Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review

Anorexia nervosa (AN) is a highly complex disorder to treat, especially in severe and enduring cases. Whilst the precise aetiology of the disorder is uncertain, malnutrition and weight loss can contribute to reductions in grey and white matter of the brain, impairments in neuroplasticity and neurogenesis and difficulties with cognitive flexibility, memory and learning. Depression is highly comorbid in AN and may be a barrier to recovery. However, traditional antidepressants are often ineffective in alleviating depressive symptoms in underweight patients with AN. There is an urgent need for new treatment approaches for AN. This review gives a conceptual overview for the treatment of AN with ketamine. Ketamine has rapid antidepressant effects, which are hypothesised to occur via increases in glutamate, with sequelae including increased neuroplasticity, neurogenesis and synaptogenesis. This article provides an overview of the use of ketamine for common psychiatric comorbidities of AN and discusses particular safety concerns and side effects. Potential avenues for future research and specific methodological considerations are explored. Overall, there appears to be ample theoretical background, via several potential mechanisms, that warrant the exploration of ketamine as a treatment for adults with AN.

Antibacterial mechanism of Kratom (Mitragyna speciosa) methanol extract on Streptococcus pneumoniae and Eschericia coli bacteria

Introduction: Kratom (Mitragyna speciosa) is a tropical herbal plant native to the North Malay Peninsula, Malaysia and Thailand. In Indonesia, kratom us a typical plant of West Kalimantan, especially in Putussibau. Kratom leaf has many pharmacological effects, one of them is antioxidant. However, the antioxidant and antimicrobial activities of Mitragyna speciosa leaf extracts are lacking. This study was to examine the effect of the methanol extract of Mitragyna speciosa (Rubiaceae Family) leaves on microorganisms Escherichia coli and Strepococcus pneumoniae.Methods: Kratom leaves were extracted with methanol as solvent. In this study, S. pneumoniae and E. coli bacteria have been used. Antibacterial activity tests were carried out at concentrations of 0.78%, 1.56%, 3.125%, 6.25%, 12.5%, 25%, 50% and 100%. Insilico was used to search for secondary metabolites and metabolite interactions in Mytragina speciosa. Results: Mitragyna speciosa leaf methanol extract was effective in inhibiting the growth of E. coli and S. pneumoniae significantly (P<0.001). The growth of e.coli was not identified from a concentration of 25% to 100%. However, there was no bacterial growth in S. pneumoniae from a concentration of 6.25% to 100%. In the insilico study it was found that the secondary metabolite of Mitragyna speciosa is quercetin, which interacts with the ATP1 protein as a predictor in the mechanism of Mitragyna speciosa as an antibacterial. Conclusion: In conclusion, there is no correlation between nutritional status and remission outcome of patients with ALL in the induction phase of therapy. However, high percentage of underweight patients shows nutrition needs special attention to improve therapy outcomes.

Low Prevalence of Thrombosis Prophylaxis Dose Adjustments Highlights Implications for Patient Safety

Background: Pharmacologic thromboprophylaxis (PTP) is the mainstay prevention strategy for venous thromboembolism (VTE). PTP agents traditionally dosed, like unfractionated heparin (UFH) and enoxaparin (ENOX), are associated with failure and bleeding in obese and underweight patients, respectively. Objectives: This study aimed to describe the prevalence of unadjusted ENOX and UFH dosing for PTP based on anthropometric measures. Patients/Methods: This was a post-hoc, multicenter, cross–sectional analysis of critically ill adults receiving PTP with ENOX or UFH. The primary outcome was the prevalence of unadjusted PTP based on body mass index (BMI) and total body weight (TBW). Definitions for dose adjustments were developed based on existing literature. A secondary outcome was to identify factors associated with unadjusted dosing per BMI and TBW using multivariable generalized linear mixed-effect models. Results: The nested cohort included 172 patients (ENOX=46, UFH=126). Unadjusted PTP was observed in 118 patients (68.6%) based on BMI and 74 (43%) per TBW. When comparing UFH to ENOX, more patients who received UFH had doses unadjusted by BMI (78.6% vs. 41.3%, p<0.05) but not TBW (43.7% vs. 41.3%). Factors independently associated with unadjusted PTP per BMI were receipt of UFH (OR 6.93, 95% CI 1.06-8.77) or a BMI underweight or overweight/obese (OR 10.45, 95% CI 4.38-24.92). Having a TBW <50kg or >100kg (OR 4.85, 95% CI 2.15-10.96) were independently associated with unadjusted PTP based on TBW. Conclusions: Unadjusted dosing of PTP occurs frequently in critically ill adults receiving ENOX or UFH. This was seen in body size extremes by both BMI and TBW.

Both Underweight and Obesity Are Associated With an Increased Risk of Coronavirus Disease 2019 (COVID-19) Severity

Introduction: As coronavirus Disease 2019 (COVID-19) has evolved into a global pandemic, increasing numbers of reports have linked obesity to more severe COVID-19 illness and death. However, almost all the studies focused on an increased risk of mortality or intensive care unit (ICU) admission among hospitalized obese patients with COVID-19. Is obesity also associated with the incidence of acute lung injury (ALI) in the patients with COVID-19? How about underweight patients? The answer is lacking. Therefore, our following research will answer the above two questions.Methods: We collected and analyzed epidemiologic, demographic, clinical, and laboratory data from 193 confirmed cases of COVID-19 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, between January 1, 2020, and March 13, 2020. They were followed up until April 15, 2020. Underweight was defined by body mass index (BMI) lower than 18.5 kg/m2, normal weight by 18.5−23.9 kg/m2, overweight by 24.0−27.9 kg/m2, and obesity as ≥28 kg/m2.Results: Among these patients, 5.70% were underweight, 58.03% were normal weight, 27.98% were overweight, and 8.29% were obese. Underweight patients were more likely to have a headache (P = 0.029). Obese patients were more likely than other groups to experience a decline in lymphocyte counts (P = 0.038), an increase in C-reactive protein (CRP; P = 0.023), bilateral multiple mottling, and ground glass opacity in the lungs (P = 0.007). Besides, the proportion of patients receiving human immunoglobulin + systematic corticosteroids treatment is the highest among the obese group compared with other BMI groups. After adjusting for potential confounders, underweight patients had a 6.483-fold higher (P = 0.012), and obese patients showed a 5.965-fold higher odds for developing ALI than normal-weight patients (P = 0.022). In addition, underweight patients were 3.255 times more likely than normal-weight patients to develop secondary infections (P = 0.041).Conclusions: Our study showed that both underweight and obese patients with COVID-19 tend to develop ALI compared with normal-weight patients. Underweight patients were more likely to develop a secondary infection than other patients.

P01.06 Overweight and obesity as biomarkers for survival outcomes and immune related adverse events undergoing immunotherapy – a systematic review and meta-analysis

BackgroundThe impact of overweight/obesity in cancer patients treated with immune checkpoint inhibitors (ICIs) is controversial. To further contribute to this debate, we performed a systematic review and meta-analysis of published articles evaluating the effects of overweight/obesity on survival and immune-related adverse events (irAEs).Materials and MethodsIn analogy to Cochrane recommendations, systematic literature searches included all published articles in PubMed until February 2021 with key terms ‘obesity’ and ‘overweight’ and ICI treatment irrespective of cancer entity and ICI used. Further selection criteria for meta-analysis included WHO cut-offs for overweight/obesity. For the random effects meta-analysis, we used Hazard Ratios (HR) for overall and progression-free survival (OS, PFS) and Odds Ratios (OR) for occurrence of irAEs with corresponding 95% confidence intervals (95%CI), respectively.ResultsA total of 30 studies (12,895 patients, 38% female) selected for meta-analysis revealed a superior survival of overweight/obese patients (PFS: HR 0.9, 95%CI 0.77-1.04, p = 0.11; OS: 0.74, 95%CI 0.63-0.92, p = 0.0005) compared to normal weight patients. In subgroup analyses based on sex, overweight/obese male patients showed increased survival (PFS: HR 0.79, 95%CI 0.63-1.00, p = 0.05; OS: 0.71, 95%CI 0.58-0.86, p = 0.0005), whereas overweight/obese female patients had similar survival probabilities compared to their normal weight counterparts (PFS: HR 1.01, 95%CI 0.69-1.47, p = 0.96; OS: HR 0.73, 95%CI 0.48-1.10, p = 0.13). Underweight patients showed inferior survival (PFS: HR 1.48, 95%CI 1.07-2.04, p = 0.02; OS: HR 1.86, 95%CI 1.13-3.04, p = 0.01). In addition, overweight/obese patients had a higher risk of developing irAEs with grade ≥ 3 (OR 1.91, 95%CI 1.18-3.10, p = 0.008).ConclusionsOur meta-analysis revealed that overweight/obesity is a beneficial factor for PFS and OS in a mixed cohort of cancer patients undergoing ICI treatment accompanied by an increased risk of severe irAEs. The differences between overweight/obese males and overweight/obese females might point to sex specific adipose distribution patterns and interactions of sex steroids on a molecular level. A significant number of studies included underweight patients into normal weight control groups which led to a compromised interpretation of the data and should be addressed in future studies.Disclosure InformationP. Trinkner: None. S. Günther: None. M. von Bergwelt: None. D. Cordas dos Santos: None. S. Theurich: None.

Stored Energy Increases Body Weight and Skeletal Muscle Mass in Older, Underweight Patients after Stroke

We conducted a retrospective observational study in 170 older, underweight patients after stroke to elucidate whether stored energy was associated with gains in body weight (BW) and skeletal muscle mass (SMM). Energy intake was recorded on admission. The energy requirement was estimated as actual BW (kg) × 30 (kcal/day), and the stored energy was defined as the energy intake minus the energy requirement. Body composition was measured by bioelectrical impedance analysis. The study participants gained an average of 1.0 ± 2.6 kg of BW over a mean hospital stay of 100 ± 42 days with a mean stored energy of 96.2 ± 91.4 kcal per day. They also gained an average of 0.2 ± 1.6 kg of SMM and 0.5 ± 2.3 kg of fat mass (FM). This means about 9600 kcal were needed to gain 1 kg of BW. In addition, a 1 kg increase in body weight resulted in a 23.7% increase in SMM and a 45.8% increase in FM. Multivariate regression analyses showed that the stored energy was significantly associated with gains in BW and SMM. Aggressive nutrition therapy is important for improving nutritional status and function in patients with malnutrition and sarcopenia.

Underweight but not overweight is associated with excess mortality in septic ICU patients

Summary Background Higher survival has been shown for overweight septic patients compared with normal or underweight patients in the past. This study aimed at investigating the management and outcome of septic ICU patients in different body mass index (BMI) categories in a large multicenter database. Methods In total, 16,612 patients of the eICU collaborative research database were included. Baseline characteristics and data on organ support were documented. Multilevel logistic regression analysis was performed to fit three sequential regression models for the binary primary outcome (ICU mortality) to evaluate the impact of the BMI categories: underweight (<18.5 kg/m2), normal weight (18.5 to < 25 kg/m2), overweight (25 to < 30 kg/m2) and obesity (≥ 30 kg/m2). Data were adjusted for patient level characteristics (model 2) as well as management strategies (model 3). Results Management strategies were similar across BMI categories. Underweight patients evidenced higher rates of ICU mortality. This finding persisted after adjusting in model 2 (aOR 1.54, 95% CI 1.15–2.06; p = 0.004) and model 3 (aOR 1.57, 95%CI 1.16–2.12; p = 0.003). No differences were found regarding ICU mortality between normal and overweight patients (aOR 0.93, 95%CI 0.81–1.06; p = 0.29). Obese patients evidenced a lower risk of ICU mortality compared to normal weight, a finding which persisted across all models (model 2: aOR 0.83, 95%CI 0.69–0.99; p = 0.04; model 3: aOR 0.82, 95%CI 0.68–0.98; p = 0.03). The protective effect of obesity and the negative effect of underweight were significant in individuals > 65 years only. Conclusion In this cohort, underweight was associated with a worse outcome, whereas obese patients evidenced lower mortality. Our analysis thus supports the thesis of the obesity paradox.

1514 Higher Mortality in Pelvic Acetabular Fractures Is Associated with Lower Body Mass Index

Aim Fractures of the pelvis and acetabulum can be life-threatening or life changing injuries. Multiple factors can contribute to outcome including age, frailty, and baseline nutritional status. The aim of this study was to identify if low BMI (&lt;18.5) was a predictor of outcome for patients with such injuries in terms of morbidity and mortality. Method We retrospectively analysed 1033 patients with pelvic or acetabular fractures referred to a single level 1 major trauma centre over a 4.5-year period (August 2015 - January 2020). Of these patients, 569 were admitted to the centre and included in our analysis. Data was collected on demographics, injury pattern, operative intervention, and complications. Comparison was made between patients that were underweight (BMI&lt;18.5) and patients that were not, for in-hospital and post discharge complications including pulmonary embolus (PE), deep venous thrombosis (DVT), ileus, infection, loss of reduction and mortality at 6 months. Results Underweight patients had a statistically significant increase in mortality both in-hospital (p = 0.019) and at 6 months post injury (p = 0.039) when compared to other BMI groups. No statistical significance was found between these BMI groups comparing morbidity: DVT (p = 0.712), PE (p = 0.736) nor ileus (p = 0.149). Covariate analysis showed that a low BMI was associated with 3 times increased in-hospital mortality after correction for age and energy of injury (adjusted OR 3.028, 95% CI 1.059-8.659). Conclusions This study suggests increased mortality in patients with pelvic or acetabular fractures who are underweight. Surgeons should consider these findings in initiating appropriate peri-operative optimisation for these patients.

Association between Body Mass Index and Outcomes in Patients with Return of Spontaneous Circulation after Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis

Increased body mass index (BMI) is a risk factor for cardiovascular disease, stroke, and metabolic diseases. A high BMI may affect outcomes of post-cardiac arrest patients, but the association remains debatable. We aimed to determine the association between BMI and outcomes in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). A systematic literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library. Studies that included patients who presented ROSC after OHCA, had a recorded BMI, and were assessed for neurological outcomes and in-hospital mortality were included. To assess the risk of bias of each included study, we employed the Risk of Bias Assessment Tool for Non-randomized Studies. We assessed 2427 patients from six studies. Neurological outcomes were significantly poorer in underweight patients (risk ratio (RR) = 1.21; 95% confidence interval (CI) = 1.07–1.37; p = 0.002; I2 = 51%) than in normal-weight patients. Additionally, in-hospital mortality rate was significantly higher in underweight patients (RR = 1.35; 95% CI = 1.14–1.60; p<0.001; I2 = 21%) and in obese patients (RR = 1.25; 95% CI = 1.12–1.39; p<0.001; I2 = 0%) than in normal-weight patients. Poor neurological outcome is associated with underweight, and low survival rate is associated with underweight and obesity in patients with ROSC after OHCA.

Comprehensive Analysis of Chemotherapeutic Agents THAT Induce Infectious Neutropenia

Chemotherapy-induced neutropenia (CIN) has been associated with a risk of infections and chemotherapy dose reductions and delays. The chemotherapy regimen remains one of the primary determinants of the risk of neutropenia, with some regimens being more myelotoxic than others. Although a number of clinical trials have currently highlighted the risk of CIN with each chemotherapy regimen, only a few ones have comprehensively examined the risk associated with all chemotherapeutic agents. Therefore, this study aimed to investigate the risk factors and characteristics of CIN caused by each neoplastic agent using data from the large voluntary reporting Food and Drug Administration Adverse Event Reporting System database. Initially, univariate analysis showed that an age ≥ 65 years, the female sex, and treatment with chemotherapeutic agents were factors that caused CIN. Then, cluster and component analyses showed that cytotoxic agents (i.e., alkylating agents, antimetabolic agents, antineoplastic antibiotics, platinating agents, and plant-derived alkaloids) were associated with infection following neutropenia. This comprehensive analysis comparing CIN risk suggests that elderly or underweight patients treated with cytotoxic drugs require particularly careful monitoring.