data including invasive electroencephalography (EEG) data from an implanted RNS are noted Results: The first case is of an 18 year-old female with no significant medical history presented with three isolated incidents of reported generalized seizures, all occurring within hours of vaping. Comprehensive examination, laboratory data, neuroimaging, and EEG data revealed no identifiable cause other than e-cigarette use, and seizures abated following cessation of e-cigarette use. The second case is of a 32 year-old male with intractable bitemporal epilepsy since age 9 on multiple anti-seizure medications, status post RNS placement, in whom RNS alerted clinicians to increased frequency of seizures. Although there are other confounders, this paper reviews the details on how seizure counts changed while monitored on RNS during the extended period of months when vaping continued and was subsequently discontinued. Conclusions: Our case series identifies two patients in whom seizures were triggered by vaping. This work supports the association with objective EEG/electrocorticographic data from an implanted RNS(Responsive NeuroStimulator). Further research is needed into the health consequences of e-cigarette use since vaping poses a major health crisis in the US and the comprehensive pathology induced or involved remains unknown at present. Disclosure: Dr. Oster has received research support from Eisai, Biogen. Dr. Tatum has nothing to disclose. Dr. Monigan has nothing to disclose. Dr. Kryzanski has nothing to disclose.

The broad spectrum kinase inhibitor sunitinib is a first-line therapy for advanced clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer. Unfortunately, most patients develop sunitinib resistance and progressive disease after about 1 year of treatment. In this study, we evaluated the mechanisms of resistance to sunitinib to identify the potential tactics to overcome it. Xenograft models were generated that mimicked clinical resistance to sunitinib. Higher microvessel density was found in sunitinib-resistant tumors, indicating that an escape from antiangiogenesis occurred. Notably, escape coincided with increased secretion of interleukin-8 (IL-8) from tumors into the plasma, and coadministration of an IL-8 neutralizing antibody resensitized tumors to sunitinib treatment. In patients who were refractory to sunitinib treatment, IL-8 expression was elevated in ccRCC tumors, supporting the concept that IL-8 levels might predict clinical response to sunitinib. Our results reveal IL-8 as an important contributor to sunitinib resistance in ccRCC and a candidate therapeutic target to reverse acquired or intrinsic resistance to sunitinib in this malignancy.

We evaluated a brief multiple-stimulus preference assessment within the context of an early intervention program for 3 children who had been diagnosed with autism. Subsequent curriculum-based reinforcer evaluations confirmed the predictions of the preference assessments. In addition, eight additional preference assessments that were conducted over a period of 1 month indicated generally stable preferences for 2 of the 3 participants.

Pancreatic cancer is one of the leading causes for cancer-related deaths in the United States. Majority of patients present with unresectable or metastatic disease. For those that present with localized disease, a multidisciplinary approach is necessary to maximize survival and optimize outcomes. The quality and safety of surgery for pancreatic cancer have improved in recent years with increasing adoption of minimally invasive techniques and surgical adjuncts. Systemic chemotherapy has also evolved to impact survival. It is now increasingly being utilized in the neoadjuvant setting, often with concomitant radiation. Increased utilization of genomic testing in metastatic pancreatic cancer has led to better understanding of their biology, thereby allowing clinicians to consider potential targeted therapies. Similarly, targeted agents such as PARP inhibitors and immune checkpoint- inhibitors have emerged with promising results. In summary, pancreatic cancer remains a disease with poor long-term survival. However, recent developments have led to improved outcomes and have changed practice in the past decade. This review summarizes current practices in pancreatic cancer treatment and the milestones that brought us to where we are today, along with emerging therapies.

The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population: 1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF . These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations. 2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF . These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.

Trials of coronavirus disease 2019 (COVID-19) vaccination included limited numbers of children, so they may not have detected rare but important adverse events in this population. We report 7 cases of acute myocarditis or myopericarditis in healthy male adolescents who presented with chest pain all within 4 days after the second dose of Pfizer-BioNTech COVID-19 vaccination. Five patients had fever around the time of presentation. Acute COVID-19 was ruled out in all 7 cases on the basis of negative severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction test results of specimens obtained by using nasopharyngeal swabs. None of the patients met criteria for multisystem inflammatory syndrome in children. Six of the 7 patients had negative severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody assay results, suggesting no previous infection. All patients had an elevated troponin. Cardiac MRI revealed late gadolinium enhancement characteristic of myocarditis. All 7 patients resolved their symptoms rapidly. Three patients were treated with nonsteroidal antiinflammatory drugs only, and 4 received intravenous immunoglobulin and corticosteroids. In this report, we provide a summary of each adolescent's clinical course and evaluation. No causal relationship between vaccine administration and myocarditis has been established. Continued monitoring and reporting to the US Food and Drug Administration Vaccine Adverse Event Reporting System is strongly recommended.

Importance: In young febrile infants, serious bacterial infections (SBIs), including urinary tract infections, bacteremia, and meningitis, may lead to dangerous complications. However, lumbar punctures and hospitalizations involve risks and costs. Clinical prediction rules using biomarkers beyond the white blood cell count (WBC) may accurately identify febrile infants at low risk for SBIs. Objective: To derive and validate a prediction rule to identify febrile infants 60 days and younger at low risk for SBIs. Design, Setting, and Participants: Prospective, observational study between March 2011 and May 2013 at 26 emergency departments. Convenience sample of previously healthy febrile infants 60 days and younger who were evaluated for SBIs. Data were analyzed between April 2014 and April 2018. Exposures: Clinical and laboratory data (blood and urine) including patient demographics, fever height and duration, clinical appearance, WBC, absolute neutrophil count (ANC), serum procalcitonin, and urinalysis. We derived and validated a prediction rule based on these variables using binary recursive partitioning analysis. Main Outcomes and Measures: Serious bacterial infection, defined as urinary tract infection, bacteremia, or bacterial meningitis. Results: We derived the prediction rule on a random sample of 908 infants and validated it on 913 infants (mean age was 36 days, 765 were girls [42%], 781 were white and non-Hispanic [43%], 366 were black [20%], and 535 were Hispanic [29%]). Serious bacterial infections were present in 170 of 1821 infants (9.3%), including 26 (1.4%) with bacteremia, 151 (8.3%) with urinary tract infections, and 10 (0.5%) with bacterial meningitis; 16 (0.9%) had concurrent SBIs. The prediction rule identified infants at low risk of SBI using a negative urinalysis result, an ANC of 4090/µL or less (to convert to ×109 per liter, multiply by 0.001), and serum procalcitonin of 1.71 ng/mL or less. In the validation cohort, the rule sensitivity was 97.7% (95% CI, 91.3-99.6), specificity was 60.0% (95% CI, 56.6-63.3), negative predictive value was 99.6% (95% CI, 98.4-99.9), and negative likelihood ratio was 0.04 (95% CI, 0.01-0.15). One infant with bacteremia and 2 infants with urinary tract infections were misclassified. No patients with bacterial meningitis were missed by the rule. The rule performance was nearly identical when the outcome was restricted to bacteremia and/or bacterial meningitis, missing the same infant with bacteremia. Conclusions and Relevance: We derived and validated an accurate prediction rule to identify febrile infants 60 days and younger at low risk for SBIs using the urinalysis, ANC, and procalcitonin levels. Once further validated on an independent cohort, clinical application of the rule has the potential to decrease unnecessary lumbar punctures, antibiotic administration, and hospitalizations.

PURPOSE: Factors that determine renal function after partial nephrectomy are not well-defined, including the impact of cold vs warm ischemia, and the relative importance of modifiable and nonmodifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing partial nephrectomy. MATERIALS AND METHODS: From 1980 to 2009, 660 partial nephrectomies were performed at 4 centers for tumor in a solitary functioning kidney under cold (300) or warm (360) ischemia. Data were collected in institutional review board approved registries and followup averaged 4.5 years. Preoperative and postoperative glomerular filtration rates were estimated via the Chronic Kidney Disease-Epidemiology Study equation. RESULTS: At 3 months after partial nephrectomy median glomerular filtration rate decreased by equivalent amounts with cold or warm ischemia (21% vs 22%, respectively, p = 0.7), although median cold ischemic times were much longer (45 vs 22 minutes respectively, p <0.001). On multivariable analyses increasing age, larger tumor size, lower preoperative glomerular filtration rate and longer ischemia time were associated with decreased postoperative glomerular filtration rate (p <0.05). When percentage of parenchyma spared was incorporated into the analysis, this factor and preoperative glomerular filtration rate proved to be the primary determinants of ultimate renal function, and duration of ischemia lost statistical significance. CONCLUSIONS: This nonrandomized, comparative study suggests that within the relatively strict parameters of conventional practice, ie predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after partial nephrectomy. Long-term renal function after partial nephrectomy is determined primarily by the quantity and quality of renal parenchyma preserved, although type and duration of ischemia remain the most important modifiable factors, and warrant further study.

OBJECTIVE: Most patients with epithelial ovarian cancer who are alive at 5 years have active disease. Thus, 10-year survival rather than 5-year survival may be a more appropriate endpoint. Relative survival adjusts for the general survival of the United States population for that race, sex, age, and date at which the diagnosis was coded. Our objective was to estimate relative survival in epithelial ovarian cancer over the course of 10 years. METHODS: Using the Surveillance, Epidemiology and End Results 1995-2007 database, epithelial ovarian cancer cases were identified. Using the actuarial life table method, relative survival over the course of 10 years was calculated, stratified by stage, classification of residence, surgery as the first course of treatment, race, and age. RESULTS: There were 40,692 patients who met inclusion criteria. The overall relative survival was 65%, 44%, and 36% at 2, 5, and 10 years, respectively. The slope of decline in relative survival was reduced for years 5-10 as compared with years 1-5 after diagnosis. Relative survival at 5 years was 89%, 70%, 36%, and 17%, and at 10 years relative survival was 84%, 59%, 23%, and 8% for stages I, II III, and IV, respectively. At all stages, patients with nonsurgical primary treatment and those with advanced age had reduced relative survival. CONCLUSIONS: The 10-year relative survival for stage III is higher than expected. This information provides the physician and the patient with more accurate prognostic information.

As the number of total joint arthroplasty and internal fixation procedures continues to rise, the threat of infection following surgery has significant clinical implications. These infections may have highly morbid consequences to patients, who often endure additional surgeries and lengthy exposures to systemic antibiotics, neither of which are guaranteed to resolve the infection. Of particular concern is the threat of bacterial biofilm development, since biofilm-mediated infections are difficult to diagnose and effective treatments are lacking. Developing therapeutic strategies have targeted mechanisms of biofilm formation and the means by which these bacteria communicate with each other to take on specialized roles such as persister cells within the biofilm. In addition, prevention of infection through novel coatings for prostheses and the local delivery of high concentrations of antibiotics by absorbable carriers has shown promise in laboratory and animal studies. Biofilm development, especially in an arthoplasty environment, and future diagnostic and treatment options are discussed.

PURPOSE: Systemic exposure to mercaptopurine (MP) is critical for durable remissions in children with acute lymphoblastic leukemia (ALL). Nonadherence to oral MP could increase relapse risk and also contribute to inferior outcome in Hispanics. This study identified determinants of adherence and described impact of adherence on relapse, both overall and by ethnicity. PATIENTS AND METHODS: A total of 327 children with ALL (169 Hispanic; 158 non-Hispanic white) participated. Medication event-monitoring system caps recorded date and time of MP bottle openings. Adherence rate, calculated monthly, was defined as ratio of days of MP bottle opening to days when MP was prescribed. RESULTS: After 53,394 person-days of monitoring, adherence declined from 94.7% (month 1) to 90.2% (month 6; P < .001). Mean adherence over 6 months was significantly lower among Hispanics (88.4% v 94.8%; P < .001), patients age ≥ 12 years (85.8% v 93.1%; P < .001), and patients from single-mother households (80.6% v 93.1%; P = .001). A progressive increase in relapse was observed with decreasing adherence (reference: adherence ≥ 95%; 94.9% to 90%: hazard ratio [HR], 4.1; 95% CI,1.2 to 13.5; P = .02; 89.9% to 85%: HR, 4.0; 95% CI, 1.0 to 15.5; P = .04; < 85%: HR. 5.7; 95% CI, 1.9 to 16.8; P = .002). Cumulative incidence of relapse (± standard deviation) was higher among Hispanics (16.5% ± 4.0% v 6.3% ± 2.2%; P = .02). Association between Hispanic ethnicity and relapse (HR, 2.6; 95% CI, 1.1 to 6.1; P = .02) became nonsignificant (HR, 1.8; 95% CI, 0.6 to 5.2; P = .26) after adjusting for adherence and socioeconomic status. At adherence rates ≥ 90%, Hispanics continued to demonstrate higher relapse, whereas at rates < 90%, relapse risk was comparable to that of non-Hispanic whites. CONCLUSION: Lower adherence to oral MP increases relapse risk. Ethnic difference in relapse risk differs by level of adherence-an observation currently under investigation.

In Brief Objective: To evaluate the comparative effectiveness of sleeve gastrectomy (SG), laparoscopic gastric bypass (RYGB), and laparoscopic adjustable gastric banding (LAGB) procedures. Background: Citing limitations of published studies, payers have been reluctant to provide routine coverage for SG for the treatment of morbid obesity. Methods: Using data from an externally audited, statewide clinical registry, we matched 2949 SG patients with equal numbers of RYGB and LAGB patients on 23 baseline characteristics. Outcomes assessed included complications occurring within 30 days, and weight loss, quality of life, and comorbidity remission at 1, 2, and 3 years after bariatric surgery. Results: Matching resulted in cohorts of SG, RYGB, and LAGB patients that were well balanced on baseline characteristics. Overall complication rates among patients undergoing SG (6.3%) were significantly lower than for RYGB (10.0%, P < 0.0001) but higher than for LAGB (2.4%, P < 0.0001). Serious complication rates were similar for SG (2.4%) and RYGB (2.5%, P = 0.736) but higher than for LAGB (1.0%, P < 0.0001). Excess body weight loss at 1 year was 13% lower for SG (60%) than for RYGB (69%, P < 0.0001), but was 77% higher for SG than for LAGB (34%, P < 0.0001). SG was similarly closer to RYGB than LAGB with regard to remission of obesity-related comorbidities. Conclusions: With better weight loss than LAGB and lower complication rates than RYGB, SG is a reasonable choice for the treatment of morbid obesity and should be covered by both public and private payers. Citing limitations of published studies, payers have been reluctant to provide routine coverage for sleeve gastrectomy for the treatment of morbid obesity. Using data from a statewide, externally audited clinical registry, our study compares rates of complications, and weight loss, comorbidity remission, quality of life, and satisfaction for 3 years after bariatric surgery among nearly 9000 morbidly obese patients. We find that with better weight loss than adjustable gastric band and lower complication rates than gastric bypass, sleeve gastrectomy is a reasonable choice for the treatment of morbid obesity and should be covered by both public and private payers.

OBJECTIVE: To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]). RESEARCH DESIGN AND METHODS: Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days. RESULTS: Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ≥26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P < 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P < 0.001) and adults (7.7% vs. 7.9%, P < 0.001). In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year. CONCLUSIONS: CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.

BACKGROUND AND OBJECTIVE: Colonic dysbiosis contributes to the development of colonic inflammation in ulcerative colitis (UC). Fecal microbial transplantation (FMT) is being proposed as a novel treatment for UC because it can eliminate dysbiosis; however, no prospective data exist. We initiated a pilot study to evaluate feasibility and safety of FMT in children with UC. METHODS: Ten children, 7 to 21 years of age, with mild-to-moderate UC (pediatric UC activity index [PUCAI] between 15 and 65) received freshly prepared fecal enemas daily for 5 days. Data on tolerability, adverse events, and disease activity were collected during FMT and weekly for 4 weeks after FMT. Clinical response was defined as decrease in PUCAI by >15, and decrease in PUCAI to <10 was considered clinical remission. RESULTS: No serious adverse events were noted. Mild (cramping, fullness, flatulence, bloating, diarrhea, and blood in stool) to moderate (fever) adverse events were self-limiting. One subject could not retain fecal enemas. Average tolerated enema volume by remaining 9 subjects was 165 mL/day. After FMT, 7 of the 9 (78%) subjects showed clinical response within 1 week, 6 of the 9 (67%) subjects maintained clinical response at 1 month, and 3 of the 9 (33%) subjects achieved clinical remission at 1 week after FMT. Median PUCAI significantly improved after FMT (P = 0.03) compared with the baseline. CONCLUSIONS: Fecal enemas were feasible and tolerated by children with UC. Adverse events were acceptable, self-limiting, and manageable by subjects. FMT indicated efficacy in the treatment of UC.

BACKGROUND: Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery. METHODS: In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. The two primary end points were a four-component composite of death through day 30, renal-replacement therapy through day 30, perioperative myocardial infarction through day 5, or use of a mechanical cardiac assist device through day 5; and a two-component composite of death through day 30 or use of a mechanical cardiac assist device through day 5. RESULTS: A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo and were included in the modified intention-to-treat population. The four-component primary end point occurred in 105 of 428 patients (24.5%) assigned to receive levosimendan and in 103 of 421 (24.5%) assigned to receive placebo (adjusted odds ratio, 1.00; 99% confidence interval [CI], 0.66 to 1.54; P=0.98). The two-component primary end point occurred in 56 patients (13.1%) assigned to receive levosimendan and in 48 (11.4%) assigned to receive placebo (adjusted odds ratio, 1.18; 96% CI, 0.76 to 1.82; P=0.45). The rate of adverse events did not differ significantly between the two groups. CONCLUSIONS: Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. (Funded by Tenax Therapeutics; LEVO-CTS ClinicalTrials.gov number, NCT02025621 .).