JAMA Intern Med. 2024 Mar 18. doi: 10.1001/jamainternmed.2024.0136. Online ahead of print.
NO ABSTRACT
PMID:38497973 | DOI:10.1001/jamainternmed.2024.0136
JAMA Neurol. 2024 Mar 18. doi: 10.1001/jamaneurol.2024.0126. Online ahead of print.
ABSTRACT
IMPORTANCE: Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy.
OBJECTIVE: To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD).
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023.
MAIN OUTCOMES AND MEASURES: MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features.
RESULTS: Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P < .001, and 3/4 patients [75%] with CJD; P = .005), less frequently exhibited swelling (12/55 [22%] with LGI1/CASPR2-Ab-E vs 13/22 [59%] with VE; P = .003), and showed no diffusion restriction (0 patients vs 16/22 [73%] with VE and 8/10 [80%] with CJD; both P < .001) and rare contrast enhancement (1/20 [5%] vs 7/17 [41%] with VE; P = .01). These findings were validated in an independent cohort and generated an area under the curve of 0.97, sensitivity of 90%, and specificity of 95% among cases with T2/FLAIR hyperintensity in the hippocampus and/or amygdala.
CONCLUSIONS AND RELEVANCE: In this study, T2 and/or FLAIR hyperintensities confined to the temporal lobes, without diffusion restriction or contrast enhancement, robustly distinguished LGI1/CASPR2-Ab-E from key differential diagnoses. These observations should assist clinical decision-making toward expediting immunotherapy. Their generalizability to other forms of autoimmune encephalitis and VE should be examined in future studies.
PMID:38497971 | DOI:10.1001/jamaneurol.2024.0126
JAMA Netw Open. 2024 Mar 4;7(3):e240988. doi: 10.1001/jamanetworkopen.2024.0988.
ABSTRACT
IMPORTANCE: Isolated tumor cells (ITCs) are the histopathological finding of small clusters of cancer cells no greater than 0.2 mm in diameter in the regional lymph nodes. For endometrial cancer, the prognostic significance of ITCs is uncertain.
OBJECTIVE: To assess clinico-pathological characteristics and oncologic outcomes associated with ITCs in endometrial cancer.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study using the National Cancer Database included patients with endometrial cancer who had primary hysterectomy and nodal evaluation from 2018 to 2020. Patients with microscopic and macroscopic nodal metastases and distant metastases were excluded. Data were analyzed from June to September 2023.
EXPOSURE: Regional nodal status with ITCs (N0[i+] classification) or no nodal metastasis (N0 classification).
MAIN OUTCOMES AND MEASURES: (1) Clinical and tumor characteristics associated with ITCs, assessed with multivariable binary logistic regression model, and (2) overall survival (OS) associated with ITCs, evaluated by nonproportional hazard analysis with restricted mean survival time at 36 months.
RESULTS: A total of 56 527 patients were included, with a median (IQR) age of 64 (57-70) years. The majority had T1a lesion (37 836 [66.9%]) and grade 1 or 2 endometrioid tumors (40 589 [71.8%]). ITCs were seen in 1462 cases (2.6%). In a multivariable analysis, ITCs were associated with higher T classification, larger tumor size, lymphovascular space invasion (LVSI), and malignant peritoneal cytology. Of those tumor factors, LVSI had the largest association with ITCs (7.9% vs 1.4%; adjusted odds ratio [aOR], 4.37; 95% CI, 3.87-4.93), followed by T1b classification (5.3% vs 1.3%; aOR, 2.62; 95% CI, 2.30-2.99). At the cohort level, 24-month OS rates were 94.3% (95% CI, 92.4%-95.7%) for the ITC group and 96.1% (95% CI, 95.9%-96.3%) for the node-negative group, and the between-group difference in expected mean OS time at 36 months was 0.35 (SE, 0.19) months, but it was not statistically significant (P = .06). There was a statistically significant difference in OS when the low-risk group (stage IA, grade 1-2 endometrioid tumors with no LVSI) was assessed per nodal status and adjuvant therapy use (P < .001): (1) among the cases treated with surgical therapy alone, 24-month OS rates were 95.9% (95% CI, 89.5%-98.5%) for the ITC group and 98.8% (95% CI, 98.6%-99.0%) for the node-negative group, and the between-group mean OS time difference at 36 months was 0.61 (SE, 0.43) months (P = .16); and (2) among the cases with ITCs, adjuvant therapy (radiotherapy alone, systemic chemotherapy alone, or both) was associated with improved survival compared with no adjuvant therapy (24-month OS rates, 100% vs 95.9%; between-group mean OS time difference at 36 months, 0.95 [SE, 0.43] months; P = .03).
CONCLUSIONS AND RELEVANCE: In this cohort study of patients with surgically staged endometrial cancer, the results of exploratory analysis suggested that presence of ITCs in the regional lymph node may be associated with OS in the low-risk group. While adjuvant therapy was associated with improved OS in the low-risk group with ITCs, careful interpretation is necessary given the favorable outcomes regardless of adjuvant therapy use. This hypothesis-generating observation in patients with low-risk endometrial cancer warrants further investigation, especially with prospective setting.
PMID:38497964 | DOI:10.1001/jamanetworkopen.2024.0988
JAMA Netw Open. 2024 Mar 4;7(3):e242732. doi: 10.1001/jamanetworkopen.2024.2732.
ABSTRACT
IMPORTANCE: Agonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone.
OBJECTIVE: To evaluate postrelease outcomes after buprenorphine implementation.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024.
EXPOSURE: April 2019 implementation of buprenorphine during incarceration.
MAIN OUTCOMES AND MEASURES: Receipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation.
RESULTS: A total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected.
CONCLUSIONS AND RELEVANCE: In this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.
PMID:38497959 | DOI:10.1001/jamanetworkopen.2024.2732
JAMA Intern Med. 2024 Mar 18. doi: 10.1001/jamainternmed.2024.0001. Online ahead of print.
ABSTRACT
IMPORTANCE: Increasing influenza vaccination rates is a public health priority. One method recommended by the US Centers for Disease Control and Prevention and others is for health systems to send reminders nudging patients to be vaccinated.
OBJECTIVE: To evaluate and compare the effect of electronic health record (EHR)-based patient portal reminders vs text message reminders on influenza vaccination rates across a health system.
DESIGN, SETTING, AND PARTICIPANTS: This 3-arm randomized clinical trial was conducted from September 7, 2022, to April 30, 2023, among primary care patients within the University of California, Los Angeles (UCLA) health system.
INTERVENTIONS: Arm 1 received standard of care. The health system sent monthly reminder messages to patients due for an influenza vaccine by portal (arm 2) or text (arm 3). Arm 2 had a 2 × 2 nested design, with fixed vs responsive monthly reminders and preappointment vs no preappointment reminders. Arm 3 had 1 × 2 design, with preappointment vs no preappointment reminders. Preappointment reminders for eligible patients were sent 24 and 48 hours before scheduled primary care visits. Fixed reminders (in October, November, and December) involved identical messages via portal or text. Responsive portal reminders involved a September message asking patients about their plans for vaccination, with a follow-up reminder if the response was affirmative but the patient was not yet vaccinated.
MAIN OUTCOMES AND MEASURES: The primary outcome was influenza vaccination by April 30, 2023, obtained from the UCLA EHR, including vaccination from pharmacies and other sources.
RESULTS: A total of 262 085 patients (mean [SD] age, 45.1 [20.7] years; 237 404 [90.6%] adults; 24 681 [9.4%] children; 149 349 [57.0%] women) in 79 primary care practices were included (87 257 in arm 1, 87 478 in arm 2, and 87 350 in arm 3). At the entire primary care population level, none of the interventions improved influenza vaccination rates. All groups had rates of approximately 47%. There was no statistical or clinically significant improvement following portal vs text, preappointment reminders vs no preappointment reminders (portal and text reminders combined), or responsive vs fixed monthly portal reminders.
CONCLUSIONS AND RELEVANCE: At the population level, neither portal nor text reminders for influenza vaccination were effective. Given that vaccine hesitancy may be a major reason for the lack of impact of portal or text reminders, more intensive interventions by health systems are needed to raise influenza vaccination coverage levels.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05525494.
PMID:38497955 | DOI:10.1001/jamainternmed.2024.0001
Pharm Dev Technol. 2024 Mar 18:1-17. doi: 10.1080/10837450.2024.2331243. Online ahead of print.
ABSTRACT
In this work we exploit Computational Fluid Dynamics (CFD) to evaluate Stirred Tank Reactor (STR) Process Engineer Parameters (PEP) and design a scale down system (SDS) to be representative of the formulation and filling process steps for an Aluminum adjuvanted vaccine Drug Product (DP). To study the shear history in the SDS we used the concept of number of passages, combined with an appropriate stirring speed down scale strategy comprising of either i) Tip speed equivalence, widely used as scale-up criterion for shear-sensitive product, or ii) Rotating shear, a shear metric introduced by Metz and Otto in 1957 but never used as scaling criterion. The outcome of the CFD simulations shows that the tip equivalence generates a worst case SDS in terms of shear, whereas the rotating shear scaling approach could be used to design more representative SDS. We monitored the trend over time for “In Vitro Relative Potency” as DP Critical Quality Attribute for both scaling approaches, which highlighted the crucial role of choosing the appropriate scaling down approach to be representative of the manufacturing scale during process characterization studies.
PMID:38497925 | DOI:10.1080/10837450.2024.2331243
Eur Rev Med Pharmacol Sci. 2024 Mar;28(5):2107-2116. doi: 10.26355/eurrev_202403_35623.
ABSTRACT
OBJECTIVE: This study aimed to determine the effect of tocilizumab use on mortality and the potential side effects in COVID-19 patients.
PATIENTS AND METHODS: The intensive care patients were divided into the tocilizumab group and the control group. Hemogram, biochemistry, acute phase reactant values, age, gender, comorbidity, and culture results were recorded on the 0th, 3rd, 7th, and 14th days. Factors affecting mortality between and within the groups and side effects were examined.
RESULTS: 32.14% of the patients were female, and 67.85% were male. The tocilizumab group had high alanine aminotransferase and potassium on day 3. On day 7, low levels of platelet, glucose, international normalized ratio, prothrombin time, and active partial thromboplastin time levels were observed. Procalcitonin, C-reactive protein, and fibrinogen levels were low on days 3 and 7. The relationship between the tocilizumab treatment and mortality was statistically not significant, although the APACHE score was low. In the tocilizumab group, the presence of additional disease and reproduction in culture significantly increased mortality.
CONCLUSIONS: Despite the risks of side effects, tocilizumab was used in COVID-19 treatment since it is an interleukin-6 blocker. Although the first publications stated that the treatment could decrease the mortality rate, later meta-analyses did not support these results. Our study also found that using tocilizumab did not make a difference in long-term mortality. We also observed that the known side effects were seen in short-term use.
PMID:38497892 | DOI:10.26355/eurrev_202403_35623
Eur Rev Med Pharmacol Sci. 2024 Mar;28(5):2005-2013. doi: 10.26355/eurrev_202403_35615.
ABSTRACT
OBJECTIVE: Uncarboxylated osteocalcin is an important osteocalcin enzyme found in the bloodstream and is a crucial protein for maintaining calcium binding in bones, controlling blood sugar levels, and balancing body minerals.
PATIENTS AND METHODS: Due to the lack of data, the current study intends to investigate the relationship between uncarboxylated osteocalcin levels and DM-II in Saudi patients. For 138 patients, case-control research was conducted in 2021-2023, with 69 type II diabetes mellitus patients and 69 matching healthy control participants. An enzyme immunoassay kit was used to quantify the levels of uncarboxylated osteocalcin in fasting blood samples, and an automated analyzer evaluated Hb1Ac, fasting blood glucose, enzymes, electrolytes, lipid, and kidney profiles. Data processing and analysis were carried out using GraphPad Prism statistical software.
RESULTS: According to our study, patients with type II diabetes mellitus had considerably lower levels of uncarboxylated osteocalcin than healthy controls. According to the correlation analysis, uncarboxylated osteocalcin and fasting blood sugar had a negative relationship. In the overweight BMI group, uncarboxylated osteocalcin was considerably higher in control subjects.
CONCLUSIONS: We concluded that, in Saudi type II diabetes mellitus patients, the compromised glucose level is associated with diminished serum uncarboxylated osteocalcin. This study has limitations, such as a small sample size and only measuring the uncarboxylated form of plasma osteocalcin. Future research is needed to understand how anti-diabetic drugs affect undercarboxylated osteocalcin’s effect on metabolic control and provide more efficient techniques and resources in diabetes and osteoporosis prevention and care.
PMID:38497883 | DOI:10.26355/eurrev_202403_35615
Eur Rev Med Pharmacol Sci. 2024 Mar;28(5):1937-1946. doi: 10.26355/eurrev_202403_35608.
ABSTRACT
OBJECTIVE: Cerebral ischemia (CI) is a condition in which metabolic stress increases when blood flow is interrupted in a part of the brain, resulting in oxygen and glucose deprivation. It is known that asprosin (Asp), secreted from adipose tissue during fasting, has an effect on some metabolic processes such as apoptosis, autophagy, and glucose metabolism. This study aimed to explain which of the cell death/survival Asp induces in the CI/reperfusion model.
MATERIALS AND METHODS: In the study, 48 male Wistar Albino rats were divided into 6 groups: Sham, CI, Asp+CI, CI+Asp, CI+Asp+3-MA, and Asp+CI+3-MA (n=48). CI was created using the intraluminal filament technique for 60 minutes, autophagy inhibitor 3-MA (15 mg/kg/day) and Asp (1 µg/kg/day) injections were administered 3 days before or 3 days during reperfusion. Beclin-1, ATG5, ATG7, p62, Bcl-2, Bax, active-caspase-3, and active-caspase-9 protein levels from brain tissues were determined by the Western-Blot method. The infarct area was determined by triphenyl tetrazolium chloride (TTC) staining. The Kruskal-Wallis’ test was used to compare differences between groups. p<0.05 was considered statistically significant.
RESULTS: Compared to the Sham group, the increase in ischemic area and the decrease in Beclin-1, ATG-5, ATG-7, Bcl-2, Bax, active-caspase-3 and active-caspase-9 levels in the CI groups are statistically significant (p<0.05). The increase of Beclin-1, ATG-7, Bcl-2, and Bax levels in the Asp groups is statistically significant compared to the CI group (p<0.05). When Asp+CI groups and CI+Asp groups are compared, an increase in Beclin-1 levels in the Asp+CI group and the increase in Bcl-2, Bax, active-caspase-3/9 and ATG-5 levels in the CI+Asp groups are statistically significant (p<0.05).
CONCLUSIONS: Asp has protective and therapeutic effects against CI/R damage. While applying Asp before ischemia activates the autophagy pathway more, applying it after ischemia protects the neuronal death/survival balance by activating the apoptosis pathway more.
PMID:38497877 | DOI:10.26355/eurrev_202403_35608
Eur Rev Med Pharmacol Sci. 2024 Mar;28(5):1931-1936. doi: 10.26355/eurrev_202403_35607.
ABSTRACT
OBJECTIVE: The autonomic nervous system (ANS) plays an important role in maintaining physiological regulation. It regulates the body’s response to many variable situations. Orthostatic intolerance (OI) is one of the most important signs of autonomic dysfunction. Autonomic dysfunction is known to cause premature ejaculation (PE) by disturbing the balance in erection and ejaculation cycles. Considering that OI may develop due to autonomic dysfunction in patients with PE, we hypothesized that OI symptoms would increase in these patients. The aim of our study was to investigate the relationship between orthostatic intolerance and PE.
PATIENTS AND METHODS: This case-control study included a total of 39 patients with PE and 47 volunteers without PE. All subjects were assessed using the self-reported Orthostatic Grading Scale (OGS). In addition, the validated five-item Turkish version of the Premature Ejaculation Diagnostic Tool (PEDT) was used to evaluate PE. The PE group included patients with a PEDT score ≥ 11.
RESULTS: The mean ages of the PE and control groups were 38.2 ± 7.8 and 40.5 ± 9.1 years, respectively (p = 0.137). The mean PEDT scores of the PE and control groups were 13.9 ± 3.6 and 6.6 ± 2.9, respectively (p < 0.0001), and their mean OGS scores were 5.6 ± 2.4 and 1.6 ± 1.3, respectively (p < 0.0001). A statistically significant correlation was found between the PEDT and OGS scores (r: 0.686, p < 0.0001).
CONCLUSIONS: The orthostatic intolerance symptoms of patients with PE were higher than those of the control group. There was a correlation between the severity of PE and the severity of orthostatic intolerance. This is the first study in the literature to reveal a relationship between orthostatic intolerance and PE.
PMID:38497876 | DOI:10.26355/eurrev_202403_35607