A case of late presentation of darunavir-related cholestatic hepatitis

2019 ◽  
Vol 30 (6) ◽  
pp. 620-622 ◽  
Author(s):  
Nina Yancheva ◽  
Radin Tzonev

We report a case of darunavir-induced cholestatic hepatitis in a human immunodeficiency virus (HIV)-infected patient in the third year of his combined antiretroviral therapy. During the patient’s monthly follow-up with regard to his HIV infection, elevated transaminase levels were detected. The patient was subsequently hospitalised at the AIDS and gastroenterology departments. All tested viral hepatitis markers were negative. A diagnosis of autoimmune hepatitis was also ruled out. The liver biopsy revealed cholestatic hepatitis. Darunavir withdrawal resulted in a progressive decrease in liver enzyme levels. We highlight the importance of recognising late development of liver injury secondary to the use of darunavir, and the importance of monitoring liver function in patients undergoing prolonged treatment involving darunavir.

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Pierangelo Chinello ◽  
Stefania Cicalini ◽  
Simona Pichini ◽  
Roberta Pacifici ◽  
Massimo Tempestilli ◽  
...  

Sildenafil and bosentan are increasingly used for the treatment of pulmonary arterial hypertension (PAH) in HIV-infected patients. However, concerns exist about pharmacokinetic interactions among sildenafil, bosentan and antiretroviral drugs, including protease inhibitors (PI). We describe here the case of an HIV-infected patient with PAH, who was co-administered bosentan 125 mg twice daily and sildenafil 40 mg three times per day, together with a ritonavir-boosted PI-based antiretroviral therapy; plasma levels of bosentan, sildenafil, N-desmethylsildenafil, and PI were measured. The patient had a sildenafil Cthrough and Cmax of 276.94 ng/mL and 1733.19 ng/mL, respectively. The Cthrough and the Cmax of bosentan were 1546.53 ng/mL and 3365.99 ng/mL, respectively. The patient was able to tolerate as high sildenafil blood concentrations as 10 times those usually requested and did not report any significant adverse reaction to sildenafil during the follow-up period. Therapeutic drug monitoring should be considered during sildenafil therapy in patients concomitantly treated with ritonavir-boosted PI.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 813
Author(s):  
Michele Manganelli ◽  
Ilaria Grossi ◽  
Manuela Ferracin ◽  
Paola Guerriero ◽  
Massimo Negrini ◽  
...  

Human hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver and the third cause of cancer-related deaths. The multikinase inhibitor sorafenib is a systemic drug for unresectable HCC. The identification of molecular biomarkers for the early diagnosis of HCC and responsiveness to treatment are needed. In this work, we performed an exploratory study to investigate the longitudinal levels of cell-free long ncRNA GAS5 and microRNAs miR-126-3p and -23b-3p in a cohort of 7 patients during the period of treatment with sorafenib. We used qPCR to measure the amounts of GAS5 and miR-126-3p and droplet digital PCR (ddPCR) to measure the levels of miR-23b-3p. Patients treated with sorafenib displayed variable levels of GAS5, miR-126-3p and miR-23b-3p at different time-points of follow-up. miR-23b-3p was further measured by ddPCR in 37 healthy individuals and 25 untreated HCC patients. The amount of miR-23b-3p in the plasma of untreated HCC patients was significantly downregulated if compared to healthy individuals. The ROC curve analysis underlined its diagnostic relevance. In conclusion, our results highlight a potential clinical significance of circulating miR-23b-3p and an exploratory observation on the longitudinal plasmatic levels of GAS5, miR-126-3p and miR-23b-3p during sorafenib treatment.


2021 ◽  
pp. 1-6
Author(s):  
Rabia Miray Kisla Ekinci ◽  
Sibel Balci ◽  
Haldun Dogan ◽  
Serdar Ceylaner ◽  
Celal Varan ◽  
...  

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome, caused by biallelic pathogenic mutations in the <i>PRG4</i> gene, is characterized by early-onset camptodactyly, noninflammatory arthropathy, coxa vara deformity, and rarely, pericardial effusion. Herein, we report 3 patients with CACP syndrome from 2 unrelated families. All patients are female, born to consanguineous parents, and had camptodactyly since the first years of their lives. Two patients had a prior diagnosis of juvenile idiopathic arthritis. Hip changes were present in 2 patients, and 2 of 3 patients had undergone surgery for camptodactyly. Routine echocardiographic evaluations were normal during the 2-year follow-up. This paper represents the third study including CACP patients from Turkey. Clinically, all 3 patients resembled juvenile idiopathic arthritis cases and received unnecessary medication. There is also an ongoing need for improving awareness of CACP and an effective treatment focusing on the lubrication of the joint space in CACP patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chinyere Ukamaka Onubogu ◽  
Ebelechuku Francesca Ugochukwu

Abstract Background A large number of HIV-infected children continue to die despite reported scale-up of paediatric HIV services. Aim The trend in attrition among children enrolled in an anti-retroviral therapy (ART) programme was evaluated. Methods This was a retrospective review of children enrolled into NAUTH ART programme between 2003 and 2019. Results 1114 children < 15 years at enrolment were studied. The male: female ratio was 1:1 while median age at enrolment was 4.3 years. About two-thirds had WHO stage 3 or 4 disease at enrolment. The rate of loss to follow-up (LTFU) and death were 41.0 and 8.4%, respectively, with overall attrition incidence of 108/1000PY. Despite the downward trend, spikes occurred among those enrolled in 2008 to 2011 and in 2017. The trend in 6-, 12-, 24- and 36-months attrition varied similarly with overall rates being 20.4, 27.7, 34.3 and 37.3%, respectively. Among those on ART, > 50% of attrition was recorded within 6 months of care. Advanced WHO stage, young age, non-initiation on ART or period of enrolment (P <  0.001), and caregiver (p = 0.026) were associated with attrition in bivariate analysis. Apart from caregiver category, these factors remained significant in multivariate analysis. Most LTFU could not be reached on phone. Among those contacted, common reasons for being lost to follow-up were financial constraints, caregiver loss, claim to divine healing, family disharmony/child custody issues and relocation of family/child. Conclusion/recommendation Attrition rate was high and was mostly due to LTFU. Predictors of attrition were late presentation, young age, delay in ART initiation and financial constraints. Efforts should be intensified at early diagnosis, linkage to care and implementation of “test and treat” strategy. Innovative child centered approaches should be adopted to enable the HIV-infected children remain in care despite challenges which can truncate treatment.


2021 ◽  
pp. 106689692098834
Author(s):  
Raquel Machado-Neves ◽  
Bernardo Teixeira ◽  
Elsa Fonseca ◽  
Pedro Valente ◽  
Joaquim Lindoro ◽  
...  

Most malignant tumors of the penis are squamous cell carcinomas (SCC), being divided in 2 groups, one human papillomavirus (HPV)-related and another non-HPV-related, with lymphoepithelioma-like carcinoma (LELC) being one of the rarest HPV-related SCC. In this article, we report a case of a 50-year-old man who presented testicular swelling and pain for the past 3 months. A penile mass was identified, and the patient was submitted to a total penectomy. The penectomy specimen showed an ulcerated lesion at the glans reaching the cavernous bodies. Microscopic examination showed undifferentiated epithelial cells with syncytial growth pattern mix with a dense lymphoplasmacytic infiltrate, consistent with LELC. The tumor cells expressed p16 and all 3 different clones of PDL1 (22C3, SP263, and SP142). The patient is alive and well with a follow-up of 3 months. To our knowledge, this is the third LELC of the penis reported in literature and the first case reported with PDL1 expression.


Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 835
Author(s):  
Mafalda N. S. Miranda ◽  
Marta Pingarilho ◽  
Victor Pimentel ◽  
Maria do Rosário O. Martins ◽  
Anne-Mieke Vandamme ◽  
...  

To control the Human Immunodeficiency Virus (HIV) pandemic, the World Health Organization (WHO) set the 90-90-90 target to be reached by 2020. One major threat to those goals is late presentation, which is defined as an individual presenting a TCD4+ count lower than 350 cells/mm3 or an AIDS-defining event. The present study aims to identify determinants of late presentation in Europe based on the EuResist database with HIV-1 infected patients followed-up between 1981 and 2019. Our study includes clinical and socio-demographic information from 89851 HIV-1 infected patients. Statistical analysis was performed using RStudio and SPSS and a Bayesian network was constructed with the WEKA software to analyze the association between all variables. Among 89,851 HIV-1 infected patients included in the analysis, the median age was 33 (IQR: 27.0–41.0) years and 74.4% were males. Of those, 28,889 patients (50.4%) were late presenters. Older patients (>56), heterosexuals, patients originated from Africa and patients presenting with log VL >4.1 had a higher probability of being late presenters (p < 0.001). Bayesian networks indicated VL, mode of transmission, age and recentness of infection as variables that were directly associated with LP. This study highlights the major determinants associated with late presentation in Europe. This study helps to direct prevention measures for this population.


Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 136
Author(s):  
Pavel Ryska ◽  
Jiri Jandura ◽  
Petr Hoffmann ◽  
Petr Dvorak ◽  
Blanka Klimova ◽  
...  

Background and objectives: For the treatment of chronic unilateral radicular syndrome, there are various methods including three minimally invasive computed tomography (CT)-guided methods, namely, pulsed radiofrequency (PRF), transforaminal oxygen ozone therapy (TFOOT), and transforaminal epidural steroid injection (TFESI). Despite this, it is still unclear which of these methods is the best in terms of pain reduction and disability improvement. Therefore, the purpose of this study was to evaluate the short and long-term effectiveness of these methods by measuring pain relief using the visual analogue scale (VAS) and improvement in disability (per the Oswestry disability index (ODI)) in patients with chronic unilateral radicular syndrome at L5 or S1 that do not respond to conservative treatment. Materials and Methods: After screening 692 patients, we enrolled 178 subjects, each of whom underwent one of the above CT-guided procedures. The PRF settings were as follows: pulse width = 20 ms, f = 2 Hz, U = 45 V, Z ˂ 500 Ω, and interval = 2 × 120 s. For TFOOT, an injection of 4–5 mL of an O2-O3 mixture (24 μg/mL) was administered. For the TFESI, 1 mL of a corticosteroid (betamethasone dipropionate), 3 mL of an anaesthetic (bupivacaine hydrochloride), and a 0.5 mL mixture of a non-ionic contrast agent (Iomeron 300) were administered. Pain intensity was assessed with a questionnaire. Results: The data from 178 patients (PRF, n = 57; TFOOT, n = 69; TFESI, n = 52) who submitted correctly completed questionnaires in the third month of the follow-up period were used for statistical analysis. The median pre-treatment visual analogue scale (VAS) score in all groups was six points. Immediately after treatment, the largest decrease in the median VAS score was observed in the TFESI group, with a score of 3.5 points (a decrease of 41.7%). In the PRF and TFOOT groups, the median VAS score decreased to 4 and 5 points (decreases of 33% and 16.7%, respectively). The difference in the early (immediately after) post-treatment VAS score between the TFESI and TFOOT groups was statistically significant (p = 0.0152). At the third and sixth months after treatment, the median VAS score was five points in all groups, without a statistically significant difference (p > 0.05). Additionally, there were no significant differences in the Oswestry disability index (ODI) values among the groups at any of the follow-up visits. Finally, there were no significant effects of age or body mass index (BMI) on both treatment outcomes (maximum absolute value of Spearman’s rank correlation coefficient = 0.193). Conclusions: Although the three methods are equally efficient in reducing pain over the entire follow-up, we observed that TFESI (a corticosteroid with a local anaesthetic) proved to be the most effective method for early post-treatment pain relief.


2020 ◽  
Vol 499 (3) ◽  
pp. 3738-3748
Author(s):  
R H Østensen ◽  
C S Jeffery ◽  
H Saio ◽  
J J Hermes ◽  
J H Telting ◽  
...  

ABSTRACT The Kepler spacecraft observed the hot subdwarf star PHL 417 during its extended K2 mission, and the high-precision photometric light curve reveals the presence of 17 pulsation modes with periods between 38 and 105 min. From follow-up ground-based spectroscopy, we find that the object has a relatively high temperature of 35 600 K, a surface gravity of $\log g / {\rm cm\, s^{-2}}\, =\, 5.75$ and a supersolar helium abundance. Remarkably, it also shows strong zirconium lines corresponding to an apparent +3.9 dex overabundance compared with the Sun. These properties clearly identify this object as the third member of the rare group of pulsating heavy-metal stars, the V366-Aquarii pulsators. These stars are intriguing in that the pulsations are inconsistent with the standard models for pulsations in hot subdwarfs, which predicts that they should display short-period pulsations rather than the observed longer periods. We perform a stability analysis of the pulsation modes based on data from two campaigns with K2. The highest amplitude mode is found to be stable with a period drift, $\dot{P}$, of less than 1.1 × 10−9 s s−1. This result rules out pulsations driven during the rapid stages of helium flash ignition.


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