Diabetic foot ulcers: A devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities

Diabetic foot ulcer is a devastating complication of diabetes mellitus and significant cause of mortality and morbidity all over the world and can be complex and costly. The development of foot ulcer in a diabetic patient has been estimated to be 19%-34% through their lifetime. The pathophysiology of diabetic foot ulcer consist of neuropathy, trauma and, in many patients, additional peripheral arterial disease. In particular, diabetic neuropathy leads to foot deformity, callus formation, and insensitivity to trauma or pressure. The standard algorithms in diabetic foot ulcer management include assessing the ulcer grade classification, surgical debridement, dressing to facilitate wound healing, off-loading, vascular assessment (status and presence of a chance for interventional vascular correction), and infection and glycemic control. Although especially surgical procedures are sometimes inevitable, they are poor predictive factors for the prognosis of diabetic foot ulcer. Different novel treatment modalities such as nonsurgical debridement agents, oxygen therapies, and negative pressure wound therapy, topical drugs, cellular bioproducts, human growth factors, energy-based therapies, and systematic therapies have been available for patients with diabetic foot ulcer. However, it is uncertain whether they are effective in terms of promoting wound healing related with a limited number of randomized controlled trials. This review aims at evaluating diabetic foot ulcer with regard to all aspects. We will also focus on conventional and novel adjunctive therapy in diabetic foot management.     

Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis

Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.     

Systemic immune inflammation index in patients with recurrent aphthous stomatitis

ObjectivesRecurrent Aphthous Stomatitis (RAS) a chronic idiopathic oral mucosal disease. But yet the etiology and pathogenesis of RAS are not exactly known, it is thought that inflammation play an important role in the pathogenesis. The aim of this study is to demonstrate the role of systemic inflammation among the possible etiological factors of RAS and to find the possible diagnostic correlation between Systemic Immune Inflammation Index (SII).MethodsPatients who were consulted the otolaryngology outpatient clinic and diagnosed with RAS between 2019–2021 were retrospectively analyzed. Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and SII values were calculated based on the results of complete blood count. Demographic and hematological parameters between control and RAS groups were compared. The statistical significance level was considered as <0.05.ResultsThere was no statistically significant difference between the control and RAS groups in terms of sex and age distributions (p = 0.566 and p = 0.173, respectively). SII, NLR and PLR values were significantly higher in the RAS group compared to the controls (p < 0.001, p < 0.001 and p = 0.001, respectively). A very strong correlation between SII and NLR, moderately strong correlation between SII and PLR and moderate correlation between NLR and PLR values were detected (respectively ρ: 0.813, 0.719, 0.532; p-values <0.001).ConclusionSII, NLR and PLR has significantly higher levels in the RAS group compared to the control group, that it supports the role of systemic inflammation in the etiopathogenesis of RAS. In addition, the results show that SII is a valuable marker for inflammation.Level of evidence4.     

胸段食管鳞癌术后复发模式及术后放疗靶区的研究北大核心

目的:研究胸段食管鳞癌术后复发模式,为术后放疗靶区勾画提供参考。方法:回顾分析我院2012年7月至2017年5月收治术后复发的81例胸段食管鳞癌患者的临床资料,参照AJCC第八版食管癌分期,将第1-8M站定义为上中纵隔淋巴结区,8Lo、9、15站定义为下纵隔淋巴结区,16-20站定义为上腹部淋巴结区。标记患者的复发部位,并分析局部复发、区域复发和远处转移的模式。结果:中位复发时间为12个月(2~103个月)。6例(7.4%)患者发生单纯局部复发,64例(79.0%)患者发生区域复发,11例(13.6%)患者发生远处转移。区域淋巴结复发中最高危的复发区域为上中纵隔淋巴引流区,此区域包含了82.8%的复发淋巴结,其次为上腹部淋巴结引流区(13.6%)。11例患者发生上腹部淋巴结复发,其中10(90.9%)例为胸下段,7例(63.6%)患者术后分期≥Ⅲ_(b)期。结论:胸段食管鳞癌术后复发模式以区域淋巴结复发为主,上中纵隔淋巴引流区为最高危复发区域,术后放疗靶区应重点包含。对于术后分期较晚的胸下段食管鳞癌,上腹部淋巴结引流区可能需要涵盖在放疗靶区内。吻合口、瘤床和下纵隔复发风险低,可不必常规涵盖在放疗靶区内。     

Effect of Yinqi Ointment on Wound Morphology and Growth Factor in Treating Diabetic Foot Ulcer

Objective: To investigate the effect of Yinqi ointment on wound morphology and growth factor in treating diabetic foot ulcer(DFU).Methods: From December 2016 to December 2017, 92 cases of DFU with deficiency of both Qi and Yin syndrome were randomly divided into treatment group and control group(44 cases in each group). The treatment group was treated with Yinqi ointment, while the control group was treated with mupirocin ointment. After 4 weeks of treatment, the ulcer healing effect, ulcer area, granulation tissue, epithelial tissue coverage,pain score, and dynamic analysis of vascular endothelial growth factor(VEGF), epidermis growth factor(EGF), and basic fibroblast growth factor(bFGF) in local granulation tissue were statistically analyzed before and after treatment in both groups. Results: The total effective rate was 88.37% in the treatment group and 74.42% in the control group. The wound reduction rate, epithelial tissue coverage rate, granulation tissue growth rate, and local pain relief rate in the treatment group were significantly superior to those in the control group(P 0.05). Through the local granulation detection, the treatment group and the control group have increased VEGF, EGF, and bFGF, but the treatment group increased the role of growth factor than the control group. Conclusion: Yinqi ointment can promote the healing of DFU, and its mechanism may be related to the increase of the content of growth factor in granulation tissue.     

基于数据挖掘对治疗口疮的成方制剂的用药规律分析*

目的分析治疗口疮的成方制剂的剂型、功能主治、组方用药规律及核心组合，为临床治疗口疮的辨证用药及新药研发提供参考。方法 收集《中华人民共和国卫生部药品标准·中药成方制剂》(以下简称《中药成方制剂》)、《中华人民共和国药典：2015年版》(以下简称2015年版《中国药典》)中治疗口疮的成方制剂的名称、处方、剂型、功能与主治，录入Microsoft Excel及中医传承辅助平台(V2.5)，统计用药频次；运用Apriori算法及关联规则对处方核心组合进行统计分析(支持度为10%，置信度100%)；采用熵聚类算法统计2-3个不同成分间的关联系数(支持度为8，惩罚度为2)；根据无监督的熵层次聚类法提取内在核心组合和新方组合。结果 挖掘得出86种成方制剂及其处方，以丸剂、散剂、片剂等多见，包含药物148味，使用频次较高为冰片、甘草、大黄、黄芩等，药物四气五味以苦寒为主，主要归肺胃心脾经，治疗证型较多为热毒炽盛证、热毒攻喉证等，常用核心配伍包括“黄芩-大黄”“黄连-甘草”等，挖掘得出新方组合“珍珠-川贝母-灯心草-天花粉-没药”等4首。结论 利用数据挖掘分析治疗口疮的成方制剂的组方规律，由核心药物组合成新方，可为临床辨证使用及研发治疗口疮成方制剂、新药提供依据和参考。     

Evaluation of timolol maleate gel for management of hard-to-heal chronic venous leg ulcers. Phase II randomised-controlled study

BackgroundVenous leg ulcers (VLUs) often take a very long time to heal. Timolol maleate has been reported as displaying efficacy in healing of VLUs.ObjectivesTo evaluate the efficacy of timolol maleate gel in the management of hard-to-heal VLUs and to assess its safety as a topical agent during 12 weeks of use in combination with conventional treatment.MethodsA prospective, phase-II randomised-controlled trial with a sample size based on Fleming's one-stage design (P0 = 0.25, P1 = 0.45, alpha = 0.1, beta = 0.2) was planned. Patients with VLUs present for ≥ 24 weeks and with ≥ 50% granulation tissue were included. One drop of sustained-release timolol gel (Timoptol® LP 0.5%, Santen, Tampere, Finland) per 6 cm² VLU area was applied every 2 days for 12 weeks in timolol-treated patients, as adjuvant therapy to the standard care protocol (interface dressing and multilayer venous compression). Controls received standard care alone. The primary endpoint was to obtain ≥ 40% reduction in ulcer area at week 12 (W12).ResultsForty-three patients were randomised to the study, with 40 receiving at least one treatment and included in the analysis: 21 timolol-treated patients and 19 controls (females: 70%; median age: 72.5 [range 35–93] years). At W12, ≥ 40% ulcer-area reduction was achieved in 14/21 (67%) timolol-treated patients vs. 6/19 (32%) controls. No serious adverse events occurred. Local wound infections not requiring systemic antibiotics occurred in 5 cases in the timolol group and in one case in the controls.ConclusionsThese results support the benefit and safety of using timolol maleate to manage hard-to-heal VLUs, but confirmation is required in a larger multicentre randomised phase-III study.     

Homocysteine might increase the risk of recurrence in patients presenting with primary cerebral infarction

Purpose: Although hyperhomocysteinemia (Hhcy) is a risk factor for cerebral infarction, its effect on recurrent cerebral infarction is less-defined. We aimed to investigate the association of Hhcy and increased risk of recurrent cerebral infarct.

Materials and methods: From 2011 to 2013, we recruited 231 primary cerebral infarct patients that were divided to a Hhcy group (n?=?105) and a control group (n?=?126) according to plasma homocysteinemia (Hcy) levels exceeding 15?μmol/L. In this prospective study, risk factors such as gender, age, blood lipid and glucose levels, history of diabetes, high blood pressure, smoking habits and plasma Hhcy levels were determined. A three-year follow-up compared differences in cerebral infarction recurrence rates. Statistical analyses identified whether plasma Hhcy levels were an independent risk factor for recurrent cerebral infarction.

Results: Triglyceride and low-density lipoprotein (LDL) levels in the Hhcy group were significantly higher than controls, and cerebral infarct recurrence rates in the Hhcy group exceeded control subject rates through the three-year follow-up (p?=?.021, p?=?.036 and p?=?.025). Cox proportional hazards modeling showed that elevated Hhcy levels (hazard ratio [HR]?=?3.062, p?<?.001), increased age (HR?=?1.069, p?<?.01), circulating triglyceride levels (HR?=?1.686, p?=?.048), and relative National Institutes of Health Stroke (NIHSS) score (HR?=?1.068, p?=?.016) were risk factors for recurrent cerebral infarction.

Conclusions: Level of Hhcy was a risk factor for recurrent cerebral infarction. Further, particular demographic and clinical outcomes including age, relative NIHSS scores, and circulating triglyceride levels were markedly associated with the occurrence of cerebral infarction.