Timing of Vasopressin Addition to Norepinephrine and Efficacy Outcomes in Patients With Septic Shock.

BACKGROUND: Current guidelines recommend norepinephrine as the first-line vasopressor in septic shock followed by addition of vasopressin to achieve a goal mean arterial pressure. Limited evidence exists evaluating how the timing of vasopressin addition affects clinical outcomes in septic shock. OBJECTIVE: The objective of this study was to determine whether the timing of the addition of vasopressin to norepinephrine affects shock resolution. METHODS: This was a multi-site, single system, retrospective cohort, institutional review board (IRB)-approved study examining adult patients with septic shock who received norepinephrine and vasopressin. Patients were divided and statistically analyzed in two subgroups: early vasopressin addition (<3 hours) and late vasopressin addition (≥3 hours). The primary outcome was time to shock resolution, defined as vasopressor free for at least 24 hours. Secondary outcomes included norepinephrine dose at 3 hours after initiation of vasopressin, in-hospital mortality, and intensive care unit length of stay. RESULTS: A total of 243 patients were included in this study. A statistically significant decrease in time to shock resolution was observed in the early vasopressin addition group compared to the late vasopressin addition group (37.6 hours vs 60.7 hours; adjusted hazard ratio [HR]: 2.07 [1.48-2.89; P = <0.001]). The early addition of vasopressin did not affect norepinephrine dose or in-hospital mortality but did lead to a decreased intensive care unit (ICU) length of stay (4.3 days vs 5.3 days, P = 0.02). CONCLUSION AND RELEVANCE: Addition of vasopressin to norepinephrine within 3 hours was associated with a faster time to shock resolution. These findings suggest a potential for improved clinical outcomes with earlier vasopressin addition.

Disclosure of lived experience of mental illness in training: Reasons for disclosure.

Students in mental health (MH) professions often face MH symptoms themselves related to the stress of graduate training and have been shown to benefit from supportive mentoring. Little is known, however, about trainees who already have a mental illness, and how best to help them succeed. Snowball sampling was used to survey 35 MH professionals with lived experience of mental illness (LE), also known as "prosumers." The survey included questions about participants' past disclosure about mental illness when they were in a training role. Questions were also asked about participants' experience supervising or teaching students who had disclosed LE. The survey included quantitative and qualitative data. Of participants who disclosed experiences of mental illness during past training, most disclosed to a clinical supervisor, with the most common reason for disclosure being to seek social support. A majority (83%) of those who endorsed having a trainee disclose to them were "out" about their own LE at the time. The majority of participants (78%) indicated they would like accessible examples of how others had dealt with trainee disclosure to use as a tool in working with trainees. We conclude with implications for future research and resources on this topic. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Workplace bullying among mental health providers with lived experience of a mental health challenge.

Mental health care providers who have a personal lived experience of mental health challenges are valuable employees who may be vulnerable to workplace bullying, which causes harm both to these individuals and to their organizations. We used snowball sampling to survey 40 mental health professionals with lived experience about their history of workplace bullying and whether or not their lived experience was known ("out") or concealed ("closeted"). We found that our sample experienced workplace bullying at much higher rates than published samples from the general population. More than three-quarters of our sample reported having ever experienced bullying and almost half had been bullied in the past year. Furthermore, most of those who had ever experienced bullying reported having been closeted at the time. Further exploratory analyses identified some specific aspects of bullying that might be fruitful areas for future research. We conclude with implications for employee recruitment and retention, vocational rehabilitation, and organizational development. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Low-frequency exercise training improves cardiovascular fitness and strength during treatment for breast cancer: a single-arm intervention study.

Aerobic and resistance exercise during and after cancer treatment are important for health-related outcomes, however treatment-specific barriers may inhibit adherence. We explored the effect of lower-frequency exercise training on fitness, body composition, and metabolic markers (i.e. glucose and lipids) in a group of recently diagnosed breast cancer patients. Fifty-two females ≥ 18 years with stage I-IIIB breast cancer were instructed to attend 2 cardiovascular and strength training sessions/week over 12 weeks, but program length was expanded as needed to accommodate missed sessions. Pre- and post-intervention, we measured: (1) cardiovascular fitness, (2) isometric strength, (3) body composition (dual-energy X-ray absorptiometry), and (4) fasting glucose, insulin, c-peptide, and lipids. Pre-intervention, participants were 53 ± 10 years old (mean ± SD) and overweight (BMI: 27.5 ± 5.4 kg m-2, 40.1 ± 6.5% body fat). Forty participants completed the program over a median 20 weeks (range: 13-32 weeks, median frequency: 1.2 sessions/week), over which predicted VO2peak improved by 7% (2.2[0.1-4.4] mL/kg/min) (delta[95% CI]), and strength increased by 7-9% (right arm: 2.3[0.1-4.5] N m; right leg: 7.9[2.1-13.7] N m; left leg: 7.8[1.9-13.7] N m). Body composition and metabolic markers were unchanged. An exercise frequency of 1.2 sessions/week stimulated significant improvements in fitness, and may represent a practical target for patients during active treatment.

Glutamate increases glucose uptake in L6 myotubes in a concentration- and time-dependent manner that is mediated by AMPK.

Various in vivo studies have investigated the insulin response that is elicited when glutamate is elevated in circulation or in a given tissue; fewer studies have investigated the effects of glutamate on glucose uptake and handling. Glutamate ingestion in humans can attenuate rises in blood glucose following a carbohydrate load in the absence of increases in serum insulin concentrations. However, the underlying mechanisms have yet to be investigated. To elucidate the effects of glutamate on glucose handling in skeletal muscle tissue, differentiated rat L6 myocytes were treated with glutamate, and glucose uptake was assessed with the use of 2-[3H]-deoxy-d-glucose ([3H]-2-DG). Cells treated with 2 mmol/L glutamate experienced the greatest increase in [3H]-2-DG uptake relative to the control condition (177% ± 2% of control, P < 0.001) and the uptake was similar to that of metformin (184% ± 4%, P < 0.001). In line with these findings, differentiated glucose transporter 4 (GLUT4)-overexpressing myotubes treated with 2 mmol/L glutamate displayed significantly increased GLUT4 translocation when compared with the control condition (159% ± 8% of control, P < 0.001) and to an extent similar to that of insulin and metformin (181% ± 7% and 159% ± 12%, respectively). An AMP-activated protein kinase (AMPK) inhibitor (Compound C) abolished the glutamate-stimulated glucose uptake (98% ± 12% of control), and Western blotting revealed significantly elevated AMPK phosphorylation (278% ± 17% of control, P < 0.001) by glutamate. Our findings suggest that when muscle cells are exposed to increased glutamate concentrations, glucose uptake into these cells is augmented through AMPK activation, through mechanisms distinct from those of insulin and leucine.

Necrotizing Esophagitis and Bleeding Associated With Cefazolin.

OBJECTIVE: To report the case of a patient who presented with rare necrotizing esophagitis related to cefazolin-associated coagulopathy. A review of the literature is also provided. CASE SUMMARY: A 53-year-old male patient was admitted for management of septicemia and femur osteomyelitis. Long-term cefazolin treatment was initiated after cultures and sensitivity revealed methicillin-sensitive Staphylococcus aureus. The patient was given intravenous cefazolin 2 g every 24 hours. On day 15 of cefazolin treatment, the patient presented to the emergency department complaining of black coffee ground emesis. On upper-gastrointestinal endoscopy, the patient was determined to have necrotizing esophagitis. He was found to have an international normalized ratio (INR) of 8.11 and prothrombin time (PT) of 89.2 s. Intravenous vitamin K, fresh frozen plasma, and packed red blood cells were administered. The INR was rechecked 4 hours later and found to have decreased to 1.55 with a PT of 17 s. The patient did not have medical conditions or take medications that could have caused bleeding. DISCUSSION: Based on the Naranjo algorithm, it was determined that cefazolin had a "probable" relationship. Increased bleeding risk has been associated with other cephalosporins, although much less commonly with cefazolin. Possible mechanisms and implications are discussed. CONCLUSIONS: High-risk patients being treated with cefazolin therapy should be monitored for potentially severe adverse events, including bleeding and necrotizing esophagitis.

Plasma amino acid profiles of breast cancer patients early in the trajectory of the disease differ from healthy comparison groups.

This study describes and compares fasting plasma amino acid profiles of breast cancer patients near the initiation of chemotherapy with those of healthy age- and body mass index-matched females (HM), as well as young healthy females (HY). Breast cancer patients had significantly greater glutamate and histidine concentrations and significantly lower threonine concentrations compared with HM and HY females independent of protein or caloric intake. These differences may be related to metabolic perturbations associated with the disease.

Glutamate supplementation is associated with improved glucose metabolism following carbohydrate ingestion in healthy males.

Glutamate is linked to the glycolytic process, particularly when co-ingested with carbohydrate, but its effects on glucose metabolism are poorly characterised. The present study aimed to (1) specifically examine the effects of carbohydrate administration on circulating glutamate concentrations and (2) investigate the effect of increased glutamate availability, independent of carbohydrate ingestion, on glucose metabolism. A total of nine participants underwent four trials: (1) glutamate supplement+carbohydrate drink (GLU+CHO); (2) glutamate supplement+placebo drink (GLU); (3) placebo supplement+carbohydrate drink (CHO); (4) placebo supplement+placebo drink (CON). Following a fasting blood sample, participants ingested monosodium L-glutamate (MSG; 150 mg/kg body weight) or placebo capsules at each trial followed by a 75 g carbohydrate or a non-energy placebo drink 30 min later. Blood samples were taken at 0, 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 min. Plasma glutamate concentrations were significantly elevated relative to baseline during the GLU (approximately 10-fold) and GLU+CHO trials (approximately 6-fold). The glucose response to a carbohydrate load was blunted when glutamate was increased in the circulation (peak serum glucose: 5.50 (SE 0.54) mmol/l during the GLU+CHO trial v. 7.69 (SE 0.53) mmol/l during the CHO trial, P< 0.05). On average, c-peptide results revealed that insulin secretion did not differ between the GLU+CHO and CHO trials; however, four participants demonstrated increased insulin secretion during the GLU+CHO trial and five participants demonstrated decreased insulin secretion under the same conditions. In conclusion, when administration is staggered, MSG and carbohydrate supplementation can be used to manipulate plasma glutamate; however, future studies should control for this dichotomous insulin response.