Exanthema

Exanthema
  • 文章类型: Journal Article
    艾滋病是一种不治之症,在非洲很常见。CD4计数低于240的HIV/AIDS患者应服用延长寿命的ARV药物。抗逆转录病毒药物对一些患者有严重的副作用,可以通过治疗或将患者的药物转换为没有或没有严重副作用的药物来处理。然而,在这样做之前,更多地了解导致副作用的情况是至关重要的。我们使用统计分析来联系1A的副作用,2A,根据医院数据记录,根据患者的社会和人口统计学特征制定5A治疗方案。对患者主卡(2011-2014)进行回顾性审查,以评估与不同ARV方案相关的不良反应。在901名出现副作用的患者中,31-40岁女性占65.37%,男性占34.63%。相对而言,1A方案显示比2A和5A方案更多的副作用。年龄,性别和职业与治疗方案症状显著相关(p<0.05)。不像男人,女性有以下额外的副作用;咳嗽,与脂肪营养不良相比,周围神经病变和腿部疼痛。我们的结果表明,与脂肪营养不良相比,老年人(50岁以上)不太可能出现皮疹和其他症状(RRR=0.973)。Further,咳嗽的概率(0.0021,p<0.05),或皮疹(0.0021,p<0.05),作为副作用,平均而言,随着年龄的增加,性别和体重相同。周围神经病变的概率(0.0042,p<0.01),然而,随着年龄的增长。了解HIV患者的社会人口统计学和患者的治疗方案副作用可用于适当管理严重的ARV副作用。考虑到ARV方案中导致特定副作用的化学物质的治疗考虑可以针对具有相容的社会人口统计学特征的患者。
    AIDS is an incurable disease that is common in Africa. Patients with HIV/AIDS having a CD4 count of less than 240 are put on life prolonging ARV drugs. The ARVs have serious side effects on some patients which may be handled by treating them or switching patient\'s drug to one with no or less serious side effects. However, before doing this, more understanding of the circumstances that lead to a side effect is vital. We use statistical analyses to link side effects of 1A, 2A, and 5A treatment regimens to the patient\'s social and demographic characteristics based on hospital data records. A retrospective review of patients\' master cards (2011-2014) was done to assess adverse effects associated with different ARV regimens. Out of the 901 patients that showed side effects, 65.37% were females aged 31-40 and 34.63% were males. Comparatively, 1A regimen showed more side effects than 2A and 5A regimens. Age, gender and occupation correlated significantly with regimen symptoms (p< 0.05). Unlike men, women had the following extra side effects; cough, peripheral neuropathy and leg pains as compared to lipodystrophy. Our results show that old people (50years+) are less likely to get skin rash and other symptoms compared to lipodystrophy (RRR=0.973). Further, the probability of either having cough (0.0021, p< 0.05), or skin rash (0.0021, p< 0.05), as a side effect, on average, decreases as age increases with the same sex and weight. The probability of having peripheral neuropathy (0.0042, p< 0.01), however, increases with age. Knowledge of HIV patient\'s socio-demographics and the patient\'s regimen side effects can be utilised to appropriately manage severe ARV side effects. A therapy consideration that takes into account chemicals in ARV regimen responsible for specific side effects can be directed to patients with compatible socio-demographic characteristics.
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  • 文章类型: Multicenter Study
    背景:水痘是一种由猴痘病毒引起的特征性皮疹的病毒性疾病。2022年,水痘在世界各地蔓延,2023年初,韩国开始了通过国内传播的流行病。本研究旨在总结韩国水痘患者的临床特点。
    方法:这是一项在韩国四家医院进行的多中心回顾性研究。对2022年6月1日至2023年5月26日期间入住研究医院并于2023年6月30日出院的所有诊断为Mpox的成年患者进行了审查。
    结果:纳入60例患者,占研究期间韩国报告的水痘病例的65.9%。中位年龄为32岁,97%(58/60)的患者为男性。总的来说,85%(51/60)的患者报告其性取向为同性恋或双性恋。最常见的传播途径是性或密切接触(55/60)。每个患者都有皮疹,88%(53/60)有全身症状。总的来说,42%(25/60)的患者患有人类免疫缺陷病毒,25%(15/60)的患者伴有性传播感染。仅在两名患者中发现了严重的水痘表现。
    结论:韩国的水痘患者主要是年轻的成年男性,通过性接触感染。临床结果良好。
    BACKGROUND: Mpox is a viral illness with a characteristic skin rash caused by the monkeypox virus. In 2022, Mpox spread throughout the world, and an epidemic through domestic transmission started in South Korea in early 2023. This study aimed to summarize the clinical features of Mpox patients in South Korea.
    METHODS: This is a multicenter retrospective study conducted at four hospitals in South Korea. All adult patients diagnosed with Mpox who were admitted to the study hospitals between June 1, 2022 and May 26, 2023 and were discharged by June 30, 2023 were reviewed.
    RESULTS: Sixty patients were included, accounting for 65.9% of Mpox cases reported in South Korea during the study period. Median age was 32 years and 97% (58/60) of patients were male. In total, 85% (51/60) of patients reported their sexual orientation as homosexual or bisexual. The most common route of transmission was sexual or close contact (55/60). Every patient had a skin rash and 88% (53/60) had constitutional symptoms. In total, 42% (25/60) of patients had human immunodeficiency virus and 25% (15/60) had concomitant sexually transmitted infections. Severe manifestations of Mpox were identified in only two patients.
    CONCLUSIONS: Mpox patients in South Korea were mainly young adult males and were infected through sexual contact. The clinical outcomes were favorable.
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    文章类型: Journal Article
    BACKGROUND: The outbreak of monkeypox occurred in 2022 and led to a fast spread of the disease worldwide. The goal of this study is to describe the epidemiological, clinical, virological and evolving characteristics of the disorder.
    METHODS: We conducted a retrospective, observational and analytical study between July and October, 2022, in a Dermatology Unit.
    RESULTS: 124 subjects were included. Mean age was 31.5 years, 123 (99.2%) were men and 75 (60.5%) were HIV positive. The main transmission route was sexual and the incubation period was 7 days. The onset of the rash were the genitalia and perianal region in 74.2% of cases, and median time elapsed until the last scab fell off was 16 days. All patients developed a vesicular rash and 86.3% of them had systemic symptoms. Disease was moderate in 68.5% of patients and complications occurred most often when systemic symptoms and/or disseminated skin disease were present. Proctitis was the most frequent complication (59.4%) and its greater incidence was seen in the population with HIV. No significant difference was observed in real-time PCR cycle threshold values with regards to type of sample or duration of disease. Survival rate was 99.2% and other concomitant sexually transmitted infections were detected in 33.8% of patients.
    CONCLUSIONS: It is important to suspect the disease in subjects with high-risk sexual practices and a consistent clinical presentation. Swab samples of lesions as well as of scabs have proven useful for the diagnosis.
    Introducción: El brote de viruela símica 2022 se extendió rápidamente por todo el mundo. El objetivo del presente trabajo es describir las características epidemiológicas, clínicas, evolutivas y virológicas. Métodos: Estudio retrospectivo, observacional y analítico entre julio-octubre del 2022 en pacientes atendidos en una Unidad de Dermatología. Resultados: Se incluyeron 124 individuos. La mediana de edad fue de 31.5 años, siendo 123 (99.2%) hombres y 70 (60.5%) HIV positivos. La vía principal de contagio fue la transmisión sexual y el período de incubación de 7 días. Las lesiones se iniciaron en la región genital y perianal en el 74.2% de los casos y el tiempo hasta la caída de la última costra presentó una mediana de 16 días. Todos desarrollaron exantema vesiculoso, el 86.3% de los individuos presentó síntomas sistémicos. La enfermedad fue moderada en el 68.5% de los pacientes y las complicaciones se observaron con mayor frecuencia en aquellos con síntomas sistémicos y/o enfermedad diseminada. Proctitis fue la complicación más destacada (59.4%) y su mayor incidencia se observó en la población con HIV. No hubo diferencias significativas en los valores de Ct de la qPCR al evaluar tipo de muestra procesada o tiempo de evolución de la enfermedad. La sobrevida fue del 99.2% y en el 33.8% de los pacientes se detectaron otras infecciones concomitantes de transmisión sexual. Discusión: Se debe sospechar la enfermedad en individuos con cuadro compatible y prácticas sexuales de riesgo. Las muestras de hisopado de lesiones y de costra resultaron útiles para el diagnóstico.
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  • 文章类型: Clinical Trial, Phase III
    Deucravitinib,一个口头,选择性,变构酪氨酸激酶2抑制剂,在日本被批准用于成人斑块(PP)患者,广义脓疱(3GPP),和红皮病性(EP)银屑病对常规全身治疗反应不足。这项批准是基于全球3期POETYKPSO-1和PSO-2试验的结果,在这些试验中,与安慰剂相比,在中度至重度斑块状银屑病的成人中,deucravitinib的疗效结果显着改善。这里描述的结果来自POETYKPSO-4,一个开放标签,单臂,3期试验(NCT03924427),评估了ducravitinib6mg每日一次在日本成年PP患者中的疗效和安全性,3GPP,或EP。共同主要终点是银屑病面积和严重程度指数(PASI75)与静态医师全球评估评分为0(明确)或1(几乎明确)(sPGA0/1)且在第16周时与基线相比至少改善2分的患者比例。无响应者归因用于缺失数据。疗效反应,不良事件(AE),和严重AE(SAE)记录长达52周。74例患者接受了治疗(PP,n=63;3GPP,n=3;EP,n=8)。在第16周,76.2%,66.7%,和37.5%的PP患者,3GPP,EP,分别,获得了PASI75和82.5%,0.0%,50.0%达到sPGA0/1。反应总体维持至第52周。不良事件发生在74.6%的PP患者中,100%的患者,和87.5%的EP患者。最常见的AE是鼻咽炎和痤疮。严重不良事件和中止率很低。没有死亡。Deucravacitinib在日本中度至重度PP患者和有限数量的3GPP或EP患者中有效且耐受性良好。
    Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in Japan for adult patients with plaque (PP), generalized pustular (GPP), and erythrodermic (EP) psoriasis who have had an inadequate response to conventional systemic therapies. This approval is based on results from the global phase 3 POETYK PSO-1 and PSO-2 trials in which deucravacitinib was associated with significantly improved efficacy outcomes compared with placebo in adults with moderate to severe plaque psoriasis, and results described here from POETYK PSO-4, an open-label, single-arm, phase 3 trial (NCT03924427), which evaluated the efficacy and safety of deucravacitinib 6 mg once daily in adult Japanese patients with PP, GPP, or EP. The coprimary endpoints were the proportion of patients achieving a ≥75% reduction from baseline in the Psoriasis Area and Severity Index (PASI 75) and a static Physician\'s Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) with at least a two-point improvement from baseline at week 16. Nonresponder imputation was used for missing data. Efficacy responses, adverse events (AEs), and serious AEs (SAEs) were recorded for up to 52 weeks. Seventy-four patients were treated (PP, n = 63; GPP, n = 3; EP, n = 8). At week 16, 76.2%, 66.7%, and 37.5% of patients with PP, GPP, and EP, respectively, had achieved PASI 75, and 82.5%, 0.0%, and 50.0% had achieved sPGA 0/1. Responses were overall maintained through week 52. AEs occurred in 74.6% of patients with PP, 100% of patients with GPP, and 87.5% of patients with EP. The most common AEs were nasopharyngitis and acne. Rates of SAEs and discontinuations were low. There were no deaths. Deucravacitinib was effective and well tolerated in Japanese patients with moderate to severe PP and in a limited number of patients with GPP or EP.
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  • 文章类型: Journal Article
    在中国,2~3级免疫相关皮疹可能导致免疫治疗中断.皮质类固醇(CS)是主要的治疗方法,但并不总是有效的。清热祛湿的外部应用,以清-Re-Li-Shi公式(QRLSF)表示,在过去的5年中,我们医院一直用于治疗免疫相关的皮肤不良事件(ircAE)。目的探讨其治疗2~3级皮疹的疗效和安全性。
    对我院2019年12月至2022年12月的2至3级免疫相关性皮疹患者进行了回顾性研究。这些患者接受QRLSF治疗。临床特征,治疗结果,并对健康相关生活质量(HrQoL)进行分析。
    纳入30例2-3级皮疹患者(中位发病时间:64.5天)。24例(80%)的皮肤病变恢复到1级,中位时间为8天。伴随症状也得到改善,中位时间为3至4天。添加抗组胺药(AH)并没有增加QRLSF的疗效(AH+QRLSF:75.00%vsQRLSF:83.33%,P=.66)。无论患者以前是否接受过CS治疗,QRLSF治疗的疗效均无明显差异(未治疗人群:88.24%与治疗人群:69.23%,P=.36)。在1个月的随访中,2例(8.33%)复发。就HrQoL而言,QRLSF治疗可显着降低Skindex-16所有领域的中位数得分,包括症状(39.58vs8.33,P<0.0001),情绪(58.33vs15.48,P<0.0001),功能(46.67vs13.33,P<.0001)和复合(52.60vs14.06,P<.0001)。
    外部应用清热除湿被证明是对此类患者的有效且安全的治疗方法。在未来,需要高质量的试验来确定其在ircAE领域的临床应用。
    UNASSIGNED: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash.
    UNASSIGNED: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed.
    UNASSIGNED: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn\'t increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001).
    UNASSIGNED: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.
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  • 文章类型: English Abstract
    Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q1, Q3) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.
    目的: 了解带状疱疹就诊病例疼痛变化情况及其影响。 方法: 将2017年1月1日至2019年12月31日密云区医院门诊首次就诊并被诊断为带状疱疹(HZ)的3 487例病例纳入研究。登记对象资料并发放记录卡,病例自行记录疼痛时间和出疹时间等信息。分别在病例出现皮疹后21、90、180和365 d进行电话随访,内容包括住院情况、出疹与疼痛出现的部位、开始和结束时间,以HZ简易疼痛量表(ZBPI)评价疼痛对生活的影响。 结果: 纳入分析的2 999例HZ病例年龄为(53±16)岁,其中男性1 377例(45.91%),50岁及以上1 903例(63.45%),出疹后21 d轻、中和重度疼痛分别占20.87%(626例)、37.98%(1 139例)和33.81%(1 014例),无痛感和不适感者仅占5.07%(152例),无痛感但有不适感者占2.27%(68例)。疼痛部位多与皮疹部位一致,胸背部和腰腹部多见,分别占35.58%(1 067例)和29.18%(875例),其次为四肢和面颈部,分别占16.74%(502例)和16.40%(492例)。HZ病例疼痛天数的M(Q1,Q3)为14(8,20)d,带状疱疹后神经痛(PHN)发生率为6.63%(171/2 580)(剔除出疹后90 d拒访或失访的419例病例)。HZ病例出疹后21 d内疼痛评分为(5.19±2.73)分,其中PHN病例疼痛评分为(7.61±2.13)分,明显高于非PHN病例[(5.04±2.69)分](P<0.001)。HZ病例出疹21 d后日常活动、情绪、行走能力、工作、社交、睡眠和娱乐方面受影响比例范围为60.79%~83.83%,以睡眠所受影响较大(83.83%),其中PHN病例在ZBPI量表中疼痛与生活维度的影响评分范围为4.59~7.61分,高于非PHN病例(2.49~5.04)(t值范围为8.86~11.67,均P<0.001)。 结论: 带状疱疹就诊病例出疹后疼痛比例高,PHN和50岁及以上带状疱疹病例疼痛更明显,对生活影响更大。.
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  • 文章类型: Multicenter Study
    Ieramilimab,人源化抗LAG-3单克隆抗体,在1期研究中,与抗PD-1抗体司他珠单抗联合用药耐受性良好。这项2期研究旨在进一步研究联合治疗在选定的晚期(局部晚期或转移性)实体恶性肿瘤患者中的疗效和安全性。符合条件的非小细胞肺癌(NSCLC)患者,黑色素瘤,肾细胞癌(RCC),间皮瘤,和三阴性乳腺癌(TNBC)根据之前的抗PD-1/L1治疗(抗PD-1/L1未治疗或抗PD-1/L1预处理)进行分组。患者每3周接受ieramilimab(400mg),然后接受司他珠单抗(300mg)。主要终点是客观缓解率(ORR),还有安全,药代动力学,和生物标志物评估。235名患者中,142例未经抗PD-1/L1治疗,93例用抗PD-1/L1抗体预处理。在抗PD-1/L1未治疗的患者以及用抗PD1/L1预处理的黑素瘤和RCC患者的所有适应症中都可以看到持久的反应(>24个月)。最常见的研究药物相关不良事件是瘙痒(15.5%),疲劳(10.6%),首次使用抗PD-1/L1和疲劳(18.3%)的患者出现皮疹(10.6%),皮疹(14.0%),抗PD-1/L1预处理患者的恶心(10.8%)。生物标记物评估表明,在有反应的患者中,基线时T细胞发炎的基因特征表达较高。在所有入选适应症中,一些患者对治疗的反应是持久的(>24个月),和安全性发现与以往和目前探索LAG-3/PD-1阻断的研究一致.
    Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along with safety, pharmacokinetics, and biomarker assessments. Of 235 patients, 142 were naive to anti-PD-1/L1 and 93 were pretreated with anti-PD-1/L1 antibodies. Durable responses (>24 months) were seen across all indications for patients naive to anti-PD-1/L1 and in melanoma and RCC patients pretreated with anti-PD1/L1. The most frequent study drug-related AEs were pruritus (15.5%), fatigue (10.6%), and rash (10.6%) in patients naive to anti-PD-1/L1 and fatigue (18.3%), rash (14.0%), and nausea (10.8%) in anti-PD-1/L1 pretreated patients. Biomarker assessment indicated higher expression of T-cell-inflamed gene signature at baseline among responding patients. Response to treatment was durable (>24 months) in some patients across all enrolled indications, and safety findings were in accordance with previous and current studies exploring LAG-3/PD-1 blockade.
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  • 文章类型: Case Reports
    背景技术免疫球蛋白A(IgA)血管炎是一种小血管血管炎,其特征在于IgA免疫复合物主要沉积在皮肤中。肾脏,和胃肠道。虽然它主要影响儿童,成人病例与更严重的表现有关。有证据表明,感染性触发因素在其病因中起着关键作用。通常,它遵循一个自我限制的过程,不需要干预。案例报告我们介绍了一个51岁的男人,他出现了斑丘疹,关节痛,和腹痛。检查发现下肢和腹部有紫癜性皮疹。下肢双工超声检查发现右腿深静脉血栓形成(DVT)。皮疹的皮肤活检证实了IgA血管炎的诊断,显示血管周围嗜中性粒细胞浸润和IgA复合物沉积。粪便研究显示与隐孢子虫和贾第鞭毛虫共感染。患者接受泼尼松锥度治疗,症状明显改善。结论该病例强调了隐孢子虫作为IgA血管炎的潜在触发因素。并发感染的存在强调了感染与IgA血管炎发展之间复杂的相互作用。与贾第鞭毛虫共感染表明可能涉及继发感染,进一步复杂化的疾病的病因。DVT的观察表明IgA血管炎和血栓前状态之间可能存在联系。本报告有助于扩大IgA血管炎触发因素和相关并发症的知识,指导临床医生诊断和处理类似病例,同时强调对有这些症状的成年人保持警惕的重要性。
    BACKGROUND Immunoglobulin A (IgA) vasculitis is a small-vessel vasculitis characterized by the deposition of IgA immune complexes primarily in the skin, kidneys, and gastrointestinal tract. While it predominantly affects children, cases in adults are associated with more severe manifestations. Evidence suggests that infectious triggers play a pivotal role in its etiology. Often, it follows a self-limiting course and doesn\'t necessitate intervention. CASE REPORT We present the case of a 51-year-old man who presented with a maculopapular rash, arthralgia, and abdominal pain. An examination revealed a purpuric rash on lower extremities and abdomen. A lower extremity duplex ultrasound identified deep vein thrombosis (DVT) in the right leg. Skin biopsy of the rash confirmed the diagnosis of IgA vasculitis, demonstrating perivascular neutrophilic infiltrate and IgA complex deposition. Stool studies revealed co-infection with Cryptosporidium and Giardia. The patient was treated with a prednisone taper with significant improvement in symptoms. CONCLUSIONS This case highlights the potential role of Cryptosporidium as a trigger for IgA vasculitis. The presence of concurrent infections underscores the complex interplay between infections and the development of IgA vasculitis. The co-infection with Giardia suggests that a secondary infection may be involved, further complicating the disease\'s etiology. The observation of DVT suggests a possible link between IgA vasculitis and a prothrombotic state. This report serves to expand the knowledge of IgA vasculitis triggers and associated complications, guiding clinicians in diagnosing and managing similar cases while emphasizing the importance of vigilance in adults with these symptoms.
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  • 文章类型: Clinical Trial, Phase I
    背景:Sapanisertib(CB-228/TAK-228)是一种有效的,选择性ATP竞争,mTORC1/2的双重抑制剂。我们报告初步安全性,与二甲双胍联用的效果。
    方法:标准治疗难以治疗的晚期转移性实体瘤患者,有/无mTOR/AKT/PI3K通路改变,每天服用sapanisertib3mg或4mg,并服用二甲双胍1至3次(500mg-1500mg)。
    结果:在4个队列中招募了30名患者(3mg/500mg;3mg/1000mg,4mg/1000mg;4mg/1500mg)。19人是女性(63%),中位年龄为57岁(范围:30-77岁).肿瘤类型包括肉瘤(6),乳房(4),卵巢(4)。最常见的基因组改变包括PIK3CA(27%),PTEN(17%),AKT1/2(10%),mTOR(10%)。在可评估反应的30名患者中,4名患者获得部分反应(PR);15名患者获得稳定的疾病(SD)作为最佳反应。疾病控制率(PR+SD)为63%。公关的响应者中,3/4pts有PTEN突变(3/5pts入组PTEN突变有PR);2/4pts有共同突变(pt有平滑肌肉瘤有PTEN和TSC;pt有乳腺癌有PTEN和STK11);1/4pts有AKT和mTOR突变。(G)3-5级治疗相关不良事件包括高血糖(4/30;13%)疲劳(2/30;7%)高甘油三酯血症(1/30;3%)皮疹(2/20;7%),腹泻(2/30;7%),肌酐增加(1/30;3%),酸中毒(1/30;3%)。4mg/1000mg被定义为最年夜耐受剂量。
    结论:mTORC1/2抑制剂sapanisertib联合二甲双胍的安全性总体上是可以耐受的,在具有PTEN/AKT/mTOR通路改变的晚期恶性肿瘤患者中观察到抗肿瘤活性。
    Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of 5\'-AMP-activated protein kinase (AMPK) suggesting combination therapy may enhance antitumor activity of sapanisertib. We report preliminary safety, tolerability, and efficacy from the dose-escalation study of sapanisertib in combination with metformin in patients with advanced solid tumors.
    Patients with advanced metastatic solid tumors resistant or refractory to standard treatment, with and without mTOR/AKT/PI3K pathway alterations, received sapanisertib 3 or 4 mg daily together with metformin once to three times daily (500-1,500 mg). All patients underwent 14-day titration period for metformin in cycle 1. Tumor measurements were performed following cycle 2 and subsequently every 8 weeks.
    A total of 30 patients were enrolled across four cohorts (3 mg/500 mg; 3 mg/1,000 mg, 4 mg/1,000 mg; 4 mg/1,500 mg). 19 were female (63%), median age was 57 (range: 30-77), all were Eastern Cooperative Oncology Group performance status 1. Tumor types included sarcoma (6), breast (4), ovarian (4), head and neck (3), colorectal (2), lung (2), renal cell (2), endometrial (2), gastroesophageal junction (1), prostate (1), stomach (1), urachus (1), and cervical cancer (1). Median number of prior lines of therapy was 4. Most common genomic alterations included PIK3CA (27%), PTEN (17%), AKT1/2 (10%), mTOR (10%). Of 30 patients evaluable for response, 4 patients achieved partial response (PR); 15 patients achieved stable disease (SD) as best response. Disease control rate (PR+SD) was 63%. Of the responders in PR, 3 of 4 patients had documented PTEN mutations (3/5 patients enrolled with PTEN mutations had PR); 2 of 4 of patients in PR had comutations (patient with leiomyosarcoma had both PTEN and TSC; patient with breast cancer had both PTEN and STK11); 1 of 4 patients in PR had AKT and mTOR mutation; tumor types included leiomyosarcoma (n = 2), breast (n = 1), and endometrial cancer (n = 1). Most common treatment-emergent adverse events included nausea, anorexia, diarrhea, and rash. Grade (G) 3-5 treatment-related adverse events included hyperglycemia (4/30; 13%), fatigue (2/30; 7%), hypertriglyceridemia (1/30; 3%), rash (2/20; 7%), diarrhea (2/30; 7%), creatinine increase (1/30; 3%), acidosis (1/30; 3%). No dose-limiting toxicities (DLT) were reported in the 3 mg/500 mg cohort. One of 6 patient had DLT in the 3 mg/1,000 mg cohort (G3 diarrhea) and 2 of 11 patients had DLTs in the 4 mg/1,500 mg cohort (G3 fatigue, G3 rash). 4 mg/1,000 mg was defined as the MTD.
    The safety profile of mTORC1/2 inhibitor sapanisertib in combination with metformin was generally tolerable, with antitumor activity observed in patients with advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations.
    Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, next-generation dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of AMPK suggesting combination therapy may enhance antitumor activity of sapanisertib. This dose-escalation study of sapanisertib and metformin in advanced solid tumors and mTOR/AKT/PI3K pathway alterations, demonstrates safety, tolerability, and early clinical activity in advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations.Clinical trial information: NCT03017833.
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  • 文章类型: Review
    背景:NLRP12相关自身炎性疾病(NLRP12-AID)是由NLRP12基因变异体引起的常染色体显性遗传自身炎性疾病。我们的目的是报告一组中国成人NLRP12-AID患者的表型和基因型。
    方法:20例患者在进行全外显子组测序后被诊断为NLRP12-AID,并被纳入我们的队列。人口统计信息,我们收集并评估了临床数据和治疗反应.对NLRP12-AID进行了文献综述,总结了临床特征和突变位点,并与我们的队列进行了比较.
    结果:在20名NLRP12-AID患者中,NLRP12-AID的主要临床特征包括发热,皮肤皮疹,关节痛/关节炎,咽炎/扁桃体炎,淋巴结病,肌痛和腹痛/腹泻。检测到13种NLRP12变体为F402L,G39V,R1030X,R7G,E24A,Q90X,A218V,A259V,W581X,G729R,R859W,c.-150T>C和c.*126G>C.14例患者使用糖皮质激素,免疫抑制剂13例,托珠单抗2例。17名患者对治疗反应良好。与来自其他国家的50名NLRP12-AID患者相比,中国患者外显子3变异较少,皮疹发生率较高,咽炎/扁桃体炎和淋巴结病。在所有70名NLRP12-AID患者中,携带非外显子-3变异的患者眼部受累频率较高,咽炎/扁桃体炎,头痛和淋巴结病比外显子-3变异。
    结论:这是世界上最大的NLRP12-AID队列,并鉴定了NLRP12的7种新变体。与其他国家的患者相比,中国成年NLRP12-AID患者的非特异性症状更多,例如咽炎/扁桃体炎和淋巴结肿大,其中外显子-3变异体较少出现可能是一个可能的原因。
    BACKGROUND: NLRP12-associated autoinflammatory disease (NLRP12-AID) is an autosomal dominant autoinflammatory disorder caused by variants of NLRP12 gene. We aimed to report a cohort of Chinese adult patients with NLRP12-AID and summarised phenotypes and genotypes.
    METHODS: Twenty patients were diagnosed with NLRP12-AID after performing whole-exome sequencing and were included in our cohort. Demographic information, clinical data and treatment response were collected and evaluated. A literature review of NLRP12-AID was performed, and the clinical features and mutated sites were summarised and compared with our cohort.
    RESULTS: Among the 20 NLRP12-AID patients, the main clinical features of NLRP12-AID included fever, cutaneous rash, arthralgia/arthritis, pharyngitis/tonsillitis, lymphadenopathy, myalgia and abdominal pain/diarrhoea. Thirteen NLRP12 variants were detected as F402L, G39V, R1030X, R7G, E24A, Q90X, A218V, A259V, W581X, G729R, R859W, c.-150T>C and c.*126G>C. Glucocorticoids were used in 14 patients, immunosuppressive agents in 13, and tocilizumab in 2. Seventeen patients had good responses to therapy. When compared with 50 NLRP12-AID patients from other countries, Chinese patients had fewer variants in exon 3, higher incidences of cutaneous rash, pharyngitis/tonsillitis and lymphadenopathy. Among all these 70 NLRP12-AID patients, patients carrying non-exon-3 variants had higher frequencies of ocular involvement, pharyngitis/tonsillitis, headache and lymphadenopathy than those with exon-3 variants.
    CONCLUSIONS: This is the largest cohort of NLRP12-AID in the world and seven novel variants of NLRP12 were identified. Chinese adult patients of NLRP12-AID had more non-specific symptoms such as pharyngitis/tonsillitis and lymphadenopathy when compared with patients from other countries, for which the less occurrence of exon-3 variants might be one possible reason.
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