Additional Therapeutic Interventions Research Articles

Drug development targeting SARS-CoV-2 main protease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are responsible for the devastating coronavirus disease 2019 (COVID-19) pandemic with more than 6.5 million deaths since 2019. Although a number of vaccines significantly reduced the mortality rate, a large number of the world population is yet being infected with highly contagious omicron variants/subvarints. Additional therapeutic interventions are needed to reduce hospitalization and curb the ongoing pandemic. The activity of the SARS-CoV-2 enzyme; chymotrypsin-like main protease (Mpro) is essential for the cleavage of viral nonstructural polypeptides into individual functional proteins and therefore Mpro is an attractive drug target. The aim of this review is to summarize recent progress toward the development of therapeutic drugs against Mpro protease.

Achieving MRD negativity in AML: how important is this and how do we get there?

Multiple studies have demonstrated that patients with acute myeloid leukemia (AML) who have measurable residual disease (MRD) detected during or after treatment have higher relapse rates and worse survival than similar patients testing negative. Updated response criteria for AML reflect the understanding that achievement of complete remission (CR) with no detectable MRD using high-sensitivity tests represents a superior response over conventional cytomorphological CR alone. Potential use cases for AML MRD testing are diverse and include patient selection for clinical trials and therapeutic assignment, early relapse detection and intervention during sequential monitoring, and drug development, including deep quantification for antileukemia efficacy and as a surrogate endpoint for overall survival in regulatory approvals. Testing for AML MRD has not, however, been harmonized, and many technical and clinical questions remain. The implications of MRD test results for specific therapeutic combinations, molecular subsets, test types, treatment time points, sample types, and patient characteristics remain incompletely defined. No perfect AML MRD test or testing strategy currently exists, and the evidence basis for clinical recommendations in this rare disease is sparse but growing. It is unproven whether conversion of an MRD test result from positive to negative by additional therapeutic intervention improves relapse risk and survival. Several national- and international-level consortia have recently been initiated to advance the generation and collection of evidence to support the use of AML MRD testing in clinical practice, drug development, and regulatory approvals.

BENIGN ENLARGEMENT OF SUBARACHNOID SPACES IN INFANTS

Benign enlargement of subarachnoid spaces (BESS) constitutes is one of the most frequent neurosonographic findings in infancy and is considered to regress spontaneously by the age of 2 years. Although the majority of children with BESS demonstrate normal developmental milestones, some patients may experience a transient psychomotor delay under the age of 2 year. Besides clinical andneuroimaging findings, the long-term impact of BESS is of great interest (learning difficulties at school, language delay, impairmentsin social-cognitive abilities, reduced quality of life, decreased attention skills and poor visual-motor performance, increased risk ofautism spectrum disorders as well as a higher incidence of epilepsy). It is considered that the risk of long-term consequences may be associated with pathogenetic features of dilation of extra-axial cerebrospinal fluid spaces. In this review, we describe potentialpathogenetic mechanisms of dilatation of the subarachnoid space and its pathological sequelae in children. Generally, numerous pathogenetic hypotheses about developing BESS have been proposed as follows: remarkable physiological imbalance between the skull and brain growth in infants aged from three months to one year; manifestation of cerebral trophy; communicating hydrocephalus due to a distal block with a valve mechanism; a delay in maturation of arachnoid villi/granulations until two years of age; the result of abusive head trauma in infants. However, the hypothesis about pathological consequences of BESS in the long run due to abnormalvenous hemodynamics has emerged in recent years. Impaired venous outflow is the main driving factor of subarachnomegaly and the more severe pathological changes the more significant symptoms of subarachnomegaly. We also highlight the role of impaired cerebralvenous circulation in the development of subarachnomegaly. Further studies are needed to investigate the clinical relevance of chronic increased intracranial pressure due to venous outflow disturbance in infants with enlarged subarachnoid spaces.Тhe subject for future research should be to determine a diagnostic algorithm to help distinguish patients with BESS from those who are at risk of impairedneurological development and require additional diagnostic and therapeutic interventions.

Day of surgery cancellation in total shoulder arthroplasty: an analysis of surgical cancellation etiologies

BackgroundCancellation of elective total shoulder arthroplasty (TSA) is an expected occurrence. The typical cost of canceled elective surgeries is estimated to be $3000 per patient and can lead to hospital losses of nearly $1 million per year. With the growing interest of same-day TSA, understanding and minimizing unexpected same-day cancellation will reduce impact on patients, surgeons, and health care system. The purpose of the study is to identify the frequency and causes of unexpected same-day cancellations in TSA and determine which treatment path those patients take following their cancellation. MethodsA consecutive series of 1189 TSA (anatomic and reverse) patients operated at a single-academic institution across two tertiary care hospitals from 2010 to 2020 were reviewed. All patients who were scheduled for TSA and subsequently canceled were identified. The etiology of cancellation, time to rescheduling, date of actual TSA procedure, and subsequent work-up were recorded. Descriptive statistics of the canceled patient cohorts were analyzed. Univariate analysis, chi-square test, and analysis of variance were used to compare patients who canceled on the day of surgery (DOS) to prior to surgery. ResultsOf the 1189 TSA patients, 964 were TSA for primary glenohumeral osteoarthritis or cuff tear arthropathy. Ninety-eight (10.2%) TSA had cancellations, of which 49.0% were on the DOS. Most common causes of DOS cancellations were due to medical reasons (45.8%) and anesthesia-related complications (27.1%). Infection (40.9%) was the most frequent medical reasons for cancellations. Fifty-four percent of the anesthesia-related complication cancellations underwent additional diagnostic and therapeutic intervention, despite 100 % of those patients receiving preoperative clearance. DiscussionDOS cancellations in TSA are unavoidable, but there are modifiable factors that can minimize the risk of cancellation. Contrary to studies that attributed cancellations to inadequate cardiovascular-related medical clearance, our study found that the majority of these cancellations are due to infection-related issues. A higher proportion of patients with inadequate medical clearance will cancel prior to the DOS. Despite preoperative optimization, certain patient risk factors need additional diagnostic and therapeutic interventions prior to undergoing shoulder arthroplasty. Through coordination and planning, health care providers and patients can identify those factors and address these issues early on to avoid cancellation and ultimately proceed with a TSA.

A Recurring Burden: Examining Readmission and Related Cost in the Months after Pancreaticoduodenectomy

Introduction: Readmission after pancreaticoduodenectomy (PD) is common and serves to escalate cost of an already challenging and expensive procedure. Existing literature on discrete cost after PD admission is limited. Methods: A prospectively maintained PD cost database, which includes cost [divided into operating room, postoperative/ward, radiology, interventional radiology (IR)] for index hospitalization and episodes-of-care within 90 days of surgery, was queried for readmission. Baseline characteristics, reasons for readmission, and intervention were studied, and index and 90-day cost compared within the same group. Results: A total of 1284 patients underwent PD from 2010-2019. 90-day cost were available for 460 patients, of which 88 readmitted patients with complete data were analyzed. Patients were readmitted 1.3±0.7 times on average. Mean readmission length of stay (LoS) was 9.7±9.1 days, which was not significantly shorter (p = 0.549) than index LoS (10.4±7.8 days). Median total 90-day cost was $15,780 ($1,237-102,913), which was significantly lower (p < 0.001) than cost of index hospitalization [$27,212 ($15,573-155,042)]. Common reasons for readmission were food intolerance and/or failure to thrive (n = 17, 19.3%), abdominal fluid collection (n = 13, 14.8%), and postsurgical abdominal pain (n = 13, 14.8%). Patients were treated by surgery (eg exploratory laparotomy, PEG tube placement) (n = 13, 14.8%) or IR (eg CT guided drain placement) (n = 33, 37.5%) while the rest (n = 45, 51.1%) were managed medically. 90-day mortality in this cohort was 2.2% (n = 2). Conclusion: Although patients readmitted after PD incur lower 90-day cost than their index stay, LoS is comparable, and many undergo additional therapeutic intervention. This underscores the complexity of PD, which affects recovery and finances well beyond the operation itself.

S1119 Safety and Efficacy of Pediatric Endosonography: A Multi-Center Retrospective Cohort Study

Introduction: Endoscopic ultrasound (EUS) is widely used in the adult population for a wide range of diagnostic and therapeutic purposes. In the pediatric population, the use of EUS has been historically diagnostic, however, EUS-guided therapy is increasing. In this retrospective study, we aim to describe the safety and efficacy profiles of EUS in pediatric patients across a spectrum of EUS procedures. Methods: This is a retrospective multi-center cohort study of pediatric patients who underwent EUS procedures for diagnostic or therapeutic purposes between January 2011 and March 2022. Data including demographics, procedural details, and adverse events (AE) were collected. Outcomes were diagnostic success, defined as successful diagnosis using only EUS without any additional diagnostic tools, and therapeutic success, defined as using only EUS without additional therapeutic interventions. Results: 61 pediatric patients between the age of 0 to 18 years underwent 77 EUS procedures, of which 35 were females (56.5%). The mean age at the procedure was 16.2 ± 4.2 years and the median weight was 70.2 kg (IQR 49.7-91.2). The indications for EUS were gastrointestinal lumen evaluation ± fine needle biopsy/aspiration (FNB/A), pancreaticobiliary tree evaluation ±FNB/A, surveillance for tumor syndrome, suspected lymph node (LN), or gastrointestinal (GI) mass, celiac plexus block and cyst gastrostomy creation (Table). The median procedure time was 35 minutes (IQR 18 – 49). The diagnostic success rate was 98.7% and the therapeutic success rate was 100%. The complication rate was 2.6% which included 2 cases of pancreatitis after fine-needle aspiration of the pancreas. No case had any anesthesia-related complications. Conclusion: In this multicenter retrospective cohort study, the use of EUS in pediatrics has shown to be safe and effective in a wide range of diagnostic and therapeutic intents. Table 1. - Baseline characteristics, procedural and clinical outcomes of pediatric patient EUS procedures N=77 (%) Females 35 (56.5) Weight (n=66) 70.2 [49.7 – 91.2] Age at procedure (years) 16.2 ± 4.2 Indication Diagnostic GI lumen Evaluation 9 (11.7) GI lumen Evaluation with FNB/A 5 (6.5) Pancreaticobiliary tree evaluation 37 (48.1) Pancreaticobiliary tree evaluation with FNB/A 6 (7.8) Surveillance for tumor syndrome 7 (9.1) Suspected LN or mass 8 (10.4) Therapeutic Celiac Plexus Block 1 (1.3) Cystgastrostomy 4 (5.2) Anesthesia Type Monitored Anesthesia Care (MAC) 48 (62.3) General Anesthesia 29 (37.7) Mean procedure Time in minutes (N= 59) 35.0 [18.0 - 49.0] Diagnostic Success 76 (98.7) Therapeutic Success (n=5) 5 (100) EUS related complications 2 (2.6) Anesthesia complications 0 (0) EUS = endoscopic ultrasound, FNA/B = fine needle aspiration/biopsy, LN = lymph node.Continuous variables presented as mean ± SD or median (IQR).Categorical variables presented as n (%).

Risk Factors Associated with Clinical Failure of Uterine Artery Embolization for Postpartum Hemorrhage

PurposeTo identify risk factors for clinical failure of uterine artery embolization (UAE) for postpartum hemorrhage (PPH), with particular attention to the uterine artery diameter. Materials and MethodsThis retrospective study included 47 patients who underwent UAE for PPH between January 1, 2010, and January 31, 2021. Technical success was defined as the completion of embolization of the arteries thought to be the cause of the bleeding. Clinical success was defined as no recurrent bleeding or need for additional therapeutic interventions. Univariate and multivariate analyses were performed to examine the risk factors associated with clinical failure of UAE. ResultsOf the 47 patients, 6 had recurrent bleeding. Of the 6 patients, 4 underwent hysterectomy, and 2 underwent repeat embolization. The clinical success rate was 87.2% (41/47), with no major adverse events such as uterine infarction or death. In univariate analysis, there were slight differences in multiparity (P = .115) and placental abruption (P = .128) and a significant difference in the findings of a narrow uterine artery on digital subtraction angiography (DSA) (P = .005). In multivariate analysis, only a narrow uterine artery on DSA was a significant factor (odds ratio, 18.5; 95% confidence interval, 2.5–134.8; P = .004). ConclusionsA narrow uterine artery on DSA was a risk factor for clinically unsuccessful UAE for PPH. It may be prudent to conclude the procedure only after it is ensured that vasospasm has been relieved.

Impact of epinephrine volume on further bleeding due to high-risk peptic ulcer disease in the combination therapy era.

BACKGROUNDIn monotherapy studies for bleeding peptic ulcers, large volumes of epinephrine were associated with a reduction in rebleeding. However, the impact of epinephrine volume in patients treated with combination endoscopic therapy remains unclear. AIMTo assess whether epinephrine volume was associated with bleeding outcomes in individuals who also received endoscopic thermal therapy and/or clipping.METHODSData from 132 patients with Forrest class Ia, Ib, and IIa peptic ulcers were reviewed. The primary outcome was further bleeding at 7 d; secondary outcomes included further bleeding at 30 d, need for additional therapeutic interventions, post-endoscopy blood transfusions, and 30-day mortality. Logistic and linear regression and Cox proportional hazards analyses were performed.RESULTSThere was no association between epinephrine volume and all primary and secondary outcomes in multivariable analyses. Increased odds for further bleeding at 7 d occurred in patients with elevated creatinine values (aOR 1.96, 95%CI 1.30-3.20; P < 0.01) or hypotension requiring vasopressors (aOR 6.34, 95%CI 1.87-25.52; P < 0.01). Both factors were also associated with all secondary outcomes.CONCLUSIONEpinephrine maintains an important role in the management of bleeding ulcers, but large volumes up to a range of 10-20 mL are not associated with improved bleeding outcomes among individuals receiving combination endoscopic therapy. Further bleeding is primarily associated with patient factors that likely cannot be overcome by increased volumes of epinephrine. However, in carefully-selected cases where ulcer location or size pose therapeutic challenges or when additional modalities are unavailable, it is conceivable that increased volumes of epinephrine may still be beneficial.

The Clock Is Ticking: The Imminent Need to Re-evaluate the Standard of Care in the 90-Day High-Risk Post-Acute Myocardial Infarction Period

This CSL Behring-supported symposium took place during the European Society of Cardiology (ESC) 2021 Congress. Experts P. Gabriel Steg Cardiology Department, Hôpital Bichat-Claude-Bernard, Paris, France, and the Université de Paris, France; and Kausik Ray, Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, UK; Imperial Clinical Trials Unit, Imperial College London, UK; and Commercial Trials, Imperial College London, UK, discussed the clinical significance of the early post-acute myocardial infarction (AMI) period and the risk of recurrent events despite optimal recommended standard of care. Steg highlighted data from a retrospective registry study as well as several randomised controlled trials, suggesting that recurrent cardiovascular (CV) events appeared to accrue quickly in the early post-AMI period. He proposed that this may be an important timeframe for additional therapeutic interventions and warrants further investigation. Ray highlighted guideline recommendations for secondary prevention, currently focused on lipid-lowering and antiplatelet therapies. Ray presented data from several randomised controlled trials of lipid-lowering therapies, demonstrating that despite therapeutic advances and guideline-recommended treatments, there is a residual risk of recurrent CV events post-AMI. Ray suggested that additional therapeutic targets should be explored to further reduce the incidence of recurrent CV events post-AMI.

Analysis of Apoptotic, Clinical, and Laboratory Parameters in Type 1 Diabetes and Early Diabetic Nephropathy: Clustering and Potential Groups Evaluation for Additional Therapeutic Interventions

Objective:Type 1 diabetes (T1D) is one of the most prevalent chronic illnesses diagnosed in childhood. Diabetic nephropathy (DN) is one of the commonest complication of T1D. Therefore the development of specific treatment that arrests progression of DN based on an individual approach would be beneficial. Analysis of criteria of apoptosis, and clinical, and laboratory characteristics in T1D and early DN in the framework of clustering may be helpful in the identification of potential groups for additional therapeutic interventions.Methods:A survey of 104 children (62 males, 42 females) with T1D and DN aged 2 to 17 years in the Endocrinology unit of Clinical Pediatric Hospital No 6 (Kyiv, Ukraine) was performed. Clinical data (age, gender, disease duration, blood pressure), conventional laboratory markers including complete blood count, serum cholesterol, hemoglobin A1c (Hb1Ac), glomerular filtration rate (GFR), and microalbuminurea (MAU), and markers of apoptosis (BcL-xL, caspase-3) and transcriptional factor HIF-1alfa were analyzed.Results:A cluster group in T1D children was characterized by somewhat higher number of platelets (PLT) - 344.9±7.88·109/L, increased GFR up to hyperfiltration level 124.5±8.86 mL/min/1.73 m2 and decreased anti-apoptotic defense - BcL-xL 144.9±2.35 a.u. was identified. Children with DN may be divided into three groups based on age, body mass index, systolic blood pressure, PLT count, erthyrocyte sedimentation rate, albumin/globulin ratio, serum cholesterol, Hb1Ac, number of diabetic ketoacidosis (DKA) episodes, GFR, MAU, HIF-1alfa, Bcl-xL, caspase-3 levels. Among children with early DN a cluster characterized by the following parameters was found: PLT count - 311.±12.05·109/L, frequency of DKA episodes - 4.82±0.26 episodes/year, MAU - 112.0±10.12 mm/24 h, HIF - 200.5±3.49 a.u., BcL-xL - 128.8±3.1 a.u., and caspase-3 - 159.6±5.5 a.u.Conclusion:Thus, we hypothesize that T1D pediatric patients with increased PLT count, hyperfiltration and reduced anti-apoptotic defense may represent a group for additional therapeutic interventions, such as antioxidants along with stndard therapies to achieve optimal glycemic control. Within the DN group there was a sub-group with somewhat increased PLT count, high frequency of DKA episodes/year, high MAU, prominent increase in HIF level, prominent disturbances in apoptosis controlling factors BcL-xL and caspase-3 tht may require additional therapeutic interventions, again including antioxidants, but may additionally benefit from anti-apoptotic effectors along with optimal glycemic control, and management of hypertension and albuminuria.

Dance movement therapy processes and interventions in the treatment of children with anxiety disorders derived from therapy logs

Dance movement therapy (DMT) offers children a space to encounter strengths and experience a sense of vitality to increase their sense of confidence and self-awareness, thereby easing their anxiety and/or helping them achieve more adaptive emotion regulation. While previous studies indicate that DMT effectively reduces anxiety symptoms, such as stress, scant research focuses on the nature of the therapeutic interventions and how they assist in treating anxiety. This study is a qualitative assessment that examined DMT techniques and interventions of one therapist’s work through their documentation in therapy logs tracking eight long-term treatments of children aged 8–11 coping with anxiety symptoms. Four intervention axes were identified: (1) action-promoting interventions (2) separation-promoting interventions; (3) interventions for strengthening the sense of self; and (4) integration-promoting interventions. Based on the findings, a therapeutic model is proposed drawing on various “mirroring” interventions as the basis for forming the therapeutic relationship and additional therapeutic interventions involving movement. The model enables the child to explore their experience of the relationship, understand themselves in a new way, and create meaning.

Olfactory Loss and Beyond: A Practical Review of Chemosensory Dysfunction.

Our ability to smell and taste is dictated by 3 chemosensory systems with distinct physiologic mechanisms - olfaction, gustation, and chemesthesis. Although often overlooked, dysfunction of these special senses may have broad implications on multiple facets of patients' lives -including safety, nutritional status, quality of life, mental health, and even cognitive function. As "loss of smell or taste" emerged as a common symptom of coronavirus disease 2019 (COVID-19), the importance of intact chemosensory function has been thrust into the spotlight. Despite the growing recognition of chemosensory dysfunction, this already highly prevalent condition will increasingly impact a larger and more diverse population, highlighting the need for improved awareness and care of these patients. Comtemporary review of chemosensory function and assessments. Although patient-reported chemosensory function measures highlight the ease of screening of chemosensory dysfunction, self-reported measures underestimate both the prevalence and degree of chemosensory dysfunction and do not adequately distinguish between olfaction, gustation, and chemesthesis. Meanwhile, psychophysical assessment tools provide opportunities for more accurate, thorough assessment of the chemosenses when appropriate. Primary care providers are uniquely situated to identify patients burdened by chemosensory dysfunction and raise patient and provider awareness about the importance of chemosensory dysfunction. Identification of chemosensory dysfunction, particularly olfactory dysfunction, may raise suspicion for many underlying medical conditions, including early detection of neurodegenerative conditions. Furthermore, identification and awareness of patients with chemosensory dysfunction may help primary care providers to identify those who may benefit from additional therapeutic and safety interventions, or consultations with specialists for more detailed evaluations and management.

Impact of Initial Therapy on Readmissions in Minority Versus White Populations With Heart Failure

Background: Minority populations are often underrepresented in landmark trials for the management of heart failure with reduced ejection fraction (HFrEF). Major trials shaping the guidelines sometimes include as few as 5% black patients. Objective: The purpose of this pilot study was to evaluate the initiation of guideline-directed medical therapy (GDMT) for HFrEF on hospital discharge for minority vs white populations and its impact on all-cause 30-day readmission rates to identify areas for larger future research studies and opportunities for pharmacist intervention. Methods: A retrospective analysis was conducted on patients with HFrEF patients discharged over a 3-month period. The primary objective was to compare all-cause 30-day readmissions in minority vs white patients with HFrEF who were discharged on initial GDMT. Results: 300 patients were included in this study, with 188 patients in the minority group and 112 patients in the white group. The minority group was predominantly African American (92%). The primary endpoint demonstrated significantly higher 30-day all-cause readmissions in minority patients compared to white patients who received initial GDMT (20.5 vs 7.7%, P = .0144), despite similar rates of GDMT therapy between groups. Conclusion: Initial GDMT in minority patients may not reduce readmissions to the same extent seen in white patients. Special emphasis should be placed on evaluating minority patients with HFrEF for additional therapeutic interventions.

Inhibition of Pathological Increased Matrix Metalloproteinase (MMP) Activity for Improvement of Bone Regeneration in Diabetes.

Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db−/db−) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. Mmp3, Mmp9, Mmp13 and gene expression of MMP inhibitor Timp2 was significantly higher in regenerating bone fractures of db−/db− compared to wild type animals. Timp1 and metalloproteinase AdamTS4 showed no differences. In the second part, we locally applied a single dose (1 µL of 5 µM solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db−/db−. We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db−/db− were restored significantly by application of Marimastat compared to PBS controls (n = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes.

Approach to correction of apoptotic disorders in children with early diabetic nephropathy ‎

Diabetic nephropathy is a disease characterized by pathological changes in glomeruli that lead to the development of albuminuria, hypertension, and a decline in renal function. Prominent changes detected in apoptosis controlling factors, i.e. BcL-xL and caspase-3 and require a search for additional non-toxic therapeutic interventions, i.e. antioxidants, anti-apoptotic effectors in addition to glycemic control, hypertension management, as well as albuminuria. The present study included forty-four

Radical or Not-So-Radical Prostatectomy: Do Surgical Margins Matter?

Simple SummaryProstate cancer is the second most common noncutaneous malignancy in men. Prostatectomy is a commonly used treatment modality for selected patients. The prostate’s ill-defined borders and its vicinity with vital structures complicate the wide excision of the organ, resulting in positive margins of resection. Neoplastic infiltration of margins of resection in prostatectomy specimens affects patients’ prognosis. The surgical technique and surgeons’ expertise affect the incidence of margin positivity. The location and the extent of positive margins diversify the risk of recurrence, with basal infiltration and multifocal foci of positive margins behaving more aggressively. Pathologists are encouraged to thoroughly report the status of margins of resection, as they provide important information for patients’ prognosis and enable the clinician to decide upon the most appropriate subsequent therapeutic steps.Prostate cancer is the second most common malignancy in men, and prostatectomy is the treatment of choice for most patients with at least low risk of progression. The presence of positive margins in the radical prostatectomy specimen is considered an adverse pathologic feature, and may prompt additional therapeutic intervention in the patients. The absence of a distinct capsule around the prostate and intraoperative manipulations that aim to minimize postoperative adverse effects, complicate its wide removal. Proper handling of the specimen during the gross processing is essential for accurate determination of the status of margins or resection. Positive margins, defined as the presence of neoplastic glands in the highlighted-with-ink margin of resection, range from 6–38%. The surgical technique, surgeon’s expertise and tumor (i.e., grade and stage) and patients’ (i.e., BMI) characteristics affect the rate of margin positivity. Extensive or multifocal and nonanterior/nonapical positive margins are linked with higher recurrence rates, especially in organ-confined disease, underscoring the need for treating these patients more aggressively. In summary, detailed description of the status of the margins should be performed in every pathology report to determine patients’ prognosis and the most appropriate therapeutic plan.

Therapy Interventions for Upper Limb Amputees Undergoing Selective Nerve Transfers

Targeted Muscle Reinnervation (TMR) improves the biological control interface for myoelectric prostheses after above-elbow amputation. Selective activation of muscle units is made possible by surgically re-routing nerves, yielding a high number of independent myoelectric control signals. However, this intervention requires careful patient selection and specific rehabilitation therapy. Here a rehabilitation protocol is presented for high-level upper limb amputees undergoing TMR, based on an expert Delphi study. Interventions before surgery include detailed patient assessment and general measures for pain control, muscle endurance and strength, balance, and range of motion of the remaining joints. After surgery, additional therapeutic interventions focus on edema control and scar treatment and the selective activation of cortical areas responsible for upper limb control. Following successful reinnervation of target muscles, surface electromyographic (sEMG) biofeedback is used to train the activation of the novel muscular units. Later on, a table-top prosthesis may provide the first experience of prosthetic control. After fitting the actual prosthesis, training includes repetitive drills without objects, object manipulation, and finally, activities of daily living. Ultimately, regular patient appointments and functional assessments allow tracking prosthetic function and enabling early interventions if malfunctioning.

Therapy Interventions for Upper Limb Amputees Undergoing Selective Nerve Transfers.

Targeted Muscle Reinnervation (TMR) improves the biological control interface for myoelectric prostheses after above-elbow amputation. Selective activation of muscle units is made possible by surgically re-routing nerves, yielding a high number of independent myoelectric control signals. However, this intervention requires careful patient selection and specific rehabilitation therapy. Here a rehabilitation protocol is presented for high-level upper limb amputees undergoing TMR, based on an expert Delphi study. Interventions before surgery include detailed patient assessment and general measures for pain control, muscle endurance and strength, balance, and range of motion of the remaining joints. After surgery, additional therapeutic interventions focus on edema control and scar treatment and the selective activation of cortical areas responsible for upper limb control. Following successfulreinnervation of target muscles, surface electromyographic (sEMG) biofeedback is used to train the activation of the novel muscular units. Later on, a table-top prosthesis may provide the first experience of prosthetic control. After fitting the actual prosthesis, training includes repetitive drills without objects, object manipulation, and finally, activities of daily living. Ultimately, regular patient appointments and functional assessments allow tracking prosthetic function and enabling early interventions if malfunctioning.

ADDRESSING CHILDHOOD MALTREATMENT: A PRACTICAL APPROACH FOR THE CHILD PSYCHIATRIST IN A CHANGING HEALTHCARE SYSTEM

Objectives: Childhood maltreatment is a pervasive problem with long-lasting and intergenerational consequences for both mental and physical health. Child and adolescent psychiatrists frequently evaluate youth who are experiencing the lasting effects of maltreatment and should be well-versed in the current recommendations for the assessment, evaluation, and treatment of maltreated children. Methods: Four presentations will examine various aspects of the medical and mental health evaluation of maltreated children and adolescents, evidence-based treatment approaches, and mechanisms of intergenerational transmission. Special consideration will be given to how COVID-19 has affected the experience of maltreated youth and how technology may support or create barriers in the evaluation and treatment of maltreated children and adolescents. Results: The first presentation will focus on approaches to the assessment and evaluation of child maltreatment. The second presentation will address the scope of practice of child abuse pediatrics, including the medical evaluation of suspected abuse, commonly observed injuries, and changes in reporting, prevalence, and evaluation methods that occurred thus far during the COVID-19 pandemic. The third presentation will discuss the evidence base and trauma-informed approaches for the application of psychotherapeutic and psychopharmacologic treatments in survivors of maltreatment. The final presentation will explore the role of the intergenerational transmission of childhood maltreatment on child behavioral and mental health outcomes and will discuss additional therapeutic interventions. Conclusions: Child abuse is a pervasive problem with significant physical and mental health morbidity. Despite the growing recognition of the lasting and intergenerational effects of childhood maltreatment, it is still underrecognized and underreported. The COVID-19 pandemic has influenced both the assessment and treatment of childhood maltreatment as encounters have shifted to virtual settings. It is vital for child and adolescent mental health providers to stay informed of structural changes and evidence-based advances in the diagnosis, protection, evaluation, and treatment of maltreated children. TRA, CAN, EBP

Induction of Robust Type I Interferon Levels by Oncolytic Reovirus Requires Both Viral Replication and Interferon-α/β Receptor Signaling

Oncolytic viruses are promising agents for cancer therapy because they selectively infect and kill tumor cells, and because they trigger immune responses that can boost anticancer immunity. Key to the latter process is the production of type I interferons (IFN-Is) that can turn noninflamed "cold" tumors into "hot" ones. Besides this desired anticancer effect, IFN-Is are antiviral and successful oncolytic virotherapy thus relies on tightly controlled IFN-I levels. This requires a profound understanding of when and how tumor cells induce IFN-I in response to specific viruses. In this study, we uncovered two key factors that augment IFN-I production in transformed human myeloid cells infected with a tumor-selective reovirus. Viral replication and IFN-α/β receptor (IFNAR) signaling progressively reinforced the levels of IFN-I expressed by infected cells. Mechanistically, both augmented the activation of interferon regulatory factor 3, a key transcription factor for IFNβ expression. Our findings imply that reovirus-permissive tumor cells themselves are a major source of IFN-I expression. As tumors can perturb the IFNAR pathway for their own survival, reovirus-exposed IFNAR-unresponsive tumors may need additional therapeutic intervention to promote the secretion of sufficient IFN-I into the tumor microenvironment. Our increased understanding of the parameters that affect reovirus-induced IFN-I levels could aid in the design of tailored virus-based cancer therapies.