Efficacy and safety of herbal medicine combined with acupuncture in pediatric epilepsy treatment: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of herbal medicine and acupuncture combination for pediatric epilepsy treatment. METHODS: Databases were searched from their interception until October 2023 to identify randomized controlled trials focusing on the therapeutic efficacy of herbal medicine-acupuncture combination (intervention group) for pediatric epilepsy. The primary outcome was the risk of treatment failure, whereas the secondary outcomes included the risk of post-treatment electroencephalogram (EEG) abnormalities and adverse events. Subgroup analyses were conducted based on the type of herbal compound formulas. Meta-regression analysis was conducted to examine the influence of patient demographics and clinical history on the therapeutic efficacy of herbal medicine-acupuncture combination for pediatric epilepsy. To assess the cumulative evidence, trial sequential analysis (TSA) was performed. RESULTS: The analysis included 10 trials involving a total of 882 pediatric patients. Meta-analysis revealed that the intervention group had a lower risk of treatment failure than the control group (risk ratio [RR] = 0.3, 95% confidence interval [CI]: 0.19-0.47, P<0.00001, I2 = 0%, 10 trials). Subgroup analyses showed that therapeutic efficacy was consistent among the different herbal compound formulas. Meta-regression analysis revealed that the efficacy of the treatments did not significantly vary with patient age, male sex, and duration of seizure history. TSA suggested that herbal medicine-acupuncture combination exerted a robust and conclusive effect on seizure treatment. Although the combined used of herbal medicine and acupuncture was not associated with a lower risk of post-treatment EEG abnormalities (RR = 0.82, 95%CI:0.6-1.11, P = 0.2, 3 trials), the risk of adverse events was reduced (RR = 0.27, 95%CI:0.18-0.41, P<0.00001, 4 trials). CONCLUSION: The meta-analysis suggested that combined use of herbal medicine and acupuncture is a promising and safe clinical approach for pediatric epilepsy treatment. Further large-scale studies are necessary to conclusively determine the efficacy and safety of herbal medicine and acupuncture in pediatric epilepsy treatment.

Impact of the geriatric nutritional risk index on long-term outcomes in patients undergoing hemodialysis: a meta-analysis of observational studies.

Background: This meta-analysis aimed to synthesize current evidence on the association between the Geriatric Nutritional Risk Index (GNRI) and long-term outcomes in patients undergoing hemodialysis. Methods: Electronic databases were systematically searched for relevant studies that investigated the association between GNRI and long-term outcomes in hemodialysis patients until November 2023. The primary outcome was the association between the GNRI (i.e., low versus high) and overall mortality risk, while the secondary outcome was the relationship between the GNRI and cardiovascular mortality risk. Results: Thirty cohort studies involving 55,864 patients were included. A low GNRI was found to be significantly associated with increased overall mortality (hazard ratio [HR]: 2.42, 95% confidence interval [CIs]: 2.10-2.79, p < 0.00001, I2 = 65%). Each unit increase in GNRI corresponded to a 5% reduction in mortality risk (HR: 0.95, 95% CI: 0.93-0.96, p < 0.00001, I2 = 79%). The association remained consistent across Asian (HR = 2.45, 95% CI: 2.08-2.88, p < 0.00001, I2 = 70%) and non-Asian subgroups (HR = 2.3, 95% CI: 1.72-3.06, p < 0.00001, I2 = 23%). Meta-regression analysis of patient age (coefficient: -0.002; p = 0.896), male proportion (coefficient: 0.002; p = 0.875), percentage of diabetes mellitus (coefficient: -0.003; p = 0.605), and follow-up duration (coefficient: -0.003; p = 0.431) revealed that these moderator variables did not significantly influence the association between GNRI and overall mortality risk. Cardiovascular mortality risk also increased with low GNRI (HR, 1.93; 95%CI: 1.51-2.45, p < 0.00001; I2 = 2%). Similarly, an inverse association was observed between the GNRI values and cardiovascular mortality risk (HR, 0.94; 95% CI: 0.91-0.97; p < 0.0001; I2 = 65%) (per unit increase). Conclusion: The GNRI is a simple nutritional screening tool that can be used to effectively stratify patients undergoing hemodialysis globally. Further studies are warranted to determine whether nutrition optimization based on the GNRI improves long-term outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, CRD42023483729.

Adrenal insufficiency following cerebellar intracranial hemorrhage: a case report.

This report presents a case of a previously healthy 58 years-old man who had suffered from persistent weakness and dizziness after a cerebellar intracranial hemorrhage (ICH). Endocrine function tests revealed low levels of plasma cortisol (3.05 µg/dL; normal range: 5-25 µg/dL) and adrenocorticotropic hormone (ACTH) (6.0 pg/mL; normal range: 10-60 pg/mL). The subsequent ACTH stimulation test suggested partial or recent hypopituitarism, resulting in adrenal gland atrophy and a subnormal cortisol response. Ultimately, the dizziness was found to be caused by undiagnosed adrenal insufficiency, which was detected when a hypotensive fainting incident occurred during rehabilitation. The symptoms improved significantly with oral prednisone supplementation. Notably, the duration of impaired hypothalamic-pituitary-adrenal axis may last as long as a year. This case highlights that adrenal insufficiency can easily be overlooked since its symptoms are similar to those commonly seen with cerebellar stroke alone. Physicians must be aware of the symptoms of adrenal insufficiency in patients with brain insults and conduct the appropriate endocrine tests to clarify the underlying comorbidity.

Association between systemic sclerosis and risk of cerebrovascular and cardiovascular disease: a meta-analysis.

We aimed to evaluate the association between systemic sclerosis (SSc) and major cerebrovascular/cardiovascular risks through a systematic approach. Databases were systematically searched from their inception to October 10, 2023 for studies comparing cerebrovascular/cardiovascular event rates between patients with SSc and controls. The primary outcome was the stroke risk in patients with SSc. Secondary outcomes included risk of myocardial infarction (MI), cardiovascular disease (CVD), peripheral vascular disease (PVD), and venous thromboembolism (VTE). Seventeen studies with 6,642,297 participants were included. SSc was associated with a significantly increased risk of stroke (HR, 1.64; 95% confidence interval [CI], 1.35-2.01), CVD (HR, 2.12; 95% CI, 1.36-3.3), MI (HR, 2.15; 95% CI, 1.23-3.77), VTE (HR, 2.75; 95% CI, 1.77-4.28), and PVD (HR, 5.23; 95% CI, 4.25-6.45). Subgroup analysis revealed a significantly increased stroke risk in the non-Asian group (HR, 1.55; 95% CI, 1.26-1.9), while the Asian group displayed a higher but not statistically significant risk (HR, 1.86; 95% CI, 0.97-3.55). The study found that SSc is associated with a significantly increased risk of cerebrovascular/cardiovascular events. These findings highlight the importance of vasculopathy in SSc and suggest the need for enhanced clinical monitoring and preventive measures in this high-risk population.

Identification and characterization of a novel CASR mutation causing familial hypocalciuric hypercalcemia.

Context: Although a monoallelic mutation in the calcium-sensing receptor (CASR) gene causes familial hypocalciuric hypercalcemia (FHH), the functional characterization of the identified CASR mutation linked to the clinical response to calcimimetics therapy is still limited. Objective: A 45-year-old male presenting with moderate hypercalcemia, hypocalciuria, and inappropriately high parathyroid hormone (PTH) had a good response to cinacalcet (total serum calcium (Ca2+) from 12.5 to 10.1 mg/dl). We identified the genetic mutation and characterized the functional and pathophysiological mechanisms, and then linked the mutation to calcimimetics treatment in vitro. Design: Sanger sequencing of the CASR, GNA11, and AP2S1 genes was performed in his family. The simulation model was used to predict the function of the identified mutant. In vitro studies, including immunoblotting, immunofluorescence, a cycloheximide chase study, Calbryte™ 520 Ca2+ detection, and half-maximal effective concentration (EC50), were examined. Results: This proband was found to carry a de novo heterozygous missense I554N in the cysteine-rich domain of CASR, which was pathogenic based on the different software prediction models and ACGME criteria. The simulation model showed that CASR I554N mutation decreased its binding energy with Ca2+. Human CASR I554N mutation attenuated the stability of CASR protein, reduced the expression of p-ERK 1/2, and blunted the intracellular Ca2+ response to gradient extracellular Ca2+ (eCa2+) concentration. The EC50 study also demonstrated the correctable effect of calcimimetics on the function of the CASR I554N mutation. Conclusion: This novel CASR I554N mutation causing FHH attenuates CASR stability, its binding affinity with Ca2+, and the response to eCa2+ corrected by therapeutic calcimimetics.

Impact of intravenous dexmedetomidine on postoperative gastrointestinal function recovery: an updated meta-analysis.

BACKGROUND: Postoperative ileus (POI) is a complication that may occur after abdominal or nonabdominal surgery. Intravenous dexmedetomidine (Dex) has been reported to accelerate postoperative gastrointestinal function recovery; however, updated evidence is required to confirm its robustness. METHODS: To identify randomized controlled trials examining the effects of perioperative intravenous Dex on gastrointestinal function recovery in patients undergoing noncardiac surgery, databases including MEDLINE, EMBASE, Google Scholar, and Cochrane Library were searched on August 2023. The primary outcome was time to first flatus. Secondary outcomes included time to oral intake and defecation as well as postoperative pain scores, postoperative nausea/vomiting (PONV), risk of hemodynamic instability, and length of hospital stay (LOS). To confirm its robustness, subgroup analyses and trial sequential analysis were performed. RESULTS: The meta-analysis of 22 randomized controlled trials with 2566 patients showed that Dex significantly reduced the time to flatus [mean difference (MD):-7.19 h, P <0.00001), time to oral intake (MD: -6.44 h, P =0.001), time to defecation (MD:-13.84 h, P =0.008), LOS (MD:-1.08 days, P <0.0001), and PONV risk (risk ratio: 0.61, P <0.00001) without differences in hemodynamic stability and pain severity compared with the control group. Trial sequential analysis supported sufficient evidence favoring Dex for accelerating bowel function. Subgroup analyses confirmed the positive impact of Dex on the time to flatus across different surgical categories and sexes. However, this benefit has not been observed in studies conducted in regions outside China. CONCLUSIONS: Perioperative intravenous Dex may enhance postoperative gastrointestinal function recovery and reduce LOS, thereby validating its use in patients for whom postoperative ileus is a significant concern.

Efficacy of electroacupuncture in improving postoperative ileus in patients receiving colorectal surgery: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of electroacupuncture (EA) in improving postoperative ileus after colorectal surgery. METHODS: Electronic databases (e.g. Medline) were screened to identify randomized controlled trials that focused on the association between EA and postoperative ileus. Time to first flatus served as the primary outcome, while the secondary outcomes included time required for the recovery of other gastrointestinal functions (e.g. bowel sound recovery), time to tolerability of liquid/solid food, postoperative pain scores, risk of overall complications, and hospital length of stay. RESULTS: Our meta-analysis focusing on 16 studies with a total of 1562 patients demonstrated positive associations of EA with shorter times to the first flatus [mean difference (MD): -10.1 h, P <0.00001, n =1562], first defecation (MD: -11.77 h, P <0.00001, n =1231), bowel sound recovery (MD: -10.76 h, P <0.00001, n =670), tolerability of liquid (MD: -16.44 h, P =0.0002, n =243), and solid food (MD: -17.21 h, P =0.005, n =582) than those who received standard care. The use of EA was also correlated with a lower risk of overall complications (risk ratio:0.71, P =0.04, n =1011), shorter hospital length of stay (MD: -1.22 days, P =0.0001, n =988), and a lower pain score on postoperative days two (standardized MD: -0.87, P =0.009, n =665) and three (standardized MD: -0.45, P <0.00001, n =795), without a difference in time to first ambulation. CONCLUSION: Our findings showed an association between EA and enhanced gastrointestinal functional recovery and reduced pain severity following colorectal surgery, highlighting the potential benefits of incorporating EA into perioperative care to enhance recovery outcomes in this setting.

An enigma of hypothyroidism and hyponatremia coexistence: a nationwide population-based retrospective study.

INTRODUCTION: Hypothyroidism is a rare and possible cause of hyponatremia. However, the clinical epidemiology and risk of mortality (ROM) when they coexist still remain elusive. OBJECTIVES: We assessed the epidemiology and ROM among index patients with coexisting hypothyroidism and hyponatremia via a national population database. PATIENTS AND METHODS: This retrospective cohort study utilized Taiwan's National Health Insurance program database. Distributions of definite sociodemographic factors were analyzed. The annual incidence among the overall group and sex-subgroups was investigated. In addition, potential factors influencing the ROM were also evaluated. RESULTS: Of 4,549,226 patients from 1998 to 2015, a total of 3,140 index patients with concurrent hypothyroidism and hyponatremia were analyzed. The incidence rate increased tenfold from 1998 to 2015; average annual incidence rate was 174. Among the total participants, 57.1% were women; mean age was 72.6 ± 14.7 years and 88.8% were aged > 55 years. Although average length of stay (LOS) was 13.1 ± 15.4 days, the mortality group had significantly longer LOS than that in the survival group (12.9 days vs 22.2 days). Old age, catastrophic illness, cardiac dysrhythmia, and low hospital hierarchy were independent predictors of hospital mortality. The optimal LOS cutoff value for ROM prediction was 16 days. Index patients with LOS > 16 days increased ROM by 2.3-fold. CONCLUSIONS: Coexistent hypothyroidism and hyponatremia is rare, although the incidence increased gradually. Factors influencing the ROM, such as old age, underlying catastrophic status, cardiac dysrhythmia, hospital hierarchy, and LOS should be considered in clinical care.

Predictive Efficacy of the Perfusion Index for Hypotension following Spinal Anesthesia in Parturient Undergoing Elective Cesarean Section: A Systematic Review and Meta-Analysis.

This meta-analysis assessed the predictive efficacy of perfusion index for hypotension following spinal anesthesia (SA) in parturients undergoing elective cesarean section (CS). Electronic databases, including Google Scholar, EMBASE, Cochrane Library, and MEDLINE, were searched from inception to June 2023. The primary outcome was the diagnostic accuracy of the perfusion index in predicting the probability of perioperative hypotension following SA. The review included 12 studies involving 2009 patients, published between 2017 and 2023. The pooled sensitivity and specificity were 0.81 (95% confidence interval (CI) = 0.72-0.87) and 0.75 (95% CI = 0.67-0.82), respectively. Additionally, the pooled area under the curve (AUC) was calculated as 0.84 (95% CI = 0.81-0.87), suggesting a moderate to good accuracy of the diagnostic test. Using Fagan's nomogram plot, the positive likelihood ratio (LR) and negative LR were found to be 3 and 0.26, respectively. The results demonstrated that the perfusion index exhibited an acceptable level of accuracy in predicting perioperative hypotension after spinal anesthesia in parturients undergoing elective CS. These findings highlight the potential value of incorporating a perfusion index as a useful tool for clinicians to integrate into routine clinical practice, which necessitates further large-scale studies for verification.

Prevalence and risk factors of difficult mask ventilation: A systematic review and meta-analysis.

STUDY OBJECTIVE: This meta-analysis aimed at identifying the risk factors for and their strengths in predicting difficult mask ventilation (MV) through a systematic approach. DESIGN: Meta-analysis of observational studies. SETTING: Operating room. INTERVENTION: Airway- or patient-related risk factors for difficult MV reported in over 20% of eligible studies identified through literature review. PATIENTS: Adults receiving anesthetic induction with requirement of MV. MEASUREMENTS: Databases including EMBASE, MEDLINE, Google Scholar, and Cochrane Library were searched from inception to July 2022. The primary outcomes were the identification of commonly reported risk factors for MV and a comparison of their strengths in difficult MV prediction, while the secondary outcomes were the prevalence of difficult MV in the general population and those with obesity. MAIN RESULTS: Meta-analysis of 20 observational studies involving 335,846 patients identified 13 risk factors with predictive strengths (all p < 0.05): neck radiation (OR = 5.0, five studies, n = 277,843), increased neck circumference (OR = 4.04, 11 studies, n = 247,871), obstructive sleep apnea (OSA) (OR = 3.61, 12 studies, n = 331,255), presence of beard (OR = 3.35, 12 studies, n = 295,443), snoring (OR = 3.06, 14 studies, n = 296,105), obesity (OR = 2.99, 11 studies, n = 278,297), male gender (OR = 2.76, 16 studies, n = 320,512), Mallampati score III-IV (OR = 2.36, 17 studies, n = 335,016), limited mouth opening (OR = 2.18, six studies, n = 291,795), edentulous (OR = 2.12, 11 studies, n = 249,821), short thyroid-mental distance (OR = 2.12, six studies, n = 328,311), old age (OR = 2, 11 studies, n = 278,750), and limited neck movement (OR = 1.98, nine studies, n = 155,101). The prevalence of difficult MV was 6.1% (16 studies, n = 334,694) and 14.4% (four studies, n = 1152) in the general population and those with obesity, respectively. CONCLUSIONS: Our results demonstrated the strengths of 13 most common risk factors for predicting difficult MV, which may serve as an evidence-based reference for clinicians to incorporate into their daily practice.

RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury.

Acute lung injury (ALI) is characterised by severe pulmonary inflammation, alveolar-capillary barrier disruption, and pulmonary oedema. Therefore, establishing effective therapeutic targets for ALI prevention is crucial. The present study reports a novel function of RNF128 in regulating LPS-induced ALI. Severe lung damage and increased immune cell infiltration were detected in RNF128-deficient mice. In vitro experiments revealed that RNF128 inhibits neutrophil activation by binding to myeloperoxidase (MPO) and reducing its levels and activity. Moreover, RNF128 regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-κB activation, hence decreasing pro-inflammatory cytokines. Our results demonstrate for the first time that RNF128 is a negative regulator of MPO and TLR4 in neutrophils and alveolar macrophages, respectively. However, AAV9-mediated RNF128 overexpression alleviated lung tissue damage and reduced inflammatory cell infiltration. Thus, RNF128 is a promising therapeutic candidate for pharmacological interventions in ALI.

Gender-specific impacts of thigh skinfold thickness and grip strength for predicting osteoporosis in type 2 diabetes.

BACKGROUND: Diabetes with co-existing bone fragility or osteoporosis is common in elderly patients, whereas is frequently underestimated. METHODS: We conducted dual-energy x-ray absorptiometry (DXA) with 7-site skinfold (SF) and dominant hand grip strength measurements among patients with type 2 diabetes (T2DM) to assess their gender-specific associations. A total of 103 patients with T2DM (60 females and 43 males), aged between 50 and 80 years (median 68.0 years) were enrolled and 45 non-DM females were also included to compare with T2DM females. RESULTS: Our results revealed osteoporosis was negatively correlated with grip strength in both genders, negatively correlated with lean mass solely in males and negatively correlated with fat mass (particular the gynoid fat mass and thigh SF thickness) in females. Via performing multivariable stepwise logistic regression, we identified grip strength in both genders and thigh SF thickness in females as predictors for osteoporosis. Receiver operating characteristic curve analysis further disclosed 20.5 mm female thigh skinfold thickness, 18.1 kg female grip strength and 29.0 kg male grip strength as reasonable cutoff levels for predicting osteoporosis in the Taiwanese patients with T2DM. CONCLUSIONS: Patients with T2DM presented gender-specific associations between osteoporosis, body composition and grip strength. Grip strength and thigh SF thickness might serve as predictors for detection of osteoporosis in patients with T2DM.

The use of remimazolam versus propofol for induction and maintenance of general anesthesia: A systematic review and meta-analysis.

Background: The primary objective of this study was to compare the risk of hypotension, as well as the induction and recovery characteristics between remimazolam and propofol in patients receiving surgery under general anesthesia. Methods: The Embase, Medline, Google scholar, and the Cochrane Library databases were searched from inception to March 2022 for randomized controlled trials The primary outcome was the risk of post-induction hypotension between the two agents, while the secondary outcomes included anesthetic depth, induction efficacy, time to loss of consciousness (LOC), hemodynamic profiles, time to eye opening, extubation time as well as the incidence of injection pain and postoperative nausea/vomiting (PONV). Results: Meta-analysis of eight studies published from 2020 to 2022 involving 738 patients revealed a significantly lower risk of post-induction hypotension with the use of remimazolam compared to that with propofol [risk ratio (RR) = 0.57, 95% confidence interval (CI): 0.43 to 0.75, p < 0.0001, I2 = 12%, five studies, 564 patients]. After anesthetic induction, the anesthetic depth measured by bispectral index (BIS) was lighter in the remimazolam group than that in the propofol group (MD = 9.26, 95% confidence interval: 3.06 to 15.47, p = 0.003, I2 = 94%, five studies, 490 patients). The time to loss of consciousness was also longer in the former compared to the latter (MD = 15.49 s, 95%CI: 6.53 to 24.46, p = 0.0007, I2 = 61%, three studies, 331 patients). However, the use of remimazolam correlated with a lower risk of injection pain (RR = 0.03, 95%CI: 0.01 to 0.16, p < 0.0001, I2 = 0%, three studies, 407 patients) despite comparable efficacy of anesthetic induction (RR = 0.98, 95%CI: 0.9 to 1.06, p = 0.57, I2 = 76%, two studies, 319 patients). Our results demonstrated no difference in time to eye opening, extubation time, and risk of PONV between the two groups. Conclusion: Remimazolam was associated with a lower risk of post-induction hypotension after anesthetic induction compared with propofol with similar recovery characteristics. Further studies are required to support our findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/; Identifier: CRD42022320658.

New dimension on potential factors of successful pediatric peripheral intravenous catheterization.

BACKGROUND: Peripheral intravenous catheterization (PIVC) is pivotal to pediatric medical care; however, it is a challenging technique for pediatricians, and the parameters affecting successful pediatric PIVC establishment have not been fully investigated. METHODS: This prospective observational study collected data from pediatric patients aged less than 18 years who required PIVC. The participants were categorized into five groups for subgroup analysis: newborn, infant, toddler, pre-school, and student (children and adolescent). Data on demography, biochemistry, and PIVC executors were examined to elucidate the most powerful factors affecting the success of PIVC. RESULTS: A total of 935 peripheral venous cannulations conducted within 1 year were studied. Age-subgroup analysis showed the highest failure rate (FR) of PIVC in the infant group (18.4%). No significant difference in BMI standard deviation score was noted among the groups (p-value = 0.430). Compared with those for the success group, more attempts, longer completion time, and more medical staff were needed for the failure group (all p-values < 0.05). A high serum procalcitonin level was correlated with an increased FR (p-value = 0.016). In addition, the success rate was positively associated with the seniority of the operators, except for the 3-year experienced R3 group (93.5%) showing a higher success rate than the 4-year experienced CR group (84.2%). CONCLUSIONS: Difficulty in setting up PIVC was the greatest in infants and even greater than that in newborns. Even though seniority was a cardinal factor in successful PIVC, a high FR was still noted despite the lack of continuous and steady practice.

LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1.

PURPOSE: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells. METHODS: We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues. RESULTS: We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues. CONCLUSIONS: Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.

Analgesic efficacy and risk of low-to-medium dose intrathecal morphine in patients undergoing cardiac surgery: An updated meta-analysis.

Background: To evaluate the analgesic efficacy and risk of low-to-medium dose intrathecal morphine (ITM) (i.e., ≤0.5 mg) following cardiac surgery. Methods: Medline, Cochrane Library, Google scholar and EMBASE databases were searched from inception to February 2022. The primary outcome was pain intensity at postoperative 24 h, while the secondary outcomes included intravenous morphine consumption (IMC), extubation time, hospital/intensive care unit (ICU) length of stay (LOS), and ITM-associated side effects (e.g., respiratory depression). Subgroup analysis was performed on ITM dosage (low: <0.3 mg vs. medium: 0.3-0.5 mg). Results: Fifteen RCTs involving 683 patients published from 1988 to 2021 were included. Pooled results showed significantly lower postoperative 24-h pain scores [mean difference (MD) = -1.61, 95% confidence interval: -1.98 to -1.24, p < 0.00001; trial sequential analysis: sufficient evidence; certainty of evidence: moderate] in the ITM group compared to the controls. Similar positive findings were noted at 12 (MD = -2.1) and 48 h (MD = -1.88). Use of ITM was also associated with lower IMC at 24 and 48 h (MD: -13.69 and -14.57 mg, respectively; all p < 0.05) and early tracheal extubation (i.e., 48.08 min). No difference was noted in hospital/ICU LOS, and nausea/vomiting in both groups, but patients receiving ITM had higher risk of pruritus (relative risk = 2.88, p = 0.008). There was no subgroup difference in IMC except a lower pain score with 0.3-0.5 mg than <0.3 mg at postoperative 24 h. Respiratory depression events were not noted in the ITM group. Conclusion: Our results validated the analgesic efficacy of low-to-medium dose ITM for patients receiving cardiac surgery without increasing the risk of respiratory depression.

Comparison of video-stylet and conventional laryngoscope for endotracheal intubation in adults with cervical spine immobilization: A PRISMA-compliant meta-analysis.

BACKGROUND: Although minimization of cervical spine motion by using a neck collar or manual in-line stabilization is recommended for urgent tracheal intubation (TI) in patients with known or suspected cervical spine injury (CSI), it may worsen glottic visualization. The overall performance of video-stylets during TI in patients with neck immobilization remains unclear. The current meta-analysis aimed at comparing the intubation outcomes of different video-stylets with those of conventional laryngoscopes in patients with cervical immobilization. METHOD: The databases of Embase, Medline, and the Cochrane Central Register of Controlled Trials were searched from inception to June 2021 to identify trials comparing intubation outcomes between video-stylets and conventional laryngoscopes. The primary outcome was first-pass success rate, while secondary outcomes included overall success rate, time to intubation, the risk of intubation-associated sore throat, or tissue damage. RESULTS: Five randomized controlled trials published between 2007 and 2013 involving 487 participants, all in an operating room setting, were analyzed. The video-stylets investigated included Bonfils intubation fiberscope, Levitan FPS Scope, and Shikani optical stylet. There was no difference in first-pass success rate (risk ratio [RR] =1.08, 95% confidence interval [CI]: 0.89-1.31, P = .46], overall success rate (RR = 1.06, 95% CI: 0.93-1.22, P = .4), intubation time [mean difference = 4.53 seconds, 95% CI: -8.45 to 17.51, P = .49), and risk of tissue damage (RR = 0.46, 95% CI: 0.16-1.3, P = .14) between the 2 groups. The risk of sore throat was lower with video-stylets compared to that with laryngoscopes (RR = 0.45, 95% CI: 0.23-0.9, P = .02). CONCLUSION: Our results did not support the use of video-stylets as the first choice for patients with neck immobilization. Further studies are required to verify the efficacy of video-stylets in the nonoperating room setting.

Impact of Opioid-Free Anesthesia on Analgesia and Recovery Following Bariatric Surgery: a Meta-Analysis of Randomized Controlled Studies.

This meta-analysis aimed at exploring the impact of opioid-free anesthesia (OFA) on pain score and opioid consumption in patients undergoing bariatric surgery (BS). Literature search identified eight eligible trials. Forest plot revealed a significantly lower pain score (mean difference (MD) = - 0.96, p = 0.0002; 318 patients), but not morphine consumption (MD = - 5.85 mg, p = 0.1; 318 patients) at postoperative 24 h in patients with OFA than in those without. Pooled analysis also showed a lower pain score (p = 0.002), morphine consumption (p = 0.0003) in the postanesthetic care unit, and risk of postoperative nausea/vomiting (p = 0.0003) in the OFA group compared to the controls. In conclusion, this meta-analysis demonstrated that opioid-free anesthesia improved pain outcomes immediately and at 24 h after surgery without a beneficial impact on opioid consumption at postoperative 24 h. KEY POINTS: • Roles of opioid-free anesthesia (OFA) in bariatric surgery (BS) were investigated. • Outcomes included postoperative pain score, opioid use, and nausea/vomiting risk. • OFA was associated with lower 24-h pain score but not opioid consumption. • Lower pain score and opioid consumption were noted in the postanesthetic care unit. • OFA correlated with a lower risk of postoperative nausea/vomiting.

Generation and analysis of pseudohypoaldosteronism type II knock-in mice caused by a nonsense KLHL3 mutation in the Kelch domain.

Mutations in the Kelch-like 3 (KLHL3) gene are the most common cause of inherited pseudohypoaldosteronism type II (PHAII) featuring thiazide-sensitive hypertension and hyperkalemic metabolic acidosis. Although Klhl3R528H/+ knock-in (KI) mice carrying a missense mutation in the Kelch repeat domain have been reported, nonsense KLHL3 mutations in the same domain that cause PHAII have not been fully investigated in vivo. We generated and analyzed Klhl3 KI mice harboring a nonsense W523X mutation (corresponding to the human KLHL3 W470X mutation). Both heterozygous and homozygous Klhl3W523X/+ KI mice exhibited typical PHAII with low-renin hypertension, hyperkalemia with reduced renal potassium excretion, and hyperchloremic metabolic acidosis. Their kidney tissues showed the presence of Klhl3 mRNA and increased Klhl3 protein levels along with enhanced downstream Wnk1/4-Spak/Osr1-N(k)cc phosphorylation. Increased protein expression of total Spak, phosphor(p-)Spak, total Ncc, and p-Ncc from urinary extracellular vesicles (uEVs) also confirmed the activation of the Wnk-mediated Ncc pathway. In vitro studies showed that the human KLHL3 W470X mutation resulted in increased KLHL3 protein stability and disrupted its binding affinity for WNK1/4, leading to the attenuated degradation and increased abundance of total WNKs. In conclusion, nonsense Klhl3W523X/+ mice recapitulating PHAII phenotypes exhibit Klhl3 protein stability, abrogating its binding to Wnks, with enhanced Ncc expression in the kidney tissue and even in uEVs. Activation of the WNK-mediated Na+ -Cl- co-transporter reiterated the in vivo pathogenic role of nonsense KLHL3 mutations in PHAII.