Pharmacological strategies to prevent haemodynamic changes after intubation in parturient women with hypertensive disorders of pregnancy: A network meta-analysis

Objective: This network meta-analysis (NMA) aimed to determine the relative efficacy and safety of pharmacological strategies used to mitigate haemodynamic instability by intubation for general anaesthesia in hypertensive parturient women undergoing caesarean section.Methods: We considered randomised controlled studies comparing the effects of pharmacological strategies used to alleviate haemodynamic instability during intubation in parturient women with hypertensive disorders of pregnancy. The primary endpoints were maximum blood pressure and heart rate after intubation, and secondary endpoints were the Apgar scores at 1 and 5 min. NMA allowed us to combine direct and indirect comparisons between strategies.Results: Twelve studies evaluating nine pharmacological strategies in 619 patients were included. According to the surface under the cumulative ranking curve, the maximal mean arterial pressure was lowest for high-dose remifentanil (99.4%) followed by nitroglycerin (73.6%) and labetalol (60.9%). The maximal heart rate was lowest for labetalol (99.9%) followed by high dose of remifentanil (81.2%) and fentanyl (61.6%). Apgar score at 1 min was higher with low-dose than with high-dose remifentanil (mean difference, 0.726; 95% confidence interval, 0.056 to 1.396; I²=0.0%).Conclusions: High-dose remifentanil produces minimum blood pressure changes, while labetalol is most effective in maintaining normal heart rate in parturient women with hypertensive disorders of pregnancy during caesarean section under general anaesthesia.     

Changing Trends in Liver Cirrhosis Etiology and Severity in Korea: the Increasing Impact of Alcohol

BackgroundChronic hepatitis B is the most common cause of liver cirrhosis in South Korea. However, alcoholic liver disease has shown an increasing trend. Although the clinical implications surrounding liver cirrhosis have been changing over the years, few studies have recently examined cirrhosis epidemiology. Therefore, we aimed to investigate changes in liver cirrhosis etiology and severity in Korea.MethodsWe retrospectively reviewed 16,888 records of cirrhotic patients from six tertiary hospitals in Korea from 2008 to 2017. Continuous and non-continuous variables were processed via linear and Poisson regression, expressed as beta (B) coefficients and as exponentiated values of coefficients (Exp[B]), respectively.ResultsChronic hepatitis B showed a decreasing trend (Exp[B] = 0.975, P < 0.001), whereas alcohol showed an increasing trend (Exp[B] = 1.013, P = 0.003), occupying the most common etiology in 2017. The Child-Turcotte-Pugh (CTP) score and decompensated liver cirrhosis prevalence did not change over the 10-year period. The incidence of variceal bleeding, severe ascites, hepatic encephalopathy, and spontaneous bacterial peritonitis significantly decreased from 12.3% to 7.7%, 7.8% to 4.1%, 1.0% to 0.5%, and 1.9% to 1.1%, respectively (P < 0.05 for all). In the subgroup analysis, the chronic hepatitis B group showed improving CTP scores (B = −0.025, P < 0.001) and decreasing decompensated liver cirrhosis rates (Exp[B] = 0.977, P = 0.016), whereas the alcohol group demonstrated increasing CTP class C (Exp[B] = 1.031, P = 0.005) and model for end-stage liver disease scores (B = 0.081, P = 0.005) over 10 years.ConclusionThe chronic hepatitis B group exhibited improved results, whereas the alcohol group still presented poor liver functions and outcomes. Future national policies and systematic approaches addressing the incidence, prevention, and treatment of alcoholic liver cirrhosis are indispensable.     

Developing a Framework for Pandemic COVID-19 Vaccine Allocation: a Modified Delphi Consensus Study in Korea

BackgroundThis study presents a framework for determining the allocation and distribution of the limited amount of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).MethodsAfter analyzing the pandemic strategies of the major organizations and countries and with a literature review conducted by a core panel, a modified Delphi survey was administered to 13 experts in the fields of vaccination, infectious disease, and public health in the Republic of Korea. The following topics were discussed: 1) identifying the objectives of the vaccination strategy, 2) identifying allocation criteria, and 3) establishing a step-by-step vaccination framework and prioritization strategy based on the allocation criteria. Two rounds of surveys were conducted for each topic, with a structured questionnaire provided via e-mail in the first round. After analyzing the responses, a meeting with the experts was held to obtain consensus on how to prioritize the population groups.ResultsThe first objective of the vaccination strategy was maintenance of the integrity of the healthcare system and critical infrastructure, followed by reduction of morbidity and mortality and reduction of community transmission. In the initial phase, older adult residents in care homes, high-risk health and social care workers, and personal support workers who work in direct contact with coronavirus disease 2019 (COVID-19) patients would be prioritized. Expansion of vaccine supply would allow immunization of older adults not included in phase 1, followed by healthcare workers not previously included and individuals with comorbidities. Further widespread vaccine supply would ensure availability to the extended adult age groups (50–64 years old), critical workers outside the health sector, residents who cannot socially distance, and, eventually, the remaining populations.ConclusionThis survey provides the much needed insight into the decision-making process for vaccine allocation at the national level. However, flexibility in adapting to strategies will be essential, as new information is constantly emerging.     

Suppressed estrogen supply via extra-ovarian progesterone receptor membrane component 1 in menopause

In post-menopausal women, intra-mammary estrogen, which is converted from extra-ovarian estrone (E1), promotes the growth of breast cancer. Since the aromatase inhibitor letrozole does not suppress 17β-estradiol (E2) production from E1, high intra-mammary E1 concentrations impair letrozole''s therapeutic efficacy. Progesterone receptor membrane component 1 (Pgrmc1) is a non-classical progesterone receptor associated with breast cancer progression. In the present study, we introduced a Pgrmc1 heterozygous knockout (hetero KO) murine model exhibiting low Pgrmc1 expression, and observed estrogen levels and steroidogenic gene expression. Naïve Pgrmc1 hetero KO mice exhibited low estrogen (E2 and E1) levels and low progesterone receptor (PR) expression, compared to wild-type mice. In contrast, Pgrmc1 hetero KO mice that have been ovariectomized (OVX), including letrozole-treated OVX mice (OVX-letrozole), exhibited high estrogen levels and PR expression. Increased extra-ovarian estrogen production in Pgrmc1 hetero KO mice was observed with the induction of steroid sulfatase (STS). In MCF-7 cell, letrozole suppressed PR expression, but PGRMC1 knockdown increased PR and STS expression. Our presented results highlight the important role of Pgrmc1 in modulating estrogen production when ovary-derived estrogen is limited, thereby suggesting a potential therapeutic approach for letrozole resistance.     

From nonalcoholic fatty liver disease to metabolic-associated fatty liver disease: Big wave or ripple?

There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.     

Impact of an Education Program for Caregivers of Patients with Alzheimer's Disease on Treatment Discontinuation and Compliance in Korea

Background and PurposeReportedly 30–50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer''s disease patients who had newly been prescribed donepezil.MethodsThis multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer''s disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests.ResultsThe donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study.ConclusionsCaregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.     

Decreased 18F-Fluorodeoxyglucose Uptake in Lumbar Vertebrae of Stroke Patients

Background and PurposeWe investigated ¹⁸F-fluorodeoxyglucose (FDG) uptake levels in the lumbar vertebrae, liver, and spleen of stroke patients with carotid atherosclerosis.MethodsThis study analyzed acute ischemic stroke patients with carotid atherosclerosis who underwent whole-body FDG positron-emission tomography between October 2015 and January 2017. FDG uptake in the lumbar vertebrae, liver, and spleen was measured and compared between stroke patients and control subjects without stroke history. Multivariate linear regression analysis was performed to identify independent factors related to FDG uptake in the proximal internal carotid artery (ICA).ResultsTwenty stroke patients aged 75.1±9.0 years (mean±standard deviation; 10 females) and 20 control subjects aged 62.9±10.7 years (6 females) were included. In comparison with the control group, the stroke group showed significantly higher FDG uptake in the proximal ICA (1.16±0.26 vs. 0.87±0.19, p<0.01), but significantly lower FDG uptake in the lumbar vertebrae (1.09±0.26 vs. 1.38±0.38, p=0.007) and liver (1.71±0.30 vs. 2.01±0.34, p=0.005). Multivariate linear regression analysis showed that the lumbar FDG uptake was negatively correlated with FDG uptake in the proximal ICA (standardized coefficient=-0.367, p=0.013) after adjusting for age and hypertension.ConclusionsStroke patients showed decreased FDG uptake in the lumbar vertebrae. Further studies are warranted to evaluate the pathophysiological link between cerebral atherosclerosis and bone.     

Influence of Body Mass Index,Smoking, and Blood Pressure on Survival of Patients with Surgically-Treated,Low Stage Renal Cell Carcinoma: A 14-Year Retrospective Cohort Study

The association of body mass index, smoking, and blood pressure, which are related to the three well-established risk factors of renal cell carcinoma, and survival in patients with renal cell carcinoma is not much studied. Our objective was to evaluate this association. A cohort of 1,036 patients with low stage (pT1 and pT2) renal cell carcinoma who underwent radical or partial nephrectomy were enrolled. We retrospectively reviewed medical records and collected survival data. The body mass index, smoking status, and blood pressure at the time of surgery were recorded. Patients were grouped according to their obesity grade, smoking status, and hypertension stage. Survival analysis showed a significant decrease in overall (P = 0.001) and cancer-specific survival (P < 0.001) with being underweight, with no differences of smoking status or perioperative blood pressure. On multivariate analysis, perioperative blood pressure ≥ 160/100 mmHg (HR, 2.642; 95% CI, 1.221-5.720) and being underweight (HR, 4.320; 95% CI, 1.557-11.984) were independent predictors of overall and cancer-specific mortality, respectively. Therefore, it is concluded that being underweight and perioperative blood pressure ≥ 160/100 mmHg negatively affect cancer-specific and overall survival, respectively, while smoking status does not influence survivals in patients with renal cell carcinoma.     

High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations

Type 1 citrullinemia (CTLN1) often presents as a hyperammonemic encephalopathy in the neonatal period, but it can also develop in the late-infantile period and in adults. In addition, some patients can be identified in the presymptomatic period by neonatal or family member screening. In this study, twenty Korean patients with CTLN1 (19 families) were examined; fourteen patients with neonatal-onset, three with late-onset, and three that were identified presymptomatically. The 13 patients with hyperammonemic encephalopathy received continuous venovenous hemofiltration (CVVH) or peritoneal dialysis (PD). Although the hyperammonemia was relieved more effectively in the six patients on CVVH than the seven on PD, most of these patients suffered from severe neurologic deficits. Recurrent hyperammonemic episodes (7 pts, 35%), recurrent and reversible acute hepatic dysfunction (5 pts, 25%), and focal cerebral infarction (2 pts, 10%) were noted. The neonates with hyperammonemic encephalopathy had extensive brain injuries at the onset of hyperammonemia, followed by encephalomalacia and brain atrophy at quite an early age. Genetic testing for the ASS1 gene revealed a different mutation spectrum from those of other ethnicities; Three common mutations, c.421-2A > G (37.8%), c.1128-6_1188dup67 (18.9%), and p.Gly324Ser (16.2%), accounted for 73% of the mutations. The poor outcome was expected in patients with the peak ammonia level at onset over 600 μmol/L, whose proportion was higher in the neonatal presentation group than in the presymptomatic/late presentation group. Our findings add to the current understanding of the ethnic diversity of CTLN1 from both clinical and genetic perspectives.