bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of patients with HCC and liver dysfunction under immunotherapy: a systematic review and meta-analysis
Authors: El Hajra Ismael , Sanduzzi-Zamparelli Marco , Sapena Víctor , Muñoz-Martínez Sergio , Mauro Ezequiel , Llarch Neus , Iserte Gemma , Forner Alejandro , Rios José , Bruix Jordi , Reig María
Published: January 2023

Background and Aims:

Immunotherapy-based regimes have changed the management of HCC. However, evidence of efficacy in patients with impaired liver function is unknown. This systematic review and meta-analysis assesses survival of HCC patients and liver dysfunction treated with immunotherapy-based regimens.

Methods:

Systematic review and meta-analysis of original articles or abstracts reporting survival of HCC patients treated with immunotherapy according to liver function between 2017 and 2022. Overal survival (OS) according to restricted mean survival time (RMST) and median OS, and hazard ratio (HR) of Child-Pugh B or B/C versus Child-Pugh A were assessed while considering the line of treatment.

Results:

Of the 2218 articles considered, 15 articles recruiting 2311 patients were included. Of these, 639 (27.7%) were Child-Pugh B and 34 (1.5%) C. RMST was 8.36 (95% CI, 6.15–10.57; I
2=93%) months, estimated from 8 studies. The HR was reported in 8 studies for survival between Child-Pugh B versus Child-Pugh A and metanalysis disclosed a 1.65 HR (95% CI,1.45–1.84; I
2=0% heterogeneity; p = 0.45). Treatment line data were available for 47% of the patients and 3 studies included patients treated with atezolizumab-bevacizumab in the first line.

Conclusions:

The high heterogeneity across studies reflects the incapacity of the current evidence to support the indication of immunotherapy in HCC patients with relevant liver dysfunction. It is mandatory to report complementary information to Child-Pugh classification such as prior liver decompensation, use of concomitant medication to control ascites, or signs of clinically significant portal hypertension to allow better patient stratification in future studies.
Outcome of untreated low-level viremia versus antiviral therapy-induced or spontaneous undetectable HBV-DNA in compensated cirrhosis
Authors: Huang Daniel Q. , Tamaki Nobuharu , Lee Hyung Woong , Park Soo Young , Lee Yu Rim , Lee Hye Won , Lim Seng Gee , Lim Tae Seop , Kurosaki Masayuki , Marusawa Hiroyuki , Mashiba Toshie , Kondo Masahiko , Uchida Yasushi , Kobashi Haruhiko , Furuta Koichiro , Izumi Namiki , Kim Beom Kyung , Sinn Dong Hyun
Published: January 2023

Background:

Comparative outcomes of HBV-infected compensated cirrhosis with low-level viremia (LLV) versus maintained virological response (MVR) are unclear. We conducted a large, multiethnic, multicenter study to examine the natural history of LLV versus MVR in compensated cirrhosis.

Patients and Methods:

We enrolled patients with HBV-infected compensated cirrhosis (n=2316) from 19 hospitals in South Korea, Singapore, and Japan. We defined the LLV group as untreated patients with ≥1 detectable serum HBV-DNA (20–2000 IU/mL), Spontaneous-MVR group as untreated patients with spontaneously achieved MVR, and antiviral therapy (AVT)-MVR group as patients achieving AVT-induced MVR. Study end points were HCC or hepatic decompensation.

Results:

The annual HCC incidence was 2.7/100 person-years (PYs), 2.6/100 PYs, and 3.3/100 PYs for LLV (n=742), Spontaneous-MVR (n=333), and AVT-MVR (n=1241) groups, respectively (p = 0.81 between LLV vs. Spontaneous-MVR groups and p = 0.37 between LLV vs. AVT-MVR groups). Similarly, the annual decompensation incidence was 1.6/100 PYs, 1.9/100 PYs, and 1.6/100 PYs for LLV, Spontaneous-MVR, and AVT-MVR groups, respectively (p = 0.40 between LLV vs. Spontaneous-MVR groups and p = 0.83 between LLV vs. AVT-MVR groups). Multivariable analyses determined that HCC and decompensation risks in the LLV group were comparable to those with Spontaneous-MVR and AVT-MVR groups (all p >0.05). Propensity score matching also reproduced similar results for HCC and decompensation risks (all p>0.05 between LLV vs. Spontaneous-MVR groups and between LLV vs. AVT-MVR groups).

Conclusions:

Untreated LLV in HBV-infected compensated cirrhosis is not associated with increased risk of disease progression compared with Spontaneous-MVR and AVT-MVR. These data have important implications for practice and further research.
Scavenger receptor a is a major homeostatic regulator that restrains drug-induced liver injury
Authors: Guo Chunqing , Liu Wenjie , Liu Zheng , Cai Jinyang , Yu Xiaofei , Wang Hongxia , Li Xia , Zuo Daming , Jiang Xixian , Zhang Bei , Liu Jinze , Sanyal Arun J. , Puri Puneet , Zhou Huiping , Wang Xiang-Yang
Published: January 2023

Background and Aim:

Drug-induced liver injury occurs frequently and can be life threatening. Although drug-induced liver injury is mainly caused by the direct drug cytotoxicity, increasing evidence suggests that the interplay between hepatocytes and immune cells can define this pathogenic process. Here, we interrogate the role of the pattern recognition scavenger receptor A (SRA) for regulating hepatic inflammation and drug-induced liver injury.

Approach and Results:

Using acetaminophen (APAP) or halothane-induced liver injury models, we showed that SRA loss renders mice highly susceptible to drug hepatotoxicity, indicated by the increased mortality and liver pathology. Mechanistic studies revealed that APAP-induced liver injury exaggerated in the absence of SRA was associated with the decreased anti-inflammatory and prosurvival cytokine IL-10 concomitant with excessive hepatic inflammation. The similar correlation between SRA and IL-10 expression was also seen in human following APAP uptake. Bone marrow reconstitution and liposomal clodronate depletion studies established that the hepatoprotective activity of SRA mostly resized in the immune sentinel KCs. Furthermore, SRA-facilitated IL-10 production by KCs in response to injured hepatocytes mitigated activation of the Jun N-terminal kinase-mediated signaling pathway in hepatocytes. In addition, supplemental use of IL-10 with N-acetylcysteine, only approved treatment of APAP overdose, conferred mice improved protection from APAP-induced liver injury.

Conclusion:

We identify a novel hepatocyte-extrinsic pathway governed by the immune receptor SRA that maintains liver homeostasis upon drug insult. Giving that drug (ie, APAP) overdose is the leading cause of acute liver failure, targeting this hepatoprotective SRA-IL-10 axis may provide new opportunities to optimize the current management of drug-induced liver injury.
Checkpoint inhibitor hepatotoxicity: pathogenesis and management
Authors: Cunningham Morven , Gupta Rohit , Butler Marcus
Published: January 2023

Immunotherapy, including immune checkpoint inhibitor (ICI) therapy, has been a paradigm shift in cancer therapeutics, producing durable cancer responses across a range of primary malignancies. ICI drugs increase immune activity against tumor cells, but may also reduce immune tolerance to self-antigens, resulting in immune-mediated tissue damage. ICI-associated hepatotoxicity usually manifests as hepatocellular enzyme elevation and may occur in 2%–25% of ICI-treated patients. Although ICI-associated hepatotoxicity is clinically and pathologically distinct from idiopathic autoimmune hepatitis, our understanding of its pathogenesis continues to evolve. Pending greater understanding of the pathophysiology, mainstay of management remains through treatment with high-dose corticosteroids. This approach works for many patients, but up to 30% of patients with high-grade hepatotoxicity may not respond to corticosteroids alone. Furthermore, atypical cholestatic presentations are increasingly recognized, and rare cases of fulminant hepatitis due to ICI hepatotoxicity have been reported. Optimal management for these challenging patients remains uncertain. Herein, we review the current understanding of pathogenesis of ICI-associated toxicities, with a focus on hepatotoxicity. Based on the existing literature, we propose evolving management approaches to incorporate strategies to limit excess corticosteroid exposure, and address rare but important presentations of cholestatic hepatitis and fulminant liver failure. Finally, as ICI hepatotoxicity frequently occurs in the context of treatment for advanced malignancy, we review the impact of hepatotoxicity and its treatment on cancer outcomes, and the overall safety of re-challenge with ICI, for patients who may have limited treatment options.
Increasing gallstone disease prevalence and associations with gallbladder and biliary tract mortality in the US
Authors: Unalp-Arida Aynur , Ruhl Constance E.
Published: January 2023

Background and Aims:

We examined gallbladder and biliary tract mortality predictors in the US National Health and Nutrition Examination Survey (NHANES), 1988-1994, with 31 years of linked mortality data, and gallstone disease prevalence trends and associations in NHANES 2017-March 2020 prepandemic data.

Approach and Results:

In NHANES 1988-1994, 18,794 participants were passively followed for mortality, identified by death certificate underlying or contributing causes, by linkage to the National Death Index through 2019. In NHANES 2017-March 2020, gallstone disease history was ascertained from 9232 adults. During NHANES 1988-2019 follow-up (median, 23.3 y), 8580 deaths occurred from all causes and 72 deaths with gallbladder or biliary tract disease. In multivariable-adjusted analysis, older age, male sex, prediabetes or diabetes, and physical inactivity were associated with gallbladder and biliary tract mortality, and non-Hispanic Black and Mexican American race-ethnicity were inversely associated. Between 1988-1994 and 2017-March 2020, gallstone disease prevalence increased from 7.4% to 13.9% and gallbladder surgery from 6.0% to 11.6%. In 2017-March 2020 in multivariable-adjusted analysis, female sex, diabetes, liver disease, proton pump inhibitors, abdominal pain, increased age, BMI, and liver stiffness were associated with gallstone disease, and non-Hispanic Black and non-Hispanic Asian race and alcohol were inversely associated.

Conclusions:

In the US population, gallstone disease prevalence doubled over 3 decades, possibly because of the worsening of metabolic risk factors and growth of laparoscopic cholecystectomy. Gallbladder and biliary tract mortality and gallstone disease associations included factors such as prediabetes or diabetes, liver stiffness and proton pump inhibitors.
Mapping the hepatic immune landscape identifies monocytic macrophages as key drivers of steatohepatitis and cholangiopathy progression
Authors: Guillot Adrien , Winkler Marc , Silva Afonso Milessa , Aggarwal Abhishek , Lopez David , Berger Hilmar , Kohlhepp Marlene S. , Liu Hanyang , Özdirik Burcin , Eschrich Johannes , Ma Jing , Peiseler Moritz , Heymann Felix , Pendem Swetha , Mahadevan Sangeetha , Gao Bin , Diehl Lauri , Gupta Ruchi , Tacke Frank
Published: January 2023

Background and Aims:

The progression of chronic liver diseases towards liver cirrhosis is accompanied by drastic tissue changes. This study combines elaborate transcriptomic and histological methods aiming at spatially resolving the hepatic immune microenvironment in NAFLD (including NASH, primary sclerosing cholangitis, primary biliary cholangitis, and severe alcoholic hepatitis).

Approach and Results:

Human liver samples were subjected to RNA-sequencing (n=225) and imaging cytometry (n=99) across 3 independent patient cohorts. Liver samples from alcoholic hepatitis and primary biliary cholangitis patients were used for comparison. Myeloid populations were further characterized in corresponding mouse models. Imaging, clinical, and phenotypical data were combined for multidimensional analysis. NAFLD/NASH and primary sclerosing cholangitis disease stages were associated with loss of parenchymal areas, increased ductular cell accumulation, and infiltration of immune cells. NASH patients predominantly exhibited myeloid cell accumulation, whereas primary sclerosing cholangitis patients additionally had pronounced lymphoid cell responses. Correlating to disease stage, both etiologies displayed intense IBA1+CD16lowCD163low macrophage aggregation in nonparenchymal areas, with a distinct spatial proximity to ductular cells. Mouse models revealed that disease-associated IBA1+ hepatic macrophages originated from bone marrow–derived monocytes. Using an unbiased, machine learning–based algorithm, IBA1 in combination with hepatocyte and ductular cell immunostaining–predicted advanced cirrhosis in human NASH, primary sclerosing cholangitis, and alcoholic hepatitis.

Conclusions:

Loss of hepatocytes and increased ductular reaction are tightly associated with monocyte-derived macrophage accumulation and represent the most prominent common immunological feature revealing the progression of NAFLD, primary sclerosing cholangitis, primary biliary cholangitis, and alcoholic hepatitis, suggesting IBA1+CD163low macrophages are key pathogenic drivers of human liver disease progression across diverse etiologies.
Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management
Authors: Allaire Manon , Thabut Dominique
Published: January 2023

Background and Aims:

Portal hypertension (PHT) and HCC are 2 major complications of cirrhosis that often coexist in the same patient and impact the prognosis, especially in patients with acute variceal bleeding. In this review, we aim to discuss the best strategy for PHT screening and primary prophylaxis, as well as the management of acute variceal bleeding, to improve the management of PHT in HCC patients.

Results:

Recent therapeutic advances observed in the management of HCC, notably through the advent of immunotherapy, have led to a clear improvement in the survival of patients. The prevention of complications related to underlying cirrhosis, such as PHT and acute variceal bleeding, is now part of the management of HCC patients. The Baveno VII conference recently redefined screening and prophylaxis in patients with cirrhosis. However, data regarding the applicability of these criteria in patients with HCC have been sparse. From our point of view, the Baveno criteria are not appropriate to exclude high-risk esophageal varices (EV) in HCC patients, and endoscopy should be performed except in HCC patients with a liver stiffness measurement (LSM) ≥25 kPa, who should benefit from nonselective beta-blockers (NSSBs) without performing endoscopy. We are also in favor of using NSBBs as primary prophylaxis in patients with EV regardless of the size and with gastric varices since these patients display clinically significant PHT.

Conclusions:

Appropriate evaluation and treatment of PHT remain major issues in improving the outcomes of HCC patients. Many questions remain unanswered, opening the field to many areas of research.
Benefit of treatment based on indapamide mostly combined with perindopril on mortality and cardiovascular outcomes: a pooled analysis of four trials
Authors: Chalmers John , Mourad Jean-Jacques , Brzozowska-Villatte Romualda , De Champvallins Martine , Mancia Giuseppe
Published: January 2023

Objective:

The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs).

Method:

Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment.

Results:

The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity (I
2 = 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (−15%), cardiovascular death (−21%), fatal stroke (−36%) and all strokes (−27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%).

Conclusion:

Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.
Safety and Efficacy of Resident-Performed Gonioscopy-Assisted Transluminal Trabeculotomy
Authors: Patterson Ian , Avdagic Ema , Qiu Mary
Published: January 2023

Précis:

GATT can be performed efficaciously and safely by PGY-3 and PGY-4 residents, with clinical outcomes and complication rates that mirror those of attending-performed GATT cohorts from the literature.

Purpose:

Report outcomes of gonioscopy-assisted transluminal trabeculotomy (GATT) performed by PGY-3 and PGY-4 residents.

Methods:

A retrospective chart review was performed for patients undergoing resident-performed GATT. Eyes with previous traditional glaucoma surgery (trabeculectomy or aqueous shunt) or neovascular glaucoma were excluded from this analysis. The primary aim was to assess whether resident-performed GATTs demonstrated success rates comparable with the GATT literature. Surgical success was defined as intraocular pressure (IOP)<21 mmHg, and an IOP reduction of 20% from baseline, and no subsequent IOP-lowering surgery. The secondary and tertiary aims were to describe complication rates and operating times for resident-performed GATTs, respectively.

Results:

A total of 50 eyes from 40 patients with various types of glaucoma were included. Eyes either underwent resident-performed GATT-alone (N=9) or GATT+cataract extraction with intraocular lens implantation (CEIOL) (N=41). The surgical success rate at 6 months was 71% for GATT-alone and 42% for GATT+CEIOL. Three eyes required subsequent IOP-lowering surgery. The hyphema rate was 16% at postoperative week 1 and 6% at postoperative month 1. The IOP spike (>30 mmHg) rate was 18%. Mean surgical time for both GATT-alone and GATT+CEIOL was longer for PGY-4s than for PGY-3s, attributable to less attending assistance during PGY-4 cases and more resident-performed cataracts in PGY-4 GATT+CEIOL cases (85%) compared with PGY-3 cases (35%).

Conclusions:

GATT can be performed efficaciously and safely by PGY-3 and PGY-4 residents, with clinical outcomes and complication rates that mirror those of attending-performed GATT cohorts from the literature.
miR-1306-3p directly activates P2X3 receptors in primary sensory neurons to induce visceral pain in rats
Authors: Wu Yan-Yan , Wang Qian , Zhang Ping-An , Zhu Cheng , Xu Guang-Yin
Published: January 2023

Mounting evidence indicates that microRNAs (miRNAs) play critical roles in various pathophysiological conditions and diseases, but the physiological roles of extracellular miRNAs on the disease-related ion channels remain largely unknown. Here, we showed that miR-1306-3p evoked action potentials and induced inward currents of the acutely isolated rat dorsal root ganglion (DRG) neurons. The miR-1306-3p–induced effects were significantly inhibited by A317491, a potent inhibitor of the P2X3 receptor (P2X3R), or disappeared after the knockdown of P2X3Rs in DRG neurons. We further identified R180, K315, and R52 as the miR-1306-3p interaction sites on the extracellular domain of P2X3Rs, which were distinct from the orthosteric ATP-binding sites. Intrathecal injection of miR-1306-3p produced visceral pain but not somatic pain in normal control rats. Conversely, intrathecal application of a miR-1306-3p antagomir and A317491 significantly alleviated visceral pain in a rat model of chronic visceral pain. Together, our findings suggest that miR-1306-3p might function as an endogenous ligand to activate P2X3Rs, eventually leading to chronic visceral pain.
Impact of Transfusing Packed Red Blood Cells Through a Rapid Infuser on Potassium Levels
Authors: Metcalf Ashley , Kitchens Debra , Reddic John , Liao Wesley , Whitcomb John , Wallenborn Grace , Cull John
Published: January 2023

Background:

Hyperkalemia is associated with the rapid transfusion of packed red blood cells in trauma patients. Rapid infusers can infuse blood up to 500 ml/min.

Objective:

This study aimed to determine whether infusing packed red blood cells through a rapid infuser impacts the potassium levels of the infused blood.

Methods:

Two baseline samples were obtained to measure potassium and hemolysis scores in 12 units of expired blood prior to infusion. The blood was then infused via the Belmont Rapid Infuser into collection bags at varying infusion rates (50, 100, 250, and 500 ml/min) utilizing different gauge catheter sizes (18-gauge, 16-gauge, and Cordis catheter). Two postinfusion blood samples were collected and tested for potassium and hemolysis scores and compared with preinfusion values. This process was then repeated with fresh blood.

Results:

The potassium levels of the samples taken from each unit prior to infusion (average difference 0.245) and after infusion (average difference 0.08) correlated well. There was no difference in potassium levels pre- and postinfusion at any infusion rate after accounting for catheter size and age of blood. The median potassium level of the fresh blood was 5.025 prior to infusion and 4.875 after infusion. The median potassium level of the expired blood was 16.05 prior to infusion and 16.4 postinfusion. There was no significant difference in the hemolysis scores between the preinfusion and postinfusion samples.

Conclusions:

Hyperkalemia in trauma patients undergoing massive transfusions is not a result of mechanical hemolysis from the high rates of blood infusion.
Outcomes in liver transplant recipients with nonalcoholic fatty liver disease-related HCC: results from the US multicenter HCC transplant consortium
Authors: Verna Elizabeth C. , Phipps Meaghan M. , Halazun Karim J. , Markovic Daniela , Florman Sander S. , Haydel Brandy M. , Ruiz Richard , Klintmalm Goran , Lee David D. , Taner Burcin , Hoteit Maarouf A. , Tevar Amit D. , Humar Abhinav , Chapman William C. , Vachharajani Neeta , Aucejo Federico N. , Melcher Marc L. , Nguyen Mindie H. , Nydam Trevor L. , Markmann James F. , Mobley Constance , Ghobrial Rafik M. , Langnas Alan N. , Carol Carney  , Berumen Jennifer , Schnickel Gabriel T. , Sudan Debra , Hong Johnny C. , Rana Abbas , Jones Christopher M. , Fishbein Thomas M. , Busuttil Ronald W. , Agopian Vatche ,   The US Multicenter HCC Transplant Consortium
Published: January 2023

NAFLD will soon be the most common indication for liver transplantation (LT). In NAFLD, HCC may occur at earlier stages of fibrosis and present with more advanced tumor stage, raising concern for aggressive disease. Thus, adult LT recipients with HCC from 20 US centers transplanted between 2002 and 2013 were analyzed to determine whether NAFLD impacts recurrence-free post-LT survival. Five hundred and thirty-eight (10.8%) of 4981 total patients had NAFLD. Patients with NAFLD were significantly older (63 vs. 58, p<0.001), had higher body mass index (30.5 vs. 27.4, p<0.001), and were more likely to have diabetes (57.3% vs. 28.8%, p<0.001). Patients with NAFLD were less likely to receive pre-LT locoregional therapy (63.6% vs. 72.9%, p<0.001), had higher median lab MELD (15 vs. 13, p<0.001) and neutrophil-lymphocyte ratio (3.8 vs. 2.9, p<0.001), and were more likely to have their maximum pre-LT alpha fetoprotein at time of LT (44.1% vs. 36.1%, p<0.001). NAFLD patients were more likely to have an incidental HCC on explant (19.4% vs. 10.4%, p<0.001); however, explant characteristics including tumor differentiation and vascular invasion were not different between groups. Comparing NAFLD and non-NAFLD patients, the 1, 3, and 5-year cumulative incidence of recurrence (3.1%, 9.1%, 11.5% vs. 4.9%, 10.1%, 12.6%, p=0.36) and recurrence-free survival rates (87%, 76%, and 67% vs. 87%, 75%, and 67%, p=0.97) were not different. In competing risks analysis, NAFLD did not significantly impact recurrence in univariable (HR: 0.88, p=0.36) nor in adjusted analysis (HR: 0.91, p=0.49). With NAFLD among the most common causes of HCC and poised to become the leading indication for LT, a better understanding of disease-specific models to predict recurrence is needed. In this NAFLD cohort, incidental HCCs were common, raising concerns about early detection. However, despite less locoregional therapy and high neutrophil-lymphocyte ratio, explant tumor characteristics and post-transplant recurrence-free survival were not different compared to non-NAFLD patients.
Management of gestational weight gain in obese or overweight women based on resting energy expenditure: A pilot cohort study
Authors: Zhao Xiuling , Wen Shi Wu , Ma Wei , Xu Pili , Zhang Chunmei , Jiang Shan , Gaudet Laura M. , Gao Jie
Published: January 2023

Resting energy expenditure (REE) comprises 60% of total energy expenditure and variations may be associated with gestational weight gain (GWG). This study aims to explore the usability and feasibility of REE guided intervention for GWG in obese and overweight women. We conducted a prospective cohort study in LuHe Hospital of Capital Medical University in Beijing, China between May 1, 2017 and May 31, 2018. Obese/overweight women who had routine prenatal care visit at 10 to 13 weeks of gestation, were recruited after written informed consent was obtained. The intervention group (those women who were recruited between January 1 and May 31, 2018) used REE calculated daily total energy to manage GWG, while the control group (those women who were recruited between May 1 and December 31, 2017) used prepregnancy body mass index calculated daily total energy to manage GWG. GWG and daily total energy between the 2 groups were recorded from 10 to 13 weeks of gestation to delivery. A total of 68 eligible women (35 in intervention group and 33 in control group) were included in the final analysis. Daily total energy in the intervention group increased less than the control group, especially from 2nd trimester to 3rd trimester (1929.54 kcal/d vs. 2138.33 kcal/d). The variation of daily total energy from 1st trimester to 3rd trimester in the intervention group was lower than the control group (226.17 kcal/d vs 439.44 kcal/d). Overall GWG of the intervention group (13.45 kg) was significantly lower than the control group (18.20 kg). The percentage of excess-GWG in the intervention group (31.42%) was also significantly lower than the control (57.57%). Findings from our pilot study suggest that diet recommendation basting on REE may improve management of GWG in obese/overweight women.
Comparative analysis of potentially inappropriate medication use in long-term care facility residents and community-dwelling elders: A matched cohort study
Authors: Lee Yumin , Jang Suhyun , Kang Hee-Jin , Jang Sunmee
Published: January 2023

As the population of the elderly in long-term care facilities has grown, the number of users of potentially inappropriate medication (PIM) is also increasing. With this study, we aimed to investigate the pattern of PIM usage and related factors among the elderly receiving long-term care services. Using the South Korean National Health Insurance Service Elderly Cohort Database, we conducted a retrospective matched cohort study. Elderly residents (n = 1980) in long-term care facilities in 2013 were selected and matched 1:1 with elderly persons living in the community applying propensity score method. The matching variables were sex, age, health insurance type, long-term care grade, Charlson’s Comorbidity Index score, presence of dementia, cerebrovascular disease, or Parkinson’s disease, and number of drugs prescribed. PIM use was assessed according to Beers criteria 2019. The prevalence of PIM was found to be higher among the elderly in long-term care facilities (86.77%) than among community-dwelling individuals (75.35%). Logistic regression showed that long-term care facility residents were 1.84 odds more likely to use PIM than community-dwelling older adults. We also confirmed that the average number of medications taken per day and the number of outpatient visits were the major influencing factors affecting PIM prescriptions. In addition, elders living in long-term care facilities were prescribed more PIM drugs acting on the central nervous system than community-dwelling older adults. The results of this study show that among those receiving long-term care services, older people in long-term care facilities use PIM more than do the elderly living at home. Medication management programs need to be developed to reduce the use of PIM in long-term care facilities.
Prediction of fluid responsiveness by dynamic preload parameters in children undergoing thoracoscopic surgery with one-lung ventilation – A prospective observational study
Authors: Xie Siyuan , Han Ding , Chen Gang , Pan Shoudong
Published: January 2023

Optimal perioperative fluid management is essential for reducing complications in children undergoing thoracoscopic surgery. The study aimed to assess the performance of 2 dynamic preload parameters – pulse pressure variation (PPV) and stroke volume variation (SVV)- either used alone or combined into a multivariable regression model for predicting fluid responsiveness in children undergoing video-assisted thoracoscopic surgery with one-lung ventilation. Children aged 1 to 6 years old undergoing video-assisted pulmonary segmentectomy or lobectomy were enrolled. Volume loading with 5 mL/kg of hydroxyethyl starch was administered over 15 minutes after establishment of artificial pneumothorax. PPV, SVV, cardiac index, cardiac cycle efficiency, and the difference between systolic blood pressure and dicrotic pressure were recorded using the pressure recording analytical method before and after volume loading. Patients with an elevation in cardiac index greater than 10% were defined as responders, and the remaining patients were nonresponders. Of 40 children, 36 were included in the final analysis, containing 13 responders and 23 nonresponders. SVV had an accuracy of 74% (95% confidence interval, 55–93%) for predicting fluid responsiveness, and a best cutoff of 22% showed a sensitivity of 62% and a specificity of 96%. PPV was incapable of discriminating responders from nonresponders. The multivariate regression model did not perform better than SVV alone. We found PPV failed to predict fluid responsiveness, while SVV predicted fluid responsiveness reasonably in the present context. There was no enhancement in predictivity accuracy with multivariable regression models. The accuracy of these approaches was limited, and more discriminative methods need to be found.
Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis: A case report and literature review
Authors: Fu Ji-Xin , Wang Xu-Jie , Xia Min , Wang Xin-Jian
Published: January 2023

Rationale:

Lung cancer (LC) is a malignant tumor with the highest morbidity and mortality in the world. The most common metastatic sites of LC are the brain (47%), bone (36%), liver (22%), adrenal glands (15%), thoracic cavity (11%) and distant lymph nodes (10%). Peritoneal carcinomatosis (PC) is a rare clinical event in LC patients. Considering the rarity and nonspecific clinical symptoms of peritoneal metastasis among LC patients, a case of peritoneal metastasis secondary to LC incidentally observed by laparoscopic appendectomy is unusual.

Patient concerns:

Here, we present a 53-year-old never-smoker woman who presented to the emergency department with a 2-day history of pain in the right abdominal quadrant. Later, laparoscopy revealed acute suppurative appendicitis accompanied by a peritoneal metastatic mass.

Diagnosis:

The patient was diagnosed with PC secondary to metastatic LC complicated with acute suppurative appendicitis by immunohistochemistry. Positron emission tomography computed tomography (PET CT) findings further strengthen the evidence of PC from LC.

Outcomes:

Based on the results of genomic analysis, the patient received targeted therapy with osimertinib 80 mg/d.

Lessons:

Due to the discovery of new targets, the use of molecular therapies improved progression-free survival (PFS) and overall survival (OS), which increases the chance of identifying peritoneal metastasis of LC. For LC patients with abdominal symptoms, clinicians should be aware of the possibility of peritoneal metastasis from LC, especially for patients diagnosed with lung adenocarcinoma or with pleural effusion.
Robot-assisted anterior transpedicular screw fixation with 3D printed implant for multiple cervical fractures: A case report
Authors: Pei Lei , Yuan Wei , Liu Xinchun , Cong Lin , Zhu Yue
Published: January 2023

Rationale:

The anterior transpedicular screw (ATPS) fixation in the cervical spine provides the advantages of both anterior and posterior cervical surgery; however, it poses a high risk of screw insertion. In addition, a 3D printed implant can match ATPS fixation and reconstruction of the vertebral body. Robot-assisted surgery can make this process easier and potentially improve the safety and accuracy of the procedure.

Patient concerns:

A 64-year-old female was hit by a heavy object 4 days before presentation to our hospital. The patient exhibited a muscle strength of 0/5 in both the lower limbs and 3/5 in both the upper limbs. The visual analogue scale (VAS) for the neck was 5 points. Computed tomography (CT) of the cervical spine identified a burst fracture of the C5 vertebral body, and longitudinal splitting fracture of the C6 and C7 vertebral bodies accompanied with a split in the lamina. Magnetic resonance imaging (MRI) revealed a spinal cord edema from the C3 to the C7 level.

Diagnosis:

Multiple cervical fractures with spinal cord injury.

Interventions:

Anterior C4-5 and C5-6 disc resection, C5 corpectomy, robot-assisted ATPS fixation with the 3-D printed implant was performed.

Outcomes:

The CT scans revealed a satisfactory location of the internal implantation without any signs of complications associated with implantations. Six months later, the muscle strength of both the upper limbs increased from level 3 to level 5, VAS of neck decreased from 5 to 0.

Lessons:

Robot-assisted ATPS internal fixation combined with custom implantation surgery using a 3D printed vertebral body provides an important solution to solve special cases.
The comprehensive comparison of imaging sign from CT angiography and noncontrast CT for predicting intracranial hemorrhage expansion: A comparative study
Authors: Chung Gyung Ho , Goo Ja Hong , Kwak Hyo Sung , Hwang Seung Bae
Published: January 2023

Expansion of intracranial hemorrhage (ICH) is an important predictor of poor clinical outcomes. Various imaging markers on non-contrast computed tomography (NCCT) or computed tomographic angiography (CTA) have been reported as predictors of ICH expansion. We aimed to compare the associations between various CT imaging markers and ICH expansion. Patients with spontaneous ICH who underwent initial NCCT, CTA, and subsequent NCCT between January 2016 and December 2019 were retrospectively identified. ICH expansion was defined as a volume increase of > 33% or > 6 mL. We analyzed the presence of imaging markers such as the black hole sign, blend sign, island sign, or swirl sign on initial NCCT or spot sign on CTA. An alternative free-response receiver operating characteristic curve analysis was performed using a 4-point scoring system based on the consensus of the reviewers. The predictive value of each marker was assessed using univariate and multivariate logistic regression analyses. A total of 250 patients, including 60 (24.0%) with ICH expansion, qualified for the analysis. Among the patients with spontaneous ICH, 118 (47.2%) presented with a black hole sign, 52 (20.8%) with a blend sign, 93 (37.2%) with an island sign, 79 (31.6%) with a swirl sign, and 56 (22.4%) with a spot sign. In univariate logistic regression, the initial ICH volume (P = .038), initial intraventricular hemorrhage (IVH) presence (P < .001), swirl sign (P < .001), and spot sign (P < .001) were associated with ICH expansion. Multivariate analysis confirmed that the presence of initial IVH (odds ratio, 4.111; P = .002) and spot sign (odds ratio, 109.5; P < .001) were independent predictors of ICH expansion. Initial ICH volume, IVH, swirl sign, and spot sign are associated with ICH expansion. The presence of spot signs and IVH were independent predictors of ICH expansion.
Non-pharmacological therapies for treating chronic pelvic pain in women: A review
Authors: Wang Xinlu , Ding Ning , Sun Yuanjie , Chen Yu , Shi Hangyu , Zhu Lili , Gao Shuai , Liu Zhishun
Published: January 2023

Chronic pelvic pain (CPP) is an intricate condition with multiple etiologies that lead to indefinite pain mechanisms. Physicians and researchers are challenged in its treatment, and the combined therapy of pharmacologic and non-pharmacologic treatment has been recognized as a multidisciplinary approach cited by guidelines and adopted in clinical practice. As an alternative therapy for CPP, non-pharmacologic therapies benefit patients and deserve further study. This study reviews the literature published from January 1991 to April 2022 on non-pharmacologic therapies for CPP in adult women. Based on a survey, this review found that the most commonly used non-pharmacological therapies for CPP include pelvic floor physical therapy, psychotherapy, acupuncture, neuromodulation, and dietary therapy. By evaluating the efficacy and safety of each therapy, this study concluded that non-pharmacological therapies should be included in the initial treatment plan because of their high degree of safety and low rate of side effects. To fill the lack of data on non-pharmacologic therapies for CPP, this study provides evidence that may guide treatment and pain management.
Effectiveness and safety of different academic schools of traditional Chinese medicine in the treatment of obesity: A protocol for systematic review and meta-analysis
Authors: Gang Xiaochao , Gao Tianjiao , Han Yiran , Tai Yuxing , Zhong Chongwen , Chen Shaotao , Gao Ying , Li Lijie , Xiao Zhenxiang , Barat Dilnur , Liu Mingjun
Published: January 2023

Background:

Obesity is a global epidemic. Since 1975, the global obesity rate has almost tripled. Although many systematic reviews and clinical trials have shown that traditional Chinese medicine (TCM) can effectively treat obesity, the effectiveness and safety of different academic schools of TCM in treating obesity have not been systematically evaluated.

Methods:

The retrieval language of this study was Chinese and English. From the date of creation of the following data to June 2023, the data of Medline, PubMed, Embase, Cochrane Science Network, China Biomedical Literature Database, Central Controlled Trial Registration Center, and China Science Journal Database were retrieved, respectively. This study included clinical randomized controlled trials related to the treatment of obesity by different academic schools of TCM. The main outcome measures were body mass index, waist circumference, hip circumference, waist hip ratio, body fat content, fasting blood glucose, glycosylated hemoglobin, and blood lipid level. In addition, we manually searched other resources, including reference lists of identified publications, conference articles, and gray literature.

Results:

This study will provide a more diverse choice of treatment options.

Conclusion:

The purpose of this study is to summarize and evaluate the effectiveness and safety of different academic schools of TCM in improving and treating obese patients from clinical trials, so as to provide more options for obesity treatment.
Expression of LINE-1 retrotransposon in early human spontaneous abortion tissues
Authors: Lou Chao , Qiang Rong , Wu Hanzhi , Zhang Liping , Li Wei , Jia Ting , Liu Xing
Published: January 2023

Background:

The aim of this study is to investigate a new mechanism that may affect spontaneous abortions (SA): Can long interspersed nuclear element-1 (LINE-1) insertions in embryo cells lead to early SA?

Methods:

The method involves prospective study on new mechanism of human early SA. Twenty SA tissues and 10 induced abortion (IA) tissues were utilized for this experiment. Western Blot, Immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction were used to analyze different LINE-1 proteins and mRNA expression between early SA tissues and early IA tissues. SPSS software version 21.0 was used for statistical analysis.

Results:

Western Blot demonstrated that the LINE-1 protein expression in SA tissues (Mean: 60.2%) is higher than in IA tissues (Mean: 30.3%) in 91% of the compared samples. reverse transcription-polymerase chain reaction showed that LINE-1 mRNA expression in SA tissues (Mean: 64.2%) is higher than in IA tissues (Mean: 29.2%) in 6 primer pairs in 89% of the compared samples. IHC showed that the LINE-1 protein expression in SA tissues (Mean: 59.2%) is higher than in IA tissues (Mean: 28.8%) in 83% of the compared samples.

Conclusions:

Expression of LINE-1 in early SA tissues is higher than in IA tissues, LINE-1 may lead to early SA and LINE-1 plays a role in early SA, this shows that a new mechanism may be involved in SA.
Variables associated with concordance or discordance for delirium diagnosis between referring and consulting physicians at a Tertiary Hospital in Colombia: Prospective observational study
Authors: Zapata Carolina , Garces Juan J. , Duica Kelly , Restrepo Cristóbal , Ocampo María V. , Velásquez-Tirado Juan D. , Ricardo Carmenza , Trzepacz Paula T. , Franco José G.
Published: January 2023

Delirium is an acute state of impaired consciousness and a medical urgency. Its broad range of alterations in mental status make diagnosis challenging. Awareness and accurate provisional diagnosis by nonpsychiatric clinicians are important for prompt management. Because delirium symptoms overlap and mimic other neuropsychiatric conditions, a referral to a consultant psychiatrist is often needed. The aim of this study was to determine the discriminating variables that are associated with concordance or discordance for a DSM-5 delirium diagnosis made by the consultation/liaison (C/L) psychiatrist as compared to the referral diagnosis/reasons given by the referring physicians for inpatients from a Tertiary Hospital in a Latin-American country. Prospective study of a cohort of 399 consecutive patients admitted to any ward of a university hospital in Medellin-Colombia and referred by a specialist physician to the C/L Psychiatry service. Analyses for diagnostic concordance used a nested sample of 140 cases diagnosed with delirium by the psychiatrist. Two multivariate logistic models were run, for delirium diagnosis concordance and discordance between the referring physician and C/L psychiatrist. The referral diagnosis was concordant with that of Psychiatry in 90/140 patients in 64.3%, with 35.7% discordance. Increasing age (OR = 1.024) and internal medicine ward (OR = 3.0) were significantly related (Wald statistic P < .05) to concordance in the multivariate analysis whose model accuracy was 68.6%. Trauma/orthopedics ward (OR = 5.7) and SARS-CoV-2 infection (OR = 3.8) were important contributors to the model fit though not significant. Accuracy of the discordance model was 70.7%, where central nervous system (CNS) disorder (OR = 6.1) and referrals from ICU (OR = 4.9), surgery (OR = 4.6), neurology/neurosurgery (OR = 5.1) and another consultant (OR = 4.7) were significantly related (Wald statistic P < .05), while metabolic/endocrine disorder (OR = 2.7) was important for model fit, but not significant. Concordance for delirium diagnosis was higher from services where education, guidelines and working relationships with C/L Psychiatry could have contributed beneficially whereas, surprisingly, CNS disorders and neurology/neurosurgery services had higher discordance, as well as the ICU. Routine use of brief sensitive delirium assessment tools such as the DDT-Pro could enhance provisional delirium diagnosis.
Bioinformatics and systems biology approaches to identify the effects of COVID-19 on neurodegenerative diseases: A review
Authors: Bu Fan , Guan Ruiqian , Wang Wanyu , Liu Zhao , Yin Shijie , Zhao Yonghou , Chai Jianbo
Published: January 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease (COVID-19), has been devastated by COVID-19 in an increasing number of countries and health care systems around the world since its announcement of a global pandemic on 11 March 2020. During the pandemic, emerging novel viral mutant variants have caused multiple outbreaks of COVID-19 around the world and are prone to genetic evolution, causing serious damage to human health. As confirmed cases of COVID-19 spread rapidly, there is evidence that SARS-CoV-2 infection involves the central nervous system (CNS) and peripheral nervous system (PNS), directly or indirectly damaging neurons and further leading to neurodegenerative diseases (ND), but the molecular mechanisms of ND and CVOID-19 are unknown. We employed transcriptomic profiling to detect several major diseases of ND: Alzheimer 's disease (AD), Parkinson' s disease (PD), and multiple sclerosis (MS) common pathways and molecular biomarkers in association with COVID-19, helping to understand the link between ND and COVID-19. There were 14, 30 and 19 differentially expressed genes (DEGs) between COVID-19 and Alzheimer 's disease (AD), Parkinson' s disease (PD) and multiple sclerosis (MS), respectively; enrichment analysis showed that MAPK, IL-17, PI3K-Akt and other signaling pathways were significantly expressed; the hub genes (HGs) of DEGs between ND and COVID-19 were CRH, SST, TAC1, SLC32A1, GAD2, GAD1, VIP and SYP. Analysis of transcriptome data suggests multiple co-morbid mechanisms between COVID-19 and AD, PD, and MS, providing new ideas and therapeutic strategies for clinical prevention and treatment of COVID-19 and ND.