Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines

The coronavirus disease(COVID-19)pandemic has led to a global struggle to cope with the sheer numbers of infected persons,many of whom require intensive care support or eventually succumb to the illness.The outbreak is managed by a combination of disease containment via public health measures and supportive care for those who are affected.To date,there is no specific anti-COVID-19 treatment.However,the urgency to identify treatments that could turn the tide has led to the emergence of several investigational drugs as potential candidates to improve outcome,especially in the severe to critically ill.While many of these adjunctive drugs are being investigated in clinical trials,professional bodies have attempted to clarify the setting where the use of these drugs may be considered as off-label or compassionate use.This review summarizes the clinical evidence of investigational adjunctive treatments used in COVID-19 patients as well as the recommendations of their use from guidelines issued by international and national organizations in healthcare.

Adjunctive Peony-Glycyrrhiza decoction for antipsychotic-induced hyperprolactinaemia:a meta-analysis of randomised controlled trials

Background Hyperprolactinaemia is a common adverse effect of antipsychotics （APs）. The results of Peony-Glycyrrhiza decoction （PGD） as a potentially useful adjunctivetreatment for hyperprolactinaemia are inconsistent.Aim This meta-analysis of randomised controlled trials （RCTs） examined the effcacy and safety of adjunctive PGDtherapy for AP-induced hyperprolactinaemia.Methods English （PubMed, Embase, Cochrane Library, PsycINFO） and Chinese （Chinese National Knowledge Infrastructure, Wanfang Data） databases were systematicallysearched up to 10 June 2018. The inclusion criteria were based on PICOS-Participants： adult patients with schizophrenia; Intervention： PGD plus APs; Comparison： APs plus placebo or AP monotherapy; Outcomes： effcacy and safety; Study design： RCTs. The weighted mean difference （WMD） and risk ratio （RR） along with their 95% CIs were calculated using Review Manager （RevMan） V.5.3 software.Results Five RCTs （n=450） were included and analysed. Two RCTs （n=140） were double-blind and four RCTs （n=409） reported ‘random’ assignment with specifc description. The PGD group showed a signifcantly lower serum prolactin level at endpoint than the control group （n=380, WMD： ？32.69 ng/mL （95% CI -41.66 to 23.72）, p〈0.00001, I2=97%）. Similarly, the superiority of PGD over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale （n=403, WMD： -0.62 （95% CI -2.38 to 1.15）, p=0.49, I^2=0%）. There were similar rates of all-cause discontinuation （n=330, RR 0.93 （95% CI 0.63 to 1.37）, p=0.71, I^2=0%） and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from ‘very low’ （14.3%）, ‘low’ （42.8%）, ‘moderate’ （14.3%）, to ‘high’ （28.6%）.Conclusions Current evidence supports the adjunctive use of PGD to suppress elevated prolactin and improve prolactin-induced symptoms without signifcant adverse events in adult patients with AP-induced hyperprolactinaemia. High-quality RCTs with longer duration are needed to confrm these fndings.

Pharmacologic adjunctive to insulin therapies in type 1 diabetes:The journey has just begun

Treatment of type 1 diabetes(T1 D) is currently based exclusively on insulin replacement therapy. However, there is a need for better glycemic control, lower hypoglycemia rates, more effective weight management, and further reduction of cardiovascular risk in people with T1 D. In this context, agents from the pharmaceutical quiver of type 2 diabetes are being tested in clinical trials, as adjunctive to insulin therapies for T1 D patients. Despite the limited amount of relevant evidence and the inter-class variability, it can be said that these agents have a role in optimizing metabolic control, assisting weight management and reducing glycemic variability in people with T1 D. Specific safety issues, including the increased risk of hypoglycemia and diabetic ketoacidosis, as well as the effects of these treatments on major cardiovascular outcomes should be further assessed by future studies, before these therapeutic choices become widely available for T1 D management.

Evaluation of the Protégé^(TM) stent in the treatment of carotid artery stenosis with adjunctive use of a filter Embolic Protection Device (PROCAR)-one-month follow-up data on 77 patients

Objective The trial was designed to evaluate the safety and performance of the ev3 Protégé TM stent in the treatment of de novo or re-stenotic common and/or internal carotid artery stenoses with adjunctive use of a CE-marked filter embolic protection device.Methods This study was a prospective multi-center, single-arm trial. Between June and October 2003, 77 patients were enrolled in 8 investigational centers throughout Europe. The primary endpoint was the incidence of Major Neurological Events (MANE) through one month. Other endpoints were the ability to properly place the stent, and primary patency and MANE after six months. Eligible for the study were patients with a de novo or restenotic target lesion located in the common and/or internal carotid artery (>70% stenosis for asymptomatic and >50% stenosis for symptomatic patients). The ev3 Spider (Embolic Protection Filter was used in 75 of 77 cases. Results In 76 out of the 77 patients (99%), the stent could be successfully implanted with a residual stenosis ≤30% as criterion. Of the 74 patients that had a carotid ultrasound at one month follow-up, none had a re-stenosis of the target lesion. There were three MANEs during or immediately after the procedure (3.9%), two were major and one was a minor stroke. There were eight severe complications (9.1%); six of these happened during or immediately after the procedure and were related to the procedure, none was related to the device. They are resolved without sequelae. No deaths have occurred.Conclusions The Protégé stent is safe and performs well in the treatment of carotid artery stenosis. The technical success rate for placement of the Protégé stent as assessed by the residual stenosis post implant was very high and all stents were successfully deployed. The incidence of MANE was comparable with that in other recent carotid stent studies and still lower than standard CEA.

The efficacy and tolerability of lamotrigine adjunctive/monotherapy in patients with partial seizures refractory to poly-AEDs

Objective： This study was designed as an open-label trial to assess the effects of changing the antiepileptic drugs （AEDs） regimen to lamotrigine （LTG） as adjunctive/monotherapy in patients with partial seizures who were dissatisfied with their drug regimen because of intractable seizures. Methods： The patients were recruited from mulficenters using the following criteria： age≥ 18 years; at least 3 seizures per month during the last 16 weeks; previous use of at least 3 AEDs. The study involved a baseline phase and 2 experimental phases： LTG was first added to the regimen, and then patients could gradually change to LTG monotherapy if their seizures were reduced by at least 50 percent/month. Tolerability, the primary end point, was assessed using the Liverpool Adverse Experience Profile （LAEP）. Secondary end points included quality of life, as measured with the Quality of Life in Epilepsy-31 inventory. Reductions in seizures from baseline throughout each phase were also analyzed. Results： One hundred and fourteen patients aged between 18 and 52 years （age 27.8___ 13.2 years; 71 men and 43 women） were enrolled. After adding LTG, 105 patients （92.11%） Completed adjunctive therapy. Upon completion of the adjunctive phase, mean improvement from baseline was 2.6 points on the LAEP （p=0.037）. The overall score on the QOLIE-31 improved by 8.49 points from baseline （p=0.023）. At the end of the trial, 26 （22.81%） of patients completed LTG monotherapy, and 65 patients （57.02%） experienced at least 50% reduction in seizure frequency compared to baseline, The mean improvement from baseline was 5.1 points on the LAEP （p=0.0059）, and the overall score on the QOLIE-31 score improved by 12,72 points from baseline（p=0,0071）. Twenty-two （19.30%） patients reported adverse effects and 9 patients discontinued participation in the trial because of adverse effects. Conclusion： For patients with partial seizures who were dissatisfied with their AED regimen because of intractable seizures, adding LTG to the drug regimen was well tolerated and effective in improving the quality of life and controlling seizures. Furthermore, switching to LTG monotherapy was associated with further improvement.

Selective laser trabeculoplasty as adjunctive treatment for open-angle glaucoma vs following incisional glaucoma surgery in Chinese eyes

BACKGROUND Selective laser trabeculoplasty(SLT)is a relatively safe and effective therapy in lowering intraocular pressures(IOP)for glaucoma.AIM To study the long-term effects of SLT on IOP and number of glaucoma medications used in Chinese eyes.METHODS This is a retrospective study in which 75 eyes of 70 patients with open-angle glaucoma(OAG,n=36)and eyes with prior glaucoma surgery(PGS,n=39)were included.Changes in mean IOP and number of glaucoma medications used evaluated at 1 d,1 wk,1 mo,3 mo,6 mo,12 mo,and 36 mo after laser treatment.RESULTS All patients(33 male,37 female)were Chinese.The mean age was 44.34±16.14years.Mean pre-SLT IOP was 22.75±2.08 mmHg in OAG and 22.52±2.62 mmHg in PGS.Mean IOP was significantly reduced 1 d,1 wk,1 mo and 3 mo after laser treatment(P<0.05,respectively).Whereas,there were no significant differences between baseline and SLT treated groups at the 6th month both in OAG(P=0.347,P>0.05)and in PGS(P=0.309,P>0.05).Six months after SLT treatment,some patients received retreatment of SLT or were given more topical IOP-lowering medication to control the IOP.By the end of our study,the average IOP decreased to 20.73±1.82 mmHg in OAG and 20.49±1.53 mmHg in PGS groups.The number of glaucoma medications used was significantly reduced until the end of 3 years compared to baseline.CONCLUSION SLT could reduce IOP as adjunctive treatment both in OAG and PGS groups.SLT significantly reduced the number of glaucoma medications used 3-years following treatment in glaucoma patients.

Adjunctive pharmacotherapy and treatment patterns among initiators of SSRI therapy for major depressive disorder: A cohort study using a primary care database

Objective: Adjunctive therapy is often used for treatment of major depressive disorder (MDD) following an inadequate response to an antidepressant. However, there is little information regarding its practice within primary care in the United Kingdom (UK). Objectives of the study were to examine incidence and predictors of adjunctive pharmacotherapy among patients with MDD treated with selective serotonin reuptake inhibitors (SSRIs) by UK general practitioners (GPs). Methods: The General Practice Research Database was used to identify 15,274 MDD patients prescribed first-line treatment with SSRIs from 2006-2008 (latest patient follow-up towards end of 2010). Treatment trajectories were identified and classified as adjunctive therapy, combination therapy, drug switches, dose increases, and restart of therapy. Incidence and predictors of adjunctive therapy were assessed, and healthcare resource utilization was evaluated. Results: Overall incidence of adjunctive therapy was 3.07/100 person years (95% CI 2.90-3.25). Patients prescribed adjunctive therapy were more likely to be female (IRR 1.15, p = 0.03), of higher age (IRRs 1.51-2.60, p ≤ 0.001), and had a greater depression severity score (IRR 1.02, p = 0.003). Presence of irritable bowel syndrome (IRR 1.53, p = 0.001), and an increasing Charlson Comorbidity Index (IRR 1.15, p = 0.01) were associated with a higher incidence of adjunctive therapy. MDD-related general practitioner consultations among patients who received adjunctive therapy was lower compared with patients receiving other treatment interventions (IRRs 0.79 - 0.87, p ≤ 0.001). Conclusions: Adjunctive therapy is infrequently utilized relative to other treatment options for management of MDD among patients who are inadequate responders to their SSRI treatments in UK primary care;however some groups are more likely to receive adjunctive therapy than others.

Long-Term, Open-Label, Safety Study of Edivoxetine as Adjunctive Treatment for Adult Patients with Major Depressive Disorder Who Were Partial Responders to Selective Serotonin Reuptake Inhibitor Treatment in Japan

Edivoxetine is a highly selective norepinephrine reuptake inhibitor (NRI) that has been investigated in short-term studies as adjunctive therapy to?selective serotonin reuptake inhibitor antidepressants (SSRIs) in patients with major depressive disorder (MDD) who were partial responders to their SSRIs. This 52-week open-label study investigated the safety and tolerability of longer-term treatment with adjunctive edivoxetine in patients with MDD in Japan, who had completed one of two placebo-controlled acute studies of edivoxetine as adjunctive therapy to SSRIs. All patients continued on their stable dose of SSRI. Two hundred eighty-eight patients were enrolled and assessed for up to 1 year using standard safety and tolerability measures. Of these, 195 patients previously received only placebo in the parent study and, therefore, were first exposed to edivoxetine in this study. Approximately 46% of patients completed the study. The most frequently cited (>5%) reasons for discontinuation were sponsor decision (19.4%, which included patients discontinued due to early study termination), adverse event (17.4%) and subject decision (8.7%). Adverse events leading to discontinuation in more than 2 patients (>1%) were palpitations, vomiting, hepatic function abnormal, hypertension, nausea, and tachycardia. Treatment-emergent elevations in diastolic blood pressure and pulse were at least twice that reported in the literature for non-Asian patients. Twenty percent of patients had sustained elevations in pulse. Treatment-emergent changes in laboratory measures were small and not clinically meaningful. Assessment across all safety measures in this study indicated that the safety profile of edivoxetine was consistent with that expected for a selective NRI.

Topical Application of Ascorbic Acid Solution as an Adjunctive Method of Periodontal Therapy among Wet Snuff Users after Prosthodontics Therapy

Background: During several years, ascorbic acid (vitamin C) played a significant role in the health of periodontal tissues. The goals of prosthodontics management are to restore the missing teeth, provide the loss of teeth functions, and establish acceptable dental esthetics, and there are some evidences revealing the passive effects of snuff on the results of prosthodontics and periodontal treatment, so the present study is performed to evaluate the outcomes of topical application of ascorbic acid solution as an adjunctive method of periodontal therapy among wet sniff users after prosthodontics therapy. Methods: The clinical situation was evaluated in 150 moderate periodontitis patients after conventional periodontal and prosthodontics therapy. They were selected from outpatient clinics, college of dentistry, King Khalid University, and from some hospitals Ministry of Health in Tabuk, Jazan and Aseer regions. The study was conducted from September 2020 to December 2020. The time of post-treatment assessment was one year. The study was included 50 patients who don’t use wet snuff as a group I (GI) (control group), 50 patients wet snuff users as group II (GII), and 50 patients wet snuff users were treated with topical application of ascorbic acid solution as group III (GIII). The participants were aged over 20 years, with a mean age of 35 years. The duration of using wet snuff was at least one year. Plaque index (PLI), gingival index (GI), clinical attachment loss (CAL) were recorded at baseline (first visit), then after 4 weeks (second visit) and after 6 weeks (third visit) of conventional periodontal therapy and topical application of ascorbic acid solution. Statistical analysis was done using ANOVA test and paired t-test. Results: According to statistical analysis, there was the inclination of decrease in the mean and standard deviation of plaque index (PLI) from 2.8 ± 1.4 to 2.5 ± 0.51, and 2.7 ± 0.33 in group II, and decrease from 2.7 ± 0.34 to 2.5 ± 0.23 and 2.6 ± 0.65 in group III. Similarly in the gingival index (GI), there was a decrease in the mean and standard deviation from 2.8 ± 0.52 to 2.3 ± 0.62 and 2.5 ± 0.51 in group II and a decrease from 2.5 ± 0.8 to 2.3 ± 0.58 and 2.4 ± 0.47 in group III. Moreover, there was a decrease in the mean and standard deviation of clinical attachment loss (CAL) from 4.5 ± 0.26 to 3.9 ± 0.83 and 4.2 ± 0.83 in group II and from 4.2 ± 0.31 to 3.8 ± 0.46 and 3.8 ± 0.31 in group III;less than group I without significance differences (p > 0. 05) in all study groups at baseline and after 4 weeks, and 6 weeks of follow up except CAL. Conclusion: The results of our study displayed that periodontal parameters vary among wet snuff users after topical application of ascorbic acid solution as an adjunctive method of periodontal therapy

Role of adjunctive nonpharmacological strategies for treatment of rapid-cycling bipolar disorder

Rapid-cycling bipolar disorder(RCBD)is a phase of bipolar disorder defined by the presence of≥4 mood episodes in a year.It is a common phenomenon characterized by greater severity,a predominance of depression,higher levels of disability,and poorer overall outcomes.It is resistant to treatment by conventional pharmacotherapy.The existing literature underlines the scarcity of evidence and the gaps in knowledge about the optimal treatment strategies for RCBD.However,most reviews have considered only pharmacological treatment options for RCBD.Given the treatment-refractory nature of RCBD,nonpharmacological interventions could augment medications but have not been adequately examined.This review carried out an updated and comprehensive search for evidence regarding the role of nonpharmacological therapies as adjuncts to medications in RCBD.We identified 83 reviews and meta-analyses concerning the treatment of RCBD.Additionally,we found 42 reports on adjunctive nonpharmacological treatments in RCBD.Most of the evidence favoured concomitant electroconvulsive therapy as an acute and maintenance treatment.There was preliminary evidence to suggest that chronotherapeutic treatments can provide better outcomes when combined with medications.The research on adjunctive psychotherapy was particularly scarce but suggested that psychoeducation,cognitive behavioural therapy,family interventions,and supportive psychotherapy may be helpful.The overall quality of evidence was poor and suffered from several methodological shortcomings.There is a need for more methodologically sound research in this area,although clinicians can use the existing evidence to select and individualize nonpharmacological treatment options for better management of RCBD.Patient summaries are included to highlight some of the issues concerning the implementation of adjunctive nonpharmacological treatments.

Efficacy of Cordyceps sinensis as an adjunctive treatment in hemodialysis patients: a systematic review and Meta-analysis

OBJECTIVE: To evaluate current evidence on the efficacy and safety of Cordyceps sinensis(cordyceps)or its fermented products used as an adjunctive treatment in patients undergoing maintenance hemodialysis.METHODS: The Cochrane Central Register of Controlled Trials(CENTRAL), EMBASE, MEDLINE, China National Knowledge Infrastructure(CNKI) and Wanfang Database were searched for relevant randomized controlled trials up to March 2016. Two review authors independently selected trials for inclusion,extracted data, assessed the methodological quality and rated the quality of evidence with the Grading of Recommendations, Assessment, Development and Evaluation approach.RESULTS: Twelve studies involving 655 participants were included. Evidence of low to moderate-quality showed that cordyceps plus conventional treatment compared to conventional treatment alone significantly improved C-reactive protein [standardized mean difference(SMD)-0.61; 95% confi-dence intervals(CI)-1.00 to-0.22], high-sensitivity C-reactive protein [weighted mean difference(WMD)-3.44 mg/L; 95% CI-3.89 to-2.99], serum albumin(WMD 3.07 g/L; 95% CI 1.59 to 4.55),malondialdehyde(WMD-1.95 nmol/L; 95% CI-2.24 to-1.66), and hemoglobin(WMD 9.56 g/L;95% CI 3.65 to 15.47) levels. However, there was no significant improvement for serum creatinine and low-density lipoprotein cholesterol. Overall, most trials either did not monitor adverse events or poorly documented them.CONCLUSION: Given the small number of trials included, the unclear methodological quality of the included trials, and the high heterogeneity in pooled analyses, the evidence obtained in this review is insufficient to recommend the use of cordyceps as adjunctive treatment in hemodialysis patients.

Research progress in spasmodic torticollis rehabilitation treatment

Spasmodic torticollis(ST)is a focal dystonia that affects adults,causing limited muscle control and impacting daily activities and quality of life.The etiology and curative methods for ST remain unclear.Botulinum toxin is widely used as a firstline treatment,but long-term usage can result in reduced tolerance and adverse effects.Rehabilitation therapy,with its minimal side effects and low potential for harm,holds significant clinical value.This article explores the effectiveness of adjunctive therapies,including exercise therapy,transcranial magnetic stimulation,shockwave therapy,neuromuscular electrical stimulation,vibration therapy,electromyographic biofeedback,and acupuncture,in the treatment of ST.The aim is to provide clinicians with additional treatment options and to discuss the efficacy of rehabilitation therapy for ST.

Advancing oral cancer care:Insights from Tongluo Jiedu prescription

This editorial highlights the study which investigated the potential of traditional Chinese medicine(TCM)as an adjunctive therapy in oral cancer management.The study included 80 patients with oral cancer to evaluate the effects of the Tongluo Jiedu prescription on inflammatory stress markers,peripheral blood T-cell subsets,and overall immune function.The results indicated that Tongluo Jiedu substantially enhances immune function and reduces oxidative stress,thereby aiding in patient recovery and potentially minimizing treatment-related complications.This editorial discusses the broader implications of these findings for oral cancer care and emphasizes the importance of integrating TCM principles into modern oncology practices.

Analysis of the Effect of Non-Invasive Positive Pressure Ventilation in Emergency Treatment of Severe Bronchial Asthma with Respiratory Failure

Objective:This study aims to evaluate the clinical efficacy of non-invasive positive pressure ventilation(NIPPV)in patients with severe bronchial asthma combined with respiratory failure.Methods:90 patients with severe bronchial asthma combined with respiratory failure between September 2022 and December 2023 were selected for the study and randomly divided into the experimental group(NIPPV-assisted treatment)and the control group.The differences between the two groups were compared in terms of total effective rate of treatment,days of clinical symptom disappearance,days of hospitalization,lung function indexes,incidence of adverse reactions,and quality of life.Results:Patients in the experimental group had a significantly higher total effective rate of treatment(97.78%)than the control group(75.56%).In terms of pulmonary function indexes,patients in the experimental group showed significant improvement after treatment,especially the increase in forced expiratory volume and forced vital capacity,while these improvements were not as obvious in the control group.In addition,the incidence of adverse reactions was significantly lower in the experimental group than in the control group,suggesting that the application of NIPPV is relatively safe.Quality of life assessment also showed that patients in the experimental group had significantly better quality of life than the control group after treatment.Conclusion:This study demonstrated the effectiveness of NIPPV as an adjunctive treatment for severe bronchial asthma combined with respiratory failure.NIPPV can improve lung function,reduce the incidence of adverse effects,increase the overall effectiveness of the treatment,and contribute to the improvement of patients'quality of life.Therefore,NIPPV should be regarded as an effective and safe treatment in clinical management,especially in patients with severe bronchial asthma combined with respiratory failure,where its application has potential clinical significance.

Digesting gluten with oral endopeptidases to improve the management of celiac disease

In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals.Although avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa.As villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid complications.Oral administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under investigation.The article is about the utility of one endopeptidase isolated from Aspergillus niger.We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

Role of artificial intelligence in colorectal cancer

The sphere of artificial intelligence(AI)is ever expanding.Applications for clinical practice have been emerging over recent years.Although its uptake has been most prominent in endoscopy,this represents only one aspect of holistic patient care.There are a multitude of other potential avenues in which gastrointestinal care may be involved.We aim to review the role of AI in colorectal cancer as a whole.We performed broad scoping and focused searches of the applications of AI in the field of colorectal cancer.All trials including qualitative research were included from the year 2000 onwards.Studies were grouped into pre-operative,intra-operative and post-operative aspects.Preoperatively,the major use is with endoscopic recognition.Colonoscopy has embraced the use for human derived classifications such as Narrow-band Imaging International Colorectal Endoscopic,Japan Narrow-band Imaging Expert Team,Paris and Kudo.However,novel detection and diagnostic methods have arisen from advances in AI classification.Intra-operatively,adjuncts such as image enhanced identification of structures and assessment of perfusion have led to improvements in clinical outcomes.Post-operatively,monitoring and surveillance have taken strides with potential socioeconomic and environmental savings.The uses of AI within the umbrella of colorectal surgery are multiple.We have identified existing technologies which are already augmenting cancer care.The future applications are exciting and could at least match,if not surpass human standards.

拟连续Domain及其子范畴间的伴随关系

基于Smyth幂 Domain的构造,本文证明了连续半格范畴 CSL（分别地,有界完备连续Domain范畴CBD）是拟连续Domain范畴QCONT（分别地,Coherent拟连续 Domain范畴QCCOH）的反射子范畴.反例表明,连续 Domain范畴CONT作为范畴 QCONT的真子范畴并非其反射子范畴.所有结果均被进一步推广到拟代数Domain范畴.

Cardioprotection and pharmacological therapies in acute myocardial infarction: Challenges in the current era

In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification ofseveral promising pharmacological(cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proofof-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.

Current status of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a rare primary liver cancer with a global increasing trend in recent years. Symptoms tend to be vague and insidious in development, often are diagnosed at an advanced stage when only palliative approaches can be used with a median survival rate of months. Comparing with HCC, ICC tends to spread to lymph nodes early, and is rarely limited to the regional lymph nodes, with a frequent postoperative recurrence. Surgery is the only choice of curative therapy for ICC, but recently no consensus has been established for operation. Thus, more data from multiple centers and more cases are needed. Generally speaking, current adjunctive therapy cannot clearly improve survival. Further research is needed to find more effective radio- and chemotherapeutic regimens.

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

AIM： To identify the proportion, causes and the nature of drug-induced liver injury （DILI） in patients with no- tably elevated alanine aminotransferase （ALT）. METHODS： All the inpatients with ALT levels above 10 times upper limit of normal range （ULN） were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS： A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury （n = 46, 35.7%）, DILl （n = 25, 19.4%） and malignancy （n = 21, 16.3%） were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury （14.5 5.6 ULN vs 32.5 ：I： 30.7 ULN, P = 0.001）. Among DILI patients, one （4%） case was classified as definite, 19 （76%） cases were clas- sified as probable and 5 （20%） as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 （92%） cases and mixed in 2 （8%）. The extent of severity of liver injury was mild in 21 （84%） patients and moderate in 4 （16%）. Before discharge, 10 （40%） patients were recovered and the other 15 （60%） were improved. The improved patients tended to have a higher peak ALT （808 ＋ 348 U/L vs 623 ＋ 118 U/L, P = 0.016） and shorter treatment duration before discharge （8 ＋ 6 d vs 28 ~ 12 d, P = 0.008） compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 （32%） cases, followed by glucocorticoids in 6 （24%） cases. Twenty-four （96%） cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs （e.g., glycyr- rhizinate）, antioxidants （e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin）, polyene phospha- tidyl choline and herbal extracts （e.g., protoporphyrin disodium and silymarin）. Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio （OR） 32.7, 95%CI （2.8-374.1）,CONCLUSION： DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.