The Medicago SymCEP7 hormone increases nodule number via shoots without compromising lateral root number.

Legumes acquire soil nutrients through nitrogen-fixing root nodules and lateral roots. To balance the costs and benefits of nodulation, legumes negatively control root nodule number by autoregulatory and hormonal pathways. How legumes simultaneously coordinate root nodule and lateral root development to procure nutrients remains poorly understood. In Medicago (Medicago truncatula), a subset of mature C-TERMINALLY ENCODED PEPTIDE (CEP) hormones can systemically promote nodule number, but all CEP hormones tested to date negatively regulate lateral root number. Here we showed that Medicago CEP7 produces a mature peptide, SymCEP7, that promotes nodulation from the shoot without compromising lateral root number. Rhizobial inoculation induced CEP7 in the susceptible root nodulation zone in a Nod factor-dependent manner, and, in contrast to other CEP genes, its transcription level was elevated in the ethylene signaling mutant sickle. Using mass spectrometry, fluorescence microscopy and expression analysis, we demonstrated that SymCEP7 activity requires the COMPACT ROOT ARCHITECTURE 2 receptor and activates the shoot-to-root systemic effector, miR2111. Shoot-applied SymCEP7 rapidly promoted nodule number in the pM to nM range at concentrations up to five orders of magnitude lower than effects mediated by root-applied SymCEP7. Shoot-applied SymCEP7 also promoted nodule number in White Clover (Trifolium repens) and Lotus (Lotus japonicus), which suggests that this biological function may be evolutionarily conserved. We propose that SymCEP7 acts in the Medicago shoot to counter balance the autoregulation pathways induced rapidly by rhizobia to enable nodulation without compromising lateral root growth, thus promoting the acquisition of nutrients other than nitrogen to support their growth.

Evolving trends in immunosuppression use and cytomegalovirus infection risk over the past decade in kidney transplantation.

BACKGROUND: The goal was to determine trends in immunosuppression use and its impact on cytomegalovirus (CMV) outcomes over the past 10 years. METHODS: This was a single-center longitudinal cohort study of adult kidney recipients transplanted between Jan 2012 and June 2021. Baseline and follow-up data were gathered via chart abstraction and analyzed using univariate and multivariate analyses. RESULTS: Of 2392 kidney transplants conducted, 131 patients did not meet inclusion criteria. The mean age was 52 years, 41% were female, 57% were black, and 19% were CMV high-risk. The use of rabbit anti-thymocyte globulin (RATG) induction (odds ratio [OR] 1.6, 1.3-2.1), tacrolimus (FK) level >8 ng/mL (OR 1.1, 1.09-1.11), CMV D+/R- rates (OR 1.06, 1.02-1.10), white blood cell count <3000 (OR 1.22, 1.18-1.26) and valganciclovir prophylaxis (OR 1.7, 1.6-1.9) have significantly increased over the past 10 years.  Rejection rates (OR 0.86, 0.82-0.91) and BK viremia >2000 (OR 0.91, 0.91-0.98) have decreased. RATG induction (adjusted hazard ratio [aHR] 1.35, 1.2-1.5), FK >8 ng/mL (aHR 3.5, 3.2-3.9), Belatacept conversion (aHR 2.5, 2.1-3.1), and rejection (aHR 1.8, 1.6-2.0) were significant risk factors for developing CMV infection, while mycophenolate mofetil <1500 mg (aHR 0.52, 0.47-0.59), mammalian target of rapamycin inhibitor (mTORi) conversion (0.77, 0.56-0.89), cyclosporine-A conversion (aHR 0.68, 0.56-0.84) were associated with lower risk of CMV infection. CONCLUSION: Increasing use of potent immunosuppression coupled with higher CMV D+/R- F rates may be driving higher rates of CMV infection. Cyclosporine and mTORi conversion appears to be protective against CMV.  A more individualized immunosuppression regimen based on infection risk merits consideration.

Impact of CYP3A5 genotype on de-novo LCP tacrolimus dosing and monitoring in kidney transplantation.

OBJECTIVES: LCP tac has a recommended starting dose of 0.14 mg/kg/day in kidney transplant. The goal of this study was to assess the influence of CYP3A5 on perioperative LCP tac dosing and monitoring. METHODS: This was a prospective observational cohort study of adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele). RESULTS: In this study, 120 were screened, 90 were contacted and 52 provided consent; 50 had genotype results, and 22 patients expressed CYP3A5*1. African Americans (AA) comprised 37.5% of nonexpressors versus 81.8% of expressors (P = 0.001). Initial LCP tac dose was similar between CYP3A5 groups (0.145 vs. 0.137 mg/kg/day; P = 0.161), whereas steady state dose was higher in expressors (0.150 vs. 0.117 mg/kg/day; P = 0.026). CYP3A5*1 expressors had significantly more tac trough concentrations of less than 6 ng/ml and significantly fewer tac trough concentrations of more than 14 ng/ml. Providers were significantly more likely to under-adjust LCP tac by 10 and 20% in CYP3A5 expressors versus nonexpressors (P < 0.03). In sequential modeling, CYP3A5 genotype status explained the LCP tac dosing requirements significantly more than AA race. CONCLUSION: CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers.

Impact of obesity on the conversion of immediate-release tacrolimus to extended-release tacrolimus in kidney transplant recipients.

Outcomes analyzing conversion from IR-tacrolimus (IR) to LCP-tacrolimus (LCP) in obesity are limited. This was a retrospective longitudinal cohort study of patients converted from IR to LCP from June 2019 to October 2020. Primary outcomes were conversion ratios for weight-based dose at a steady-state therapeutic level and identification of appropriate dosing weight. Other outcomes included tacrolimus coefficient of variation (CV), time in therapeutic range (TITR), adverse events, infections, donor specific antibodies (DSAs), and acute rejection. A total of 292 patients were included; 156 and 136 patients with a BMI < 30 and BMI ≥ 30 kg/m2 , respectively. Baseline characteristics were similar, except for pancreas transplant, diabetes, and HLA mismatch. IR to LCP conversion ratio ranged from .73 to .79. Mean LCP dose was similar (.08 vs. .07 mg/kg/day for BMI < 30 and BMI ≥ 30 kg/m2 , respectively); there was a significant difference in IR and LCP mg/kg dosing at steady state with TBW (.11 mg/kg vs.09 mg/kg and .08 mg/kg vs. .06 mg/kg, respectively). The most appropriate dosing weight was adjusted body weight (AdjBW), consistent across IR and LCP steady-state doses, and might yield more accurate steady-state dosing requirements. In multivariable modeling, BMI was a significant predictor of steady state mg/kg dosing at therapeutic goal for total body weight (TBW), but not ideal body weight (IBW) or AdjBW.

Impact of converting adult kidney transplant recipients with high tacrolimus variability from twice daily immediate release tacrolimus to once daily LCP-Tacrolimus.

BACKGROUND: The influence of converting to once daily, extended-release LCP-Tacrolimus (Tac) for those with high tacrolimus variability in kidney transplant recipients (KTRs) is not well-studied. METHODS: Single-center, retrospective cohort study of adult KTRs converted from Tac immediate release to LCP-Tac 1-2 years post-transplant. Primary measures were Tac variability, using the coefficient of variation (CV) and time in therapeutic range (TTR), as well as clinical outcomes (rejection, infections, graft loss, death). RESULTS: A total of 193 KTRs included with a follow-up of 3.2 ± .7 years and 1.3 ± .3 years since LCP-Tac conversion. Mean age was 52 ± 13 years; 70% were African American, 39% were female, 16% living donor and 12% donor after cardiac death (DCD). In the overall cohort, tac CV was 29.5% before conversion, which increased to 33.4% after LCP-Tac (p = .008). In those with Tac CV >30% (n = 86), conversion to LCP-Tac reduced variability (40.6% vs. 35.5%; p = .019) and for those with Tac CV >30% and nonadherence or med errors (n = 16), LCP-Tac conversion substantially reduced Tac CV (43.4% vs. 29.9%; p = .026). TTR significantly improved for those with Tac CV >30% with (52.4% vs. 82.8%; p = .027) or without nonadherence or med errors (64.8% vs. 73.2%; p = .005). CMV, BK, and overall infections were significantly higher prior to LCP-Tac conversion. In the overall cohort, 3% had rejection before conversion and 2% after (p = NS). At end of follow-up, graft and patient survival were 94% and 96%, respectively. CONCLUSIONS: In those with high Tac CV, conversion to LCP-Tac is associated with a significant reduction in variability and improvement in TTR, particularly in those with nonadherence or medication errors.

Diabetes is a significant and independent predictor for tacrolimus immediate release and LCP-tacrolimus conversion ratios.

Diabetes (DM) is a common comorbidity in transplant patients with known effects on gastrointestinal (GI) motility and absorption; however, DM's impact on immediate release (IR) tacrolimus to LCP-tacrolimus (LCP) conversion ratios has not been studied. This multivariable analysis of a retrospective longitudinal cohort study included kidney transplant recipients converted from IR to LCP between 2019 and 2020. The primary outcome was IR to LCP conversion ratio based on DM status. Other outcomes included tacrolimus variability, rejection, graft loss, and death. Of the 292 patients included, 172 patients had DM and 120 did not. The IR:LCP conversion ratio was significantly higher with DM (67.5% ± 21.1% no DM vs. 79.8% ± 28.7% in DM; P < .001). In multivariable modeling, DM was the only variable significantly and independently associated with IR:LCP conversion ratios. No difference was observed in rejection rates. Graft (97.5% no DM vs. 92.4% in DM; P = .062) and patient survival (100% no DM vs. 94.8% in DM; P = .011) were lower with DM. The presence of DM significantly increased the IR:LCP conversion ratio by 13%-14%, compared to patients without DM. On multivariable analysis, DM was the only significant predictor of conversion ratios, potentially related to GI motility or absorption differences.

Movement disorders in hereditary spastic paraplegia (HSP): a systematic review and individual participant data meta-analysis.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a rare genetic disorder associated with mutations in > 80 loci designated SPG (SPastic parapleGia). The phenotypic spectrum of HSP can extend to include other neurologic features, including movement disorders. Our aim was to investigate genotype-phenotype associations in HSP with a focus on movement disorders. METHODS: We performed a systematic review and individual participant data (IPD)-level meta-analysis by retrieving publications from Medline/EMBASE/Web of Science on HSP with a SPG genotype. Studies were included only if individual-level information was accessible and at least one patient with a movement disorder was reported for that genotype. Out of 21,957 hits, 192 manuscripts with a total of 1413 HSP cases were eligible. Data were compared between two HSP groups: manifested with (HSP-MD, n = 767) or without (HSP-nMD, n = 646) a movement disorder. RESULTS: The HSP-MD group had an older age of onset (20.5 ± 16.0 vs. 17.1 ± 14.2 yr, p < 0.001) and less frequent autosomal dominant inheritance (7.6% vs. 30.1%, p < 0.001) compared to HSP-nMD. SPG7 (31.2%) and SPG11 (23.8%) were the most frequent genotypes in the HSP-MD group. HSP-MD with SPG7 had higher frequency of later onset during adulthood (82.9% vs. 8.5%), ataxia (OR = 12.6), extraocular movement disturbances (OR = 3.4) and seizure (OR = 3.7) compared to HSP-MD with SPG11. Conversely, SPG11 mutations were more frequently associated with consanguinity (OR = 4.1), parkinsonism (OR = 7.8), dystonia (OR = 5.4), peripheral neuropathy (OR = 26.9), and cognitive dysfunction (OR = 34.5). CONCLUSION: This systematic IPD-level meta-analysis provides the largest data on genotype-phenotype associations in HSP-MD. Several clinically relevant phenotypic differences were found between various genotypes, which can possibly facilitate diagnosis in resource-limited settings.

A Versatile Prison Psychiatric Pharmacy Program.

BACKGROUND: Before the coronavirus disease 2019 (COVID-19) pandemic, 20% of the adult population in the United States experienced mental illness annually. Since the COVID-19 pandemic, 93% of countries have reported disruptions to mental health services. The demand for services is high whereas infrastructure and qualified professionals are appallingly low. Health care in the correctional setting is unique, where mental illness prevalence is double than that in the community. The intersection of policies and procedures and the beneficence plus nonmaleficence responsibility of health care professionals is exceptionally complex. Studies have shown the potential benefits of pharmacists following patients in chronic care psychiatry visits. OBJECTIVES: An inpatient psychiatric pharmacy clinic was launched to fill gaps to provide safe and up-to-date patient-centric services for more than 240 extremely psychiatrically ill inmate patients at the Federal Correctional Center Butner (FCC Butner), a Federal Bureau of Prisons medical center. METHODS: The inpatient psychiatric pharmacist practiced independently under a collaborative practice agreement and completed mental health clinical visits for a revolving portion of 240 inpatient mental health inmate patients at FCC Butner. The pharmacist provided ancillary services including completing movement disorder testing, monitoring narrow therapeutic index medication laboratory test results, and executing an antipsychotic psychoeducation meeting with other health care departments and inmate patients. RESULTS: Notably, 74% of patients monitored in the specialty program experienced stable or improved symptoms of depression, schizophrenia, and bipolar disorder. Adverse effects, particularly psychiatric-related movement disorders, were also more closely managed. Finally, 43% of the total inmate patient population who previously declined psychiatric medication treatment consented to begin treatment after participation in a pilot antipsychotic psychoeducation meeting. CONCLUSION: The inpatient psychiatric pharmacy program at FCC Butner is a dynamic program that has bolstered the facility's health care mission. The services detailed in this article can be applied to other correctional environments that have a medical outpatient or inpatient presence.

A centennial review of discoveries and advances in diabetes: Children and youth.

Diabetes is an increasingly common chronic metabolic disorder in children worldwide. The discovery of insulin in 1921 resulted in unprecedented advancements that improved the lives of children and youth with diabetes. The purpose of this article is to review the history of diabetes in children and youth over the last century and its implications for future developments in the field. We identified 68 relevant events between 1921 and 2021 through literature review and survey of pediatric endocrinologists. Basic research milestones led to the discovery of insulin and other regulatory hormones, established the normal physiology of carbohydrate metabolism and pathophysiology of diabetes, and provided insight into strategies for diabetes prevention. While landmark clinical studies were initially focused on adult diabetes populations, later studies assessed etiologic factors in birth cohort studies, evaluated technology use among children with diabetes, and investigated pharmacologic management of youth type 2 diabetes. Technological innovations culminated in the introduction of continuous glucose monitoring that enabled semi-automated insulin delivery systems. Finally, professional organizations collaborated with patient groups to advocate for the needs of children with diabetes and their families. Together, these advances transformed type 1 diabetes from a terminal illness to a manageable disease with near-normal life expectancy and increased our knowledge of type 2 diabetes and other forms of diabetes in the pediatric population. However, disparities in access to insulin, diabetes technology, education, and care support remain and disproportionately impact minority youth and communities with less resources. The overarching goal of diabetes management remains promoting a high quality of life and improving glycemic management without undermining the psychological health of children and youth living with diabetes.

Contemporary trends and in-hospital outcomes of catheter and stand-alone surgical ablation of atrial fibrillation.

AIMS: The contemporary trends in catheter ablation (CA) and surgical ablation (SA) utilization and surgical techniques [open vs. thoracoscopic, with or without left atrial appendage closure (LAAC)] are unclear. In addition, the in-hospital outcomes of stand-alone SA compared with CA are not well-described. METHODS AND RESULTS: The National Inpatient Sample 2010-18 was queried for atrial fibrillation (AF) hospitalizations with CA or stand-alone SA. Complex samples multivariable logistic and linear regression models were used to compare the association between stand-alone SA vs. CA and the primary outcomes of in-hospital mortality and stroke. Of 180 243 hospitalizations included within the study, 167 242 were for CA and 13 000 were for stand-alone SA. Catheter ablation and stand-alone SA hospitalizations decreased throughout the study period (Ptrend < 0.001). Surgical ablation had higher rates of in-hospital mortality [adjusted odds ratio (aOR) 2.26; 95% confidence interval (CI) 1.41-3.61; P = 0.001] and stroke (aOR 4.64; 95% CI 3.25-6.64; P < 0.001) compared with CA. When examining different surgical approaches, thoracoscopic SA was associated with similar in-hospital mortality (aOR 1.53; 95% CI 0.60-3.89; P = 0.369) and similar risk of stroke (aOR 1.75; 95% CI 1.00-3.07; P = 0.051) compared with CA. CONCLUSION: Stand-alone SA comprises a minority of AF ablation procedures and is associated with increased risk of mortality, stroke, and other in-hospital complications compared to CA. However, when a thoracoscopic approach was utilized, the risks of mortality and stroke appear to be reduced.

Fluvoxamine in Nonhospitalized Patients With Acute COVID-19 Infection and the Lack of Efficacy in Reducing Rates of Hospitalization, Mechanical Ventilation, and Mortality in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent clinical trials have investigated the use of fluvoxamine in preventing clinical deterioration in nonhospitalized patients with acute COVID-19 infection via stimulation of sigma-1 receptors, which regulates cytokine production and functional inhibition of acid sphingomyelinase activity, which may prevent infection of epithelial cells with SARS-CoV-2. However, the role of fluvoxamine is currently unclear because of a paucity of studies, particularly because the drug is being repurposed as an immunomodulatory and antiviral agent. STUDY QUESTION: Aim of our meta-analysis was to investigate the efficacy of fluvoxamine in nonhospitalized patients with acute COVID-19 infection. DATA SOURCE: Comprehensive literature search of PubMed, Embase, Cochrane Library databases, and Web of Science was performed from inception to February 10, 2022, for studies comparing fluvoxamine versus placebo for outpatient management of COVID-19. STUDY DESIGN: The primary outcome of interest was rate of hospitalization. The secondary outcomes were rates of patients requiring mechanical ventilation and mortality. The random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). A P value <0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. RESULTS: Three studies (2 randomized controlled trials and one prospective cohort trial) involving 1762 patients were included in the meta-analysis. In patients who received fluvoxamine compared with placebo, there was no significant difference in rates of hospitalization (RR 0.26, 95% CI, 0.04-1.73, P = 0.16, I2 = 62%), mechanical ventilation (RR 0.73, 95% CI, 0.45-1.19, P = 0.21, I2 = 0%), and mortality (RR 0.67, 95% CI, 0.37-1.22, P = 0.19, I2 = 0%). CONCLUSION: Current evidence does not indicate a significant effect of fluvoxamine on the rates of hospitalization, mechanical ventilation, and mortality of patients with COVID-19 infection.

Ventricular fibrillation arrest after blunt chest trauma in a 33-year-old man, commotio cordis?

BACKGROUND: Commotio cordis is an event in which a blunt, non-penetrating blow to the chest occurs, triggering a life-threatening arrhythmia and often sudden death. This phenomenon is often seen in young, male athletes and has become increasingly well-known over the past few decades. We present a unique case in which ventricular fibrillation occurs in an older male athlete after blunt trauma. CASE PRESENTATION: Patient with no known medical history was brought to the ER after being found unconscious after a soccer ball kick to the chest. He was found to be in ventricular fibrillation and successfully resuscitated on the soccer field. Patient was admitted to the hospital and lab workup and initial imaging were unremarkable, except elevated troponin and lactate, which returned to normal levels. An echocardiogram showed global left ventricular systolic dysfunction with a visually estimated ejection fraction of 45-50%. Coronary showed angiographically nonobstructive coronary arteries. The patient was diagnosed with commotio cordis and discharged from the hospital in stable condition. Follow-up echocardiogram continued to show low ejection fraction and event monitor demonstrated frequent polymorphic ventricular tachycardia with periods of asystole. CONCLUSION: This case is unique in that blunt trauma to the chest from a soccer ball immediately triggered ventricular fibrillation in a patient with a possible cardiomyopathy. It is possible that the blunt trauma caused primary commotio cordis that led to cardiomyopathy in a previous healthy man, or that an underlying cardiomyopathy made it more likely for this to occur. Overall, increased awareness and prevention efforts of blunt chest trauma are required to reduce the high mortality associated life-threatening arrhythmias. There is limited data regarding the interplay between these two entities.

Early Adopters of Apple Health Records at a Large Academic Medical Center: Cross-sectional Survey of Users.

BACKGROUND: Mobile applications offer a new approach to personal health records, which are internet-based tools for patients to consolidate and manage their health information. The University of Pennsylvania Health System (UPHS) was one of the first health systems to participate in Apple Health Records (AHR), a prominent example of this new generation of personal health records. OBJECTIVE: This study aimed to characterize early adoption of AHR among UPHS patients and understand user perspectives. METHODS: An email-based survey with fixed answer, Likert scale, and open-ended questions was administered to all UPHS patients using AHR in the first 10 months of enrollment. Survey data linked to the UPHS electronic health record system were used to analyze responses. Multivariable logistic regression modeled the association of patient characteristics with user ratings. Content analysis was used to analyze open-ended questions. RESULTS: At the time of the survey, a total of 1458 patients had used AHR at least once. Mean age of AHR users was 47.5 years, 66.3% (967/1458) were male, 70.9% (1033/1458) were white, and 80.8% (1178/1458) had private insurance. Response rate was 26.8% (391/1458); 46.3% (180/389) were very satisfied with AHR, and 67.7% (264/390) described it as very easy to use. The most commonly utilized features were lab results (324/391, 82.9%), clinical vitals (264/391, 67.5%), and medications (253/391, 64.7%). No patient characteristics were associated with reporting high satisfaction or ease of use. The most common reason for using AHR was convenience/ease of use, and 58.2% (160/275) of users reported allowing no other apps to access their health information, citing privacy as one consideration. CONCLUSIONS: Early adopters of AHR were demographically white, male, and privately insured. Convenience was an important facilitator, and users were selective in which apps they allowed to access their health information.

Dynamics of lidocaine in topical anesthesia for office-based laryngeal procedures: A pilot study.

OBJECTIVES: To study topical lidocaine for office-based laryngeal procedures recording onset, duration, and subjective experience of topical anesthesia. STUDY DESIGN: Nine healthy volunteers were anesthetized with 4 % lidocaine endoscopically. Laryngeal sensitivity prior to and during anesthesia was recorded until normal sensation returned measured by air-puff sensory testing. Subjective experience of the process was recorded. METHODS: Questionnaires regarding subjective experience were completed prior to, during, and after anesthesia. Laryngeal sensitivity via air-pulse trigger of the laryngeal adductor reflex (LAR) prior to and after 3 mL shower of 4 % lidocaine was recorded at 30 second intervals until the larynx was insensate with no LAR at 10 mmHg. Time to anesthesia was recorded and post-endoscopy questionnaire was given. Upon subjective change in sensation, sensitivity via air-pulse trigger of the LAR was recorded until baseline sensation returned. A post-anesthesia questionnaire recorded the subjective experience. RESULTS: Average time to full anesthesia was 110 s (±31.2). Subjective return of sensation was noted at 10 min (±2.5), however time to return to normal LAR was 22 min (±5.8). Based on three standard deviations, 99.7 % of the population will be anesthetized at 3.4 min, report subjective change at 18.2 min and regain full sensation at 40 min. CONCLUSIONS: Office-based laryngeal procedures should be performed at least 2 min following topical 4 % lidocaine with a window for manipulation of at least 16 min. Oral intake should be delayed for over 45 min to ensure complete return of sensation. The laryngeal shower of lidocaine is subjectively tolerated. LEVEL OF EVIDENCE: 2C Outcomes Research.

Multi-institutional quality improvement case series: Pediatric airway emergencies leading to the creation of a pediatric otolaryngology airway cart.

To describe a specialty pediatric airway emergency cart developed as a multi-institutional quality improvement initiative for difficult pediatric intubations. This study was a retrospective case series at two academic tertiary care centers. Baseline data was compiled from consecutive difficult airway cases from 2018 to 2020 and presented to the performance improvement coordinating group to determine whether a specialty emergency airway cart would be of use. Implementation of a pediatric emergency airway cart was accomplished after presentation of these cases. To our knowledge, this is the first description of the use of a specialty pediatric airway cart to help in difficult airways requiring otolaryngologic assistance.

Access to a Labile Monomeric Magnesium Radical by Ball-Milling.

In order to isolate a monometallic Mg radical, the precursor (Am)MgI⋅(CAAC) (1) was prepared (Am=tBuC(N-DIPP)2 , DIPP=2,6-diisopropylphenyl, CAAC=cyclic (alkyl)(amino)carbene). Reduction of a solution of 1 in toluene with the reducing agent K/KI led to formation of a deep purple complex that rapidly decomposed. Ball-milling of 1 with K/KI gave the low-valent MgI complex (Am)Mg⋅(CAAC) (2) which after rapid extraction with pentane and crystallization was isolated in 15 % yield. Although a benzene solution of 2 decomposes rapidly to give Mg(Am)2 (3) and unidentified products, the radical is stable in the solid state. Its crystal structure shows planar trigonal coordination at Mg. The extremely short Mg-C distance of 2.056(2) Šindicates strong Mg-CAAC bonding. Calculations and EPR measurements show that most of the spin density is in a π* orbital located at the C-N bond in CAAC, leading to significant C-N bond elongation. This is supported by calculated NPA charges in 2: Mg +1.73, CAAC -0.82. Similar metal-to-CAAC charge transfer was calculated for M0 (CAAC)2 and [MI (CAAC)2 + ] (M=Be, Mg, Ca) complexes in which the metal charges range from +1.50 to +1.70. Although the spin density of the radical is mainly located at the CAAC ligand, complex 2 reacts as a low-valent MgI complex: reaction with a I2 solution in toluene gave (Am)MgI⋅(CAAC) (1) as the major product.

Estimated Incidence of Coronavirus Disease 2019 (COVID-19) Illness and Hospitalization-United States, February-September 2020.

BACKGROUND: In the United States, laboratory-confirmed coronavirus disease 2019 (COVID-19) is nationally notifiable. However, reported case counts are recognized to be less than the true number of cases because detection and reporting are incomplete and can vary by disease severity, geography, and over time. METHODS: To estimate the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, symptomatic illnesses, and hospitalizations, we adapted a simple probabilistic multiplier model. Laboratory-confirmed case counts that were reported nationally were adjusted for sources of underdetection based on testing practices in inpatient and outpatient settings and assay sensitivity. RESULTS: We estimated that through the end of September, 1 of every 2.5 (95% uncertainty interval [UI]: 2.0-3.1) hospitalized infections and 1 of every 7.1 (95% UI: 5.8-9.0) nonhospitalized illnesses may have been nationally reported. Applying these multipliers to reported SARS-CoV-2 cases along with data on the prevalence of asymptomatic infection from published systematic reviews, we estimate that 2.4 million hospitalizations, 44.8 million symptomatic illnesses, and 52.9 million total infections may have occurred in the US population from 27 February-30 September 2020. CONCLUSIONS: These preliminary estimates help demonstrate the societal and healthcare burdens of the COVID-19 pandemic and can help inform resource allocation and mitigation planning.

Global Seasonal Influenza Mortality Estimates: A Comparison of 3 Different Approaches.

Prior to updating global influenza-associated mortality estimates, the World Health Organization convened a consultation in July 2017 to understand differences in methodology and implications for results of 3 influenza mortality projects from the US Centers for Disease Control and Prevention (CDC), the Netherlands Institute for Health Service Research's Global Pandemic Mortality Project II (GLaMOR), and the Institute for Health Metrics and Evaluation (IHME). The expert panel reviewed estimates and discussed differences in data sources, analysis, and modeling assumptions. We performed a comparison analysis of the estimates. Influenza-associated respiratory death counts were comparable between CDC and GLaMOR; the IHME estimate was considerably lower. The greatest country-specific influenza-associated fold differences in mortality rate between CDC and IHME estimates and between GLaMOR and IHME estimates were among countries in Southeast Asia and the Eastern Mediterranean region. The data envelope used for the calculation was one of the major differences (CDC and GLaMOR: all respiratory deaths; IHME: lower-respiratory infection deaths). With the assumption that there is only one cause of death for each death, IHME estimates a fraction of the full influenza-associated respiratory mortality that is measured by the other 2 groups. Wide variability of parameters was observed. Continued coordination between groups could assist with better understanding of methodological differences and new approaches to estimating influenza deaths globally.

Signet Ring Cell Gastric Carcinoma: Clinical Epidemiology and Outcomes in a Predominantly Latino County Hospital Population.

BACKGROUND: Gastric signet ring cell carcinoma (GSRC) is a rare but increasingly prevalent tumor histotype whose clinical features and natural history are poorly understood, particularly in the USA and minorities. AIMS: To examine the occurrence, clinico-demographic characteristics, oncologic features, treatment, and outcomes of GSRC in a predominantly minority county hospital setting and benchmark them against data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. METHODS: We queried biopsy-proven GSRC cases at a Los Angeles County hospital, from 2004 to 2017. Clinical characteristics, treatment, and survival data were collected and compared to SEER data. RESULTS: We identified 63 patients with GSRC. Compared to SEER, our cohort was significantly younger (52.6 vs. 63.5 years, p < 0.01), Hispanic/Latino predominant (81% vs. 20%, p < 0.01), had higher overall stage (86% vs. 69% with stage III/IV, p < 0.01), and more frequent node involvement (89% vs. 49%, p < 0.01). Lower tumor stage, Helicobacter pylori positivity, and surgical intervention were associated with significantly longer median survival (all p < 0.05), which was similar in our study compared to SEER (median 12.6 vs. 9.0 months, p = 0.26). CONCLUSIONS: Patients with GSRC within the Los Angeles County population have different clinical characteristics compared to what has been reported in SEER. Our cohort was younger, and despite having more advanced disease, did not have shorter survival. Further study is needed to better identify protective and risk factors in this population and improve understanding of the etiopathogenesis and natural history of this malignancy.

Adenoidectomy: Inpatient criteria study.

OBJECTIVES: Current practices for admission for overnight observation after an adenoidectomy alone vary from hospital to hospital, as there are currently no studies that provide evidence for overnight observation criteria. The objective of this study is to determine any relationships between risk factors and postoperative complications or interventions in patients under 2-years-old who undergo adenoidectomy and use this data to form a set of guidelines that may be used to stratify patients for inpatient observation. METHODS: Consecutive pediatric adenoidectomy without tonsillectomy cases in children younger than 2-years-old with subsequent inpatient observation from January 2014 to October 2018 were reviewed at a single tertiary children's institution using electronic medical records. Patient demographics, surgical data, and comorbidities were analyzed for correlations with postoperative complications or interventions. RESULTS: Out of the 76 patients with sleep-disordered breathing (SDB) examined, one patient (1.3%) required readmission for postoperative dehydration and seven patients (9.2%) required intervention. The presence of at least one major comorbidity was significantly associated with increased incidence of complication or intervention compared to patients with no major comorbidities (18.9% vs. 2.6%, p = 0.03). Specifically, O2 nadir <80% (p = 0.01), craniofacial syndrome (p = 0.01) and seizure history (p = 0.007) were significant factors of complication or intervention. CONCLUSIONS: Otherwise healthy children (>18-month-old) with SDB may be considered for discharge the same day of surgery. Children younger than 2-years-old with ≥1 major comorbidities may benefit from overnight inpatient observation. Otherwise healthy children younger than 18-months-old or children with a history of RAD or CLD should be managed on a case-by-case basis.