Autoimmune liver disease is classified into 3 well-defined entities: autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis, there is a group of patients who show ...characteristics of more than one entity and is called overlap syndrome (OS), according to the Paris criteria they are classified, the prevalence of overlap in our country is low. We describe the clinical and biochemical characteristics of patients with OS treated at the liver clinic at the Hospital General de México.
It is a retrospective and descriptive study, records of the autoimmune liver disease consultation were reviewed, searching for patients with OS using the Paris criteria in the period 2014-2023, descriptive statistics were performed with measures of central tendency and dispersion using SPSS 25.0.
22 patients were included, all of them with liver biopsy, 95% women aged 47 ± 12.6 years, the most common phenotype was PBC/HAI (59%). The time to diagnosis from initial manifestations ranged from 1 to 6 years, the most frequent tests were ANA (81%), AMA (63%), ASMA (18%) and LKM1 (18%), Immunoglobulin G levels on average 2048 ±643.8. The most frequent comorbidities were systemic sclerosis, arterial hypertension and hypothyroidism, the predominant symptoms were fatigue and pruritus reported in 36%; 90% were cirrhotic, Child Pugh A 70%, B 25% and C 5%. The most frequent decompensation was variceal hemorrhage (22.7%), 4.7% reported portal thrombosis, and 2 patients were transplanted.
Overlap syndromes are rare, we found the majority of patients are women with advancend stage of liver disease, the most frequent overlapping is PBC/HAI with a high proportion of positive serology tests and concordant biopsy, two patients underwent liver transplantation. It is important to always look for this rare syndrome.
Hepatic Encephalopathy (HE) is a common complication in patients with Chronic Liver Disease (CLD), and the development of this decompensation is multifactorial, including ammonia levels, inflammatory ...status, and sepsis, among others. A poorly studied factor in our population is the serum levels of 25-hydroxyvitamin D (25-OHD), which could act as a co-factor in HE. To assess if serum 25-hydroxyvitamin D (25-OHD) deficiency acts as a cofactor in the development of HE.
Observational, retrospective, analytical, case-control study; included subjects of both sexes, 18 years old and over, diagnosed with Chronic Liver Disease of different etiologies. Complete blood count, liver and kidney function, serum electrolytes, coagulation profile, and serum levels of 25-hydroxyvitamin D were recorded. They were evaluated using the West-Haven Criteria (WH).
Independent samples T-test was used to compare differences between 25-hydroxyvitamin D levels in patients with and without HE. The association between 25-OHD deficiency and HE was assessed using a chi-square test, with a significance level set at alpha=0.05. Out of a total of 96 patients, 36.5% had HE. The mean 25-OHD level in the HE group was 18.78 ± 8.56, compared to 22.77 ± 9.94 in the group without HE. The T-test was significant: T (1=2.072), p =0.041. Among patients with deficiency, 20/35 (57.1%) had EH, while 22/61 (36.1%) did not have HE. The chi-square test for the association between deficiency and HE was positive, with a value of (1)=4.015, p =0.045.
A causal relationship between 25-hydroxyvitamin D (25-OHD) deficiency and the development of HE cannot be attributed, as this is multifactorial. However, 25-OHD deficiency is common in patients with Chronic liver disease, and our study demonstrates that this deficiency acts as a cofactor, as there is a significant difference between the groups. It is necessary to validate these findings in the future through multivariate analysis to confirm our results.
Background: Reduced muscle strength (dynapenia) and mass (atrophy) are prognostic factors in oncology. Measuring maximal handgrip strength with dynamometers is feasible but limited by the cost of the ...reference device (JAMAR). Methods: A cross-sectional study was conducted on colorectal cancer outpatients treated with chemotherapy or under active surveillance in our center from September 2022 to July 2023. Accuracy, reliability, and concordance were compared for two handheld dynamometers: the JAMAR Plus (the gold-standard device) and the Camry EH101 (a low-cost index device). A simultaneous nutritional diagnosis with GLIM criteria and bioelectrical impedance analysis (BIA) was carried out. Results: A total of 134 participants were included. The median of maximal strength for the JAMAR Plus had a non-significant difference of 1.4 kg from the Camry EH101. The accuracy and reliability of the devices were high. Bland–Altman analysis showed a 0.8 kg bias and −4.1 to 5.6 kg limits of agreement (LoA); a 0.1 kg bias and −5.3 to 5.4 kg LoA in men; a 1.5 kg bias and −2.2 to 5.3 kg LoA in women. In total, 29.85% of the participants were malnourished. Prevalence of dynapenia increased from 3.67% with the JAMAR Plus to 5.14% with the Camry EH101. Both devices had a moderate and significant correlation with BIA-estimated muscle mass. Conclusions: The Camry EH101 was a cost-effective alternative to JAMAR Plus in our sample.
Lessons Learned
RAS‐ or BRAF‐mutated metastatic colorectal cancers (mCRCs) progressing after first‐line treatment have a poor prognosis.
European and U.S. guidelines include the multikinase inhibitor ...regorafenib as a standard option for second‐line therapy and beyond, based on the results of the randomized phase III CORRECT trial demonstrating improvement in survival.
Although stopped prematurely for failing to accrue, the PREVIUM trial, the first prospective interventional study exploring regorafenib as second‐line treatment for patients with mCRC bearing RAS or BRAF mutations, failed to demonstrate clinical activity in the population analyzed.
Background
Patients with RAS‐ or BRAF‐mutated (mut) metastatic colorectal cancer (mCRC) progressing on first‐line bevacizumab plus 5‐FU/irinotecan/oxaliplatin (FOLFOXIRI) have a poor prognosis. We aimed to assess the efficacy and safety of regorafenib in this population.
Methods
Regorafenib was administered daily for 3 weeks of each 4‐week cycle until disease progression or other reason. The primary endpoint was 6‐month progression‐free survival (PFS).
Results
KRAS, NRAS, or BRAF was mutated in mCRC samples in 60%, 20%, and 13% of patients, respectively. Median time from initial diagnosis of metastases to the start of regorafenib and treatment duration was 13.8 months and 7 weeks, respectively. Reasons for discontinuation included disease progression (80%), investigator decision (13%), and adverse events (AEs; 7%). Seven patients (47%) required dose reduction, mostly for asthenia (43%). The most common regorafenib‐related grade 3 AEs were asthenia (33%), dysphonia (13%), and hypertension (13%) (Table 1). There were no grade 4 toxicities. No patient was progression‐free at 6 months. Median PFS, time to progression (TTP), and overall survival (OS) were 2.2, 2.0, and 3.3 months, respectively.
Conclusion
Although stopped prematurely for failing to accrue, in the population analyzed, regorafenib failed to demonstrate clinical activity in KRAS‐ or BRAF‐mutated mCRC with progression following first‐line with FOLFOXIRI plus bevacizumab, although tolerability was acceptable. Our trial suggests that exploring regorafenib efficacy in an earlier line of therapy should not be undertaken without better population refinement.
经验获取
• 一线治疗后进展的 RAS 或 BRAF 基因突变转移性结直肠癌 (mCRC) 预后不良。
• 欧洲和美国的指南将多激酶抑制剂瑞格非尼作为二线治疗及后线治疗的标准选择,是根据随机III期CORRECT试验证实生存期改善的结果。
• 虽然因招募失败而提早结束,但PREVIUM 试验是首个前瞻性干预研究探索瑞格非尼作为二线治疗 RAS 或 BRAF 基因突变的 mCRC 患者,未能对分析人群取得临床活性。
摘要
背景。贝伐珠单抗 + 5‐FU/伊立替康/奥沙利铂 (FOLFOXIRI) 一线治疗后病情进展的 RAS 或 BRAF 基因突变 (mut) 转移性结直肠癌 (mCRC) 患者预后差。我们旨在评估瑞格非尼对该人群的有效性和安全性。
方法。瑞格非尼每天一次,连续给药 3 周,每 4 周为一个周期,直到患者病情出现进展或存在其他原因。主要终点是 6 个月无进展生存期 (PFS)。
结果。分别有 60%、20% 和 13% 的患者的 mCRC 样本出现 KRAS、NRAS 或 BRAF 基因突变。从转移的初始诊断到开始使用瑞格非尼和持续治疗的中位时间分别为 13.8 个月和 7 周。停药的原因包括病情进展 (80%)、研究者决定 (13%) 和不良事件 (AE;7%)。七名患者 (47%) 需要减少剂量,主要是因为身体虚弱 (43%)。最常见的瑞格非尼相关的 3 级 AE 是身体虚弱 (33%)、发声困难 (13%) 和高血压 (13%)(表 1)。未出现 4 级毒性。没有患者在 6 个月时病情无进展。中位PFS、至进展时间 (TTP) 和总生存期 (OS) 分别为 2.2、2.0 和 3.3 个月。
结论。虽然在招募失败的情况下提早结束,但在所分析的人群中,未证实瑞格非尼对 FOLFOXIRI + 贝伐珠单抗一线治疗后病情进展的 KRAS 或 BRAF 基因突变 mCRC 患者具有临床活性,尽管耐受性尚可。我们的试验表明,如果没有进行更好的人群细化,则不应在较早期的治疗中探索瑞格非尼的有效性。
Background
It is known that S‐pindolol attenuates muscle loss in animal models of cancer cachexia and sarcopenia. In cancer cachexia, it also significantly reduced mortality and improved cardiac ...function, which is strongly compromised in cachectic animals.
Methods
Here, we tested 3 mg/kg/day of S‐pindolol in two murine cancer cachexia models: pancreatic cancer cachexia (KPC) and Lewis lung carcinoma (LLC).
Results
Treatment of mice with 3 mg/kg/day of S‐pindolol in KPC or LLC cancer cachexia models significantly attenuated the loss of body weight, including lean mass and muscle weights, leading to improved grip strength compared with placebo‐treated mice. In the KPC model, treated mice lost less than half of the total weight lost by placebo (−0.9 ± 1.0 vs. −2.2 ± 1.4 g for S‐pindolol and placebo, respectively, P < 0.05) and around a third of the lean mass lost by tumour‐bearing controls (−0.4 ± 1.0 vs. −1.5 ± 1.5 g for S‐pindolol and placebo, respectively, P < 0.05), whereas loss of fat mass was similar. In the LLC model, the gastrocnemius weight was higher in sham (108 ± 16 mg) and S‐pindolol tumour‐bearing (94 ± 15 mg) mice than that in placebo (83 ± 12 mg), whereas the soleus weight was only significantly higher in the S‐pindolol‐treated group (7.9 ± 1.7 mg) than that in placebo (6.5 ± 0.9). Grip strength was significantly improved by S‐pindolol treatment (110.8 ± 16.2 vs. 93.9 ± 17.1 g for S‐pindolol and placebo, respectively). A higher grip strength was observed in all groups; whereas S‐pindolol‐treated mice improved by 32.7 ± 18.5 g, tumour‐bearing mice only show minimal improvements (7.3 ± 19.4 g, P < 0.01).
Conclusions
S‐pindolol is an important candidate for clinical development in the treatment of cancer cachexia that strongly attenuates loss of body weight and lean body mass. This was also seen in the weight of individual muscles and resulted in higher grip strength.
The poor fertility of ram semen stored chilled for long periods has encouraged the development of protocols designed to improve the kinetic vigour and cervical barrier-crossing capacity of sperm. The ...present work evaluated the effect of sperm selection with Sephadex filtration and the supplementation of 2% glycerol (GLY) to extenders based on ultra-heat-treated skimmed milk (UHT) or Tris-Tes-Glucose (TEST) on ram sperm kinetic parameters, plasma membrane integrity, acrosome integrity, mitochondrial function and fertilizing ability, over long chilling times. The results showed that for non-filtered semen, values for progressive sperm motility (%PSM), straight line velocity (VSL, μm/s) and the percentage of sperm with an intact plasma membrane/intact acrosome/a high mitochondrial function index (%IPIAHM) at all times up to 96 h of chilling were higher when the UHT extender (P < 0.01) was used compared to TEST extender irrespective of the presence of GLY. When semen was previously filtered with Sephadex, the addition of GLY to the UHT extender improved total motility (%TM), the %PSM and the VSL at 96 h compared to all other treatments (P < 0.01). The best results of all were obtained with non-filtered semen and UHT either with or without GLY. Heterologous IVF using zona-intact bovine oocytes was used to assess the fertilizing capacity of non-filtered fresh (FS0), chilled-for-24 h (CS24) or chilled-for-48 h (CS48) ram semen diluted in UHT extender (GLY-free). Heterologous IVF showed that ram sperm, either FS0, CS24 or CS48, were equally capable of penetrating zona pellucida intact bovine oocytes, leading to pronuclear formation and hybrid embryo cleavage (46.3 ± 3.2; 48.8 ± 3.2; and 43.3 ± 3.5, respectively). No differences were seen with respect to fresh sperm in terms of sperm binding, penetration, polyspermy, pronucleus formation or cleavage rates (P > 0.05). In conclusion, neither Sephadex filtration nor addition of glycerol provided extra benefits to ram sperm chilled up to 96 h. Chilled, non-filtered sperm extended with UHT without GLY showed better sperm functionality than did similar sperm extended with TEST extenders. Indeed, sperm diluted in UHT extender, maintained fertilizing ability up to 48 h.
•The Sephadex filtration and addition of 2% glycerol did not provide extra benefits to ram sperm chilled up to 96 h.•The use of skimmed milk UHT)-based extender improved motility parameters compared to Tris-Tes-Glucose (TEST)-based extenders under chilled conditions.•Fresh and cold-stored ram spermatozoa in UHT extender were capable to penetrate intact bovine oocytes leading to hybrid embryos.
Recurrent infective endocarditis (IE) is a major complication of patients surviving a first episode of IE. This study sought to analyse the current state of recurrent IE in a large contemporary ...cohort.
1335 consecutive episodes of IE were recruited prospectively in three tertiary care centres in Spain between 1996 and 2015. Episodes were categorised into group I (n=1227), first-IE episode and group II (n=108), recurrent IE (8.1%). After excluding six patients, due to lack of relevant data, group II was subdivided into IIa (n=87), reinfection (different microorganism), and IIb (n=15), relapse (same microorganism within 6 months of the initial episode).
The cumulative burden and incidence of recurrence was slightly lower in the second decade of the study (2006-2015) (7.17 vs 4.10 events/100 survivors and 7.51% vs 3.82, respectively). Patients with reinfections, compared with group I, were significantly younger, had a higher frequency of HIV infection, were more commonly intravenous drug users (IVDU) and prosthetic valve carriers, had less embolic complications and cardiac surgery, with similar in-hospital mortality. IVDU was found to be an independent predictor of reinfection (HR 3.92, 95% CI 1.86 to 8.28).In the relapse IE group, prosthetic valve endocarditis (PVE) and periannular complications were more common. Among patients treated medically, those with PVE had a higher relapse incidence (4.82% vs 0.43% in native valve IE, p=0.018).
and PVE were independent predictors of relapse (HR 3.14, 95% CI 1.11 to 8.86 and 3.19, 95% CI 1.13 to 9.00, respectively) and in-hospital-mortality was similar to group I. Three-year all-cause mortality was similar in recurrent episodes compared with single episodes.
Recurrent IE remains a frequent late complication. IVDU was associated with a fourfold increase in the risk of reinfection. PVE treated medically and infections caused by
increased the risk of relapse. In-hospital and long-term mortality was comparable among groups.
El presente estudio tiene como objetivo analizar los niveles de calidad de vida relacionada con la salud (CVRS) de los pacientes con enfermedad renal crónica avanzada (ERCA) en hemodiálisis y conocer ...las variables demográficas, médicas y psicológicas que se asocian con la CVRS y contribuyen a predecirla.
Estudio transversal con 302 pacientes con ERCA en tratamiento de hemodiálisis. Se evaluaron las siguientes variables: 1) CVRS (cuestionario Shorter Form Health Survey Questionnaire); 2) Ansiedad y depresión (Escala de ansiedad y depresión de Goldberg); 3) Datos sociodemográficos, y 4) Datos médicos. Se realizaron análisis correlacionales, comparación de medias y análisis de vías con variables latentes (PALV).
El PALV mostró que el 42% de la varianza en la CVRS podría explicarse por las variables evaluadas (χ2 / df=2,10; GFI=0,938; IFI=0,920; CFI=0,918; RMSEA=0,062; SRMR=0,056). La depresión fue el predictor más fuerte de la CVRS (-,71; p=0,002), seguida de la actividad física (-,19; p=0,044). La edad (-,122; p=0,034) y la comorbilidad (-,206; p=0,001) se asociaron débilmente con la CVRS física. La práctica de una actividad física regular está relacionado con la CVRS física (r=0,21; p=0,00) y mental (r=0,12; p=0,028).
Un alto porcentaje de la varianza en CVRS se explica por los niveles de depresión y actividad física. Las intervenciones para promover la CVRS en pacientes con ERCA deben centrarse en promover la actividad física y cuidar la salud mental del paciente.
The present study aims to analyze the levels of health-related quality of life (HRQL) in patients with end-stage kidney disease (ESKD) in haemodialysis, and to explore what demographic, medical and psychological variables are associated with HRQL and contribute to its prediction.
Cross-sectional study with 302 patients with advanced chronic kidney disease (ACKD) on haemodialysis. They were assessed: (1) HRQoL (Shorter Form Health Survey Questionnaire); (2) Anxiety and depression (Goldberg Anxiety and Depression Scale); (3) Sociodemographic data and (4) Medical data. Correlational analyses, means comparison and path analyses with latent variables (PALV) were conducted.
The PALV showed that 42% of the variance in the HRQL could be explained by the variables evaluated (χ2/df=2.10; GFI=.938; IFI=.920; CFI=.918; RMSEA=.062; SRMR=.056). Depression was the strongest predictor of HRQL (−.71; p=.002), followed by physical activity (−.19; p=.044). Age (−.122; p=.034) and comorbidity (−.206; p=.001) were weakly associated with physical HRQL. The practice of regular physical activity is related to the physical HRQoL (r=.21; p=.00) and mental (r=.12; p=.028).
A high percentage of the variance in HRQoL is explained by the levels of depression and physical activity. Interventions to promote HRQoL in patients with ESKD should focus in promoting physical activity and taking care of patient's mental health.
Un caso raro de mediastinitis necrosante descendente López-Frías López-Jurado, Alfonso; Pecharromán de las Heras, Inés; Pérez Templado Ladrón de Guevara, Josefa
Archivos de bronconeumología,
August 2019, Letnik:
55, Številka:
8
Journal Article
Marihuana como desencadenante de neumonitis en adolescentes López Gómez, Rebeca; Ladrón de Guevara, Ana Itziar; del Río Camacho, Genoveva
Anales de pediatría (Barcelona, Spain : 2003),
July 2023, 2023-07-00, Letnik:
99, Številka:
1
Journal Article
PDF
