Limited evidence to support demineralized bone matrix in foot and ankle surgical procedures:A systematic review

BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.

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.

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.

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.

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.

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.

SEPARATED FRAMES

In this paper we shall offer a separation axiom for frames inspired by the Hausdorff separation axiom for topological spaces. We call it separated condition. This is a condition on topology OX equivalent to the T O space X being Hausdorff. The class of separated frames includes that of strong Hausdorff frames and that of S frames. We shall show that the class of separated frames is a class closed under the formation of coproducts and subspaces, and the space Fil( L ) is Hausdorff for any separated frame L . Therefore there is a contravariant adjunction between the category TOP 2 of Hausdorff topological spaces and the category FRAM 2 of separated frames.

A Sort of Gray-scale Morphological Dilations and Erosions

We introduce first a sort of gray-scale morphological dilations and erosions, which might have some further applications in image analysis. Then we show that the dilation and the erosion defined here form adjunctive pairs. The duality between the dilation and the erosion and some other properties, such as homothety, of these operators are discussed the Commuting property with translation and as well.

Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice

AIM:To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice.METHODS:To establish a solid tumor model,5.0 × 10 6 /mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice(6-12 wk old,18-22 g).When the tumors reached a size of 100 mm 3,the animals were treated as indicated,and the mice were randomly assigned to seven groups(n = 10 each).After ten days of treatment,blood samples were collected from mouse eyes,and serum was harvested by centrifugation.Mice were sacrificed,and the whole body,tumor,spleen and thymus were weighed immediately.The rate of tumor inhibition and organ indexes were calculated.The expression levels of serum cytokines,P-glycoprotein(P-GP) and multidrug resistance(MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay,Western blotting,and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction,respectively.RESULTS:The tumor inhibition rates in the treatment groups of Adriamycin(ADM) + Astragalus polysaccharides(APS)(50 mg/kg),ADM + APS(100 mg/kg),and ADM + APS(200 mg/kg) were significantly higher than in the ADM group(72.88% vs 60.36%,P = 0.013;73.40% vs 60.36%,P = 0.010;77.57% vs 60.36%,P = 0.001).The spleen indexes of the above groups were also significantly higher than in the ADM group(0.65 ± 0.22 vs 0.39 ± 0.17,P = 0.023;0.62 ± 0.34 vs 0.39 ± 0.17,P = 0.022;0.67 ± 0.20 vs 0.39 ± 0.17,P = 0.012),and the thymus indexes of the ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups were significantly higher than in the ADM group(0.20 ± 0.06 vs 0.13 ± 0.04,P = 0.029;0.47 ± 0.12 vs 0.13 ± 0.04,P = 0.000).APS was found to exert a synergistic antitumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD.The expression of interleukin-1α(IL-1α),IL-2,IL-6,and tumor necrosis factor-α(TNF-α) was significantly higher in the ADM + APS(50 mg/kg),ADM + APS(100 mg/kg) and ADM + APS(200 mg/kg) groups than in the ADM group;and IL-10 was significantly lower in the above groups than in the ADM group.APS could increase IL-1α,IL-2,IL-6,and TNF-α expression and decrease IL-10 levels.Compared with the ADM group,APS treatment at a dose of 50-200 mg/kg could downregulate MDR1 mRNA expression in a dose-dependent manner(0.48 ± 0.13 vs 4.26 ± 1.51,P = 0.000;0.36 ± 0.03 vs 4.26 ± 1.51,P = 0.000;0.21 ± 0.04 vs 4.26 ± 1.51,P = 0.000).The expression level of P-GP was significantly lower in the ADM + APS(200 mg/kg) group than in the ADM group(137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg,P = 0.023).CONCLUSION:APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice.This may be related to its ability to enhance the expression of IL1α,IL-2,IL-6,and TNF-α,decrease IL-10,and downregulate MDR1 mRNA and P-GP expression levels.

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.

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.

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.

Adjuncts to colonic cleansing before colonoscopy

Pre-procedural cleansing of the bowel can maximize the effectiveness and efficiency of colonoscopy.Yet,efficacy of the current gold standard colonic preparation method-high-volume oral administration of purgative agents 12-24 h prior to the procedure-is limited by several factors,such as patient compliance(due to poor palatability and inconvenience of the dosing regimen)and risks of complications(due to drug interactions or intolerance).Attempts to resolve these limitations have included providing adjunctive agents and methods to promote the colonic cleansing ability of the principal purgative agent,with the aim of lessening unpleasant side effects(such as bloating)and reducing the large ingested volume requirement.Several promising adjunctive agents are bisacodyl,magnesium citrate,senna,simethicone,metoclopramide,and prokinetics,and each are being investigated for their potential.This review provides an up to date summary of the reported investigations into the potencies and weaknesses of the key adjuncts currently being applied in clinic as supplements to the traditional bowel preparation agents.While the comparative analysis ofthese adjuncts showed that no single agent or method has yet achieved the goal of completely overcoming the limitations of the current gold standard preparation method,they at least provide endoscopists with an array of alternatives to help improve the suboptimal efficacy of the main cleansing solutions when used alone.To aid in this clinical endeavor,a subjective grade was assigned to each adjunct to indicate its practical value.In addition,the systematic review of the currently available agents and methods provides insight into the features of each that may be overcome or exploited to create novel drugs and strategies that may become adopted as effective bowel cleansing adjuncts or alternatives.

Does mindfulness meditation improve attention in attention deficit hyperactivity disorder?

Attention deficit hyperactivity disorder(ADHD) manifests by high levels of inattention, impulsiveness and hyperactivity. ADHD starts in childhood and results in impairments that continue into adulthood. While hyperactivity declines over time, inattention and executive function difficulties persist, leading to functional deficits. Adolescents and adults with ADHD have pervasive impairment in interpersonal and family relationships. They may develop addiction, delinquent behavior and comorbid psychiatric disorders. Despite advances in diagnosis and treatment, persistent residual symptoms are common, highlighting the need for novel treatment strategies. Mindfulness training, derived from Eastern meditation practices, may improve self-regulation of attention. It may also be a useful strategy to augment standard ADHD treatments and may be used as a potential tool to reduce impairments in patients with residual symptoms of ADHD. Clinically, this would manifest by an increased ability to suppress task-unrelated thoughts and distractions resulting in improved attention, completion of tasks and potential improvement in occupational and social function.

Promoting axonal regeneration following nerve surgery： a perspective on ultrasound treatment for nerve injuries

Nerve injury is often associated with limited axonal regeneration and thus leads to delayed or incomplete axonal reinnervation.As a consequence of slow nerve regeneration,target muscle function is often insufficient and leads to a lifelong burden.Recently,the diagnosis of nerve injuries has been improved and likewise surgical reconstruction has undergone significant developments.However,the problem of slow nerve regeneration has not been solved.In a recent meta-analysis,we have shown that the application of low-intensity ultrasound promotes nerve regeneration experimentally and thereby can improve functional outcomes.Here we want to demonstrate the experimental effect of low intensity ultrasound on nerve regeneration,the current state of investigations and its possible future clinical applications.

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.

Steroids in Maxillofacial Space Infection: A Retrospective Cohort Study

Maxillofacial space infection (MSI) is one of the most common conditions encountered in oral and maxillofacial surgery clinics. Early recognition and proper management of MSI could prevent a life-threatening event. Objectives: To report a series of MSI managed with antibiotics, surgical intervention and exogenous steroids as an adjunct, highlighting functional improvement following steroid administration. Methods: A retrospective cohort study was carried out from December 2013 to September 2016, involving 30 patients (n = 30, 22 males, 8 females) diagnosed with MSI. All patients were initially managed with intravenous empirical antibiotics, analgesics and removal of potential source of infection. A course of 3 doses of IV Dexamethasone 8 mg at an interval of 8 hours was started during the first day of hospital admission. Results: This series reports 30 patients presenting with MSI, who received prompt antibiotics and 3 doses of steroids as inpatients. Significant clinical improvement was noted in the form of amelioration of pain, rapid reduction in edema, and improved trismus, shortening hospital stay to an average of 3.5 days, and omission of surgical intervention in 50% of our cases. No adverse effects or drug reaction was noted. Conclusion: In conclusion, the value of synergistic use of corticosteroids with antibiotics in management of MSI is significant. Despite these promising findings, there is scarce evidence in the literature to fully support the use of corticosteroids in abscess management. The role of corticosteroids in treatment of MSI should be explored further.

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.