Human papillomavirus (HPV) infection is a significant concern for women receiving anti-tumor necrosis factor alpha (anti-TNFα) therapy. However, comparative data on HPV prevalence in inflammatory bowel disease (IBD) patients versus those with rheumatoid arthritis (RA) receiving the same immunosuppressive treatment are limited. This study aimed to assess overall HPV positivity, the prevalence of high-risk HPV subtypes (HPV16/18), and cervical cytology findings in women with IBD and RA treated with anti-TNFα. It also sought to explore whether differences in sexual function may account for the observed variations. This cross-sectional study included 47 women with IBD and 39 women with RA who had been treated with anti-TNFα therapy for at least 6 months. All participants underwent HPV DNA testing and Papanicolaou (PAP) cytology. Sexual activity was evaluated using the Female Sexual Function Index (FSFI). Statistical analyses were performed using chi-squared tests and independent-sample t-tests. HPV positivity was significantly lower in IBD patients compared to those with RA (approximately 21% [10 out of 47] vs. 43% [17 out of 39]; p < 0.05). The detection of high-risk HPV16/18 subtypes was much less frequent in IBD patients (5% [2 out of 47]) than in RA patients (21% [8 out of 39]; p < 0.01). No significant differences were found in the rates of premalignant or malignant PAP abnormalities between the two groups (IBD: 6% vs. RA: 8%; p > 0.05). FSFI scores were significantly lower in women with IBD, indicating reduced sexual function and lower levels of sexual activity compared to those with RA (mean FSFI: 18.3 ± 5.1 vs. 22.9 ± 4.7; p < 0.01). The frequency of sexual intercourse showed a moderate inverse correlation with HPV detection (r = −0.41; p < 0.01). Women with IBD receiving anti-TNFα therapy demonstrated a significantly lower prevalence of HPV infection and fewer high-risk HPV16/18 subtypes compared to women with RA treated with the same biologic therapy. Cervical cytological abnormalities did not differ between the two groups. The lower levels of sexual activity in IBD patients, as reflected by reduced FSFI scores, may partially explain their decreased exposure to HPV. These findings highlight the importance of including sexual health assessments when evaluating HPV risk in women undergoing long-term immunosuppressive therapy. References: Ricci C, Scaldaferri F, Colombo F, Armuzzi A, Lopetuso LR, Leone S, Gasbarrini A, Scambia G, De Vincenzo RP. Prevalence of cervical HPV and attitude towards cervical screening in IBD patients under immunomodulatory treatment: a multidisciplinary management experience. Eur Rev Med Pharmacol Sci. 2020 Jan;24(2):564-570. Szydlarska D, Jakubowska A, Rydzewska G. Assessment of sexual dysfunction in patients with inflammatory bowel disease. Prz Gastroenterol. 2019;14(2):104-108. doi: 10.5114/pg.2019.85893. Waisberg MG, Ribeiro AC, Candido WM, Medeiros PB, Matsuzaki CN, Beldi MC, Tacla M, Caiaffa-Filho HH, Bonfa E, Silva CA. Human papillomavirus and chlamydia trachomatis infections in rheumatoid arthritis under anti-TNF therapy: an observational study. Rheumatol Int. 2015 Mar;35(3):459-63. Conflict of interest: Dr. Mitrovic, Milos: No conflict of interest Knezevic, Tamara: No conflict of interest Kalaba, Ana: No conflict of interest Odanovic, Olga: No conflict of interest Kralj, Djordje: No conflict of interest Markovic, Srdjan: No conflict of interest
Liver steatosis (LS) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), but the impact of advanced therapies on hepatic health is still unclear. This study aimed to evaluate the dynamics of LS following the initiation of advanced therapies, including anti-tumor necrosis factor (anti-TNF) agents, anti-integrin therapy, anti-interleukin-12/23 blockade, and Janus kinase inhibition in treatment-naïve IBD patients. In this prospective single-center cohort study, adults with IBD who were starting advanced therapy and had baseline LS—defined as an attenuation coefficient (ATT) of ≥ 0.63 dB/cm/MHz and alanine aminotransferase (ALT) levels >40 IU/L—were followed for 26 weeks. Shear-wave elastography and laboratory testing were conducted at baseline and at week 26. Endoscopic remission and trough concentrations of the therapies were assessed. Each patient served as their own control. The primary outcome was the change in ATT, while secondary outcomes included changes in ALT levels and the effects of remission and drug exposure. Out of 174 patients initiating advanced therapies, 68 (39%) had LS (49 with ulcerative colitis and 19 with Crohn’s disease). Anti-TNF agents significantly improved LS: infliximab reduced ATT from 0.76 to 0.73 dB/cm/MHz (p = 0.041) and ALT from 50.2 to 45.6 IU/L (p = 0.035), while adalimumab reduced ATT from 0.83 to 0.79 (p = 0.009) and ALT from 56.3 to 50.9 IU/L (p = 0.010). Vedolizumab did not show an overall effect (ATT changed from 0.80 to 0.79, p = 0.268), but patients with both adequate trough levels and endoscopic remission showed improvement (ATT changed from 0.79 to 0.77, p = 0.031). In contrast, non-responders experienced worsening (ATT changed from 0.81 to 0.84, p = 0.033). Ustekinumab (n = 14) exhibited a neutral effect, with no significant changes in ATT (0.80 to 0.82, p = 0.217) or ALT (49.8 to 50.3, p = 0.421), regardless of remission status. Tofacitinib (n = 9) was associated with an increase in ALT (44.8 to 59.7, p = 0.004) and a borderline increase in ATT (0.74 to 0.80, p = 0.051), suggesting progression of LS. Overall, the most favorable LS outcomes were observed in patients achieving both endoscopic remission and adequate drug exposure across treatment classes. Anti-TNF agents significantly improve LS in IBD, while vedolizumab benefits only those with both pharmacokinetic adequacy and endoscopic remission. Ustekinumab appears metabolically neutral, and tofacitinib may worsen LS. When selecting advanced therapy, hepatic comorbidities should be considered, and longer-term follow-up is needed to elucidate the hepatic impact of different therapeutic mechanisms. References: Papaefthymiou A, Potamianos S, Goulas A, Doulberis M, Kountouras J, Polyzos SA. Inflammatory bowel disease–associated fatty liver disease: the potential effect of advanced therapies. J Crohns Colitis. 2022;16(6):852–862. Fazel Y, Koenig AB, Sayiner M, Goodman ZD, Younossi ZM. Epidemiology and natural history of non-alcoholic fatty liver disease. Metabolism. 2016;65(8):1017–1025. Rodriguez-Duque JC, Calleja JL, Iruzubieta P, Hernández-Conde M, Rivas-Rivas C, Vera MI, et al. Increased risk of metabolic dysfunction–associated fatty liver disease and liver fibrosis in inflammatory bowel disease independent of classic metabolic risk factors. Clin Gastroenterol Hepatol. 2023;21(2):406–414.e7. Conflict of interest: Dr. Mitrovic, Milos: No conflict of interest Knezevic, Tamara: No conflict of interest Odanovic, Olga: No conflict of interest Andrej, Stupar: No conflict of interest Kalaba, Ana: No conflict of interest Kralj, Djordje: No conflict of interest Markovic, Srdjan: No conflict of interest
Ustekinumab (UST) targets the IL12/23 p40 subunit, and it is a valuable second-line therapeutic alternative in Crohn’s disease (CD) and ulcerative colitis (UC). The variability in treatment response underscores the need for early identification of predictors of remission, such as UST exposure. To describe UST trough concentrations in a realworld IBD cohort including those with fistulizing CD phenotype, and examine associations of post-induction trough levels with clinical remission at week 26. Retrospective study from a tertiary IBD center. Serum UST troughs were measured after IV induction (260, 390 or 520 mg) and during SC maintenance (90 mg every 8 or 12 weeks). Demographic, clinical and treatment data were collected. Descriptive, t-test/Mann–Whitney U test and logistic regression analysis were utilized. Fiftyfive patients received UST, while TDM data were available for 40 out of which 95% diagnosed with CD. Twelve CD patients (32%) had fistulizing disease. All, except one patient, were previously treated with another biologic, mainly anti-TNF (86.84%). In total, 22 post-induction and 30 UST levels during maintenance were available. Postinduction UST levels were significantly higher than those observed during maintenance (7.62 vs. 1.86 μg/mL, p < 0.001). Patients with fistulas showed a tendency toward lower levels. Clinical remission at week 26 was associated with higher postinduction UST levels (median 8.12 vs 4.62 μg/mL, p = 0.047). A higher UST trough concentration tended to be associated with greater likelihood of remission (OR = 2.41, 95% CI 0.13–2.22, p = 0.076). In this first Serbian realworld series, higher UST levels early after induction showed a positive trend with clinical remission at week 26. Fistulizing CD showed a tendency toward lower concentrations. Although these results are based on small cohort of patients, they support early UST TDM in dose optimization. Conflict of interest: Dr. Kralj, Djordje: No conflict of interest Paravina, Nikola: No conflict of interest Markovic, Srdjan: No conflict of interest Knezevic, Tamara: No conflict of interest Jovanovic, Marija: No conflict of interest Sreckovic, Slobodan: No conflict of interest Kalaba, Ana: No conflict of interest Vucicevic, Katarina: No conflict of interest
Introduction: Long COVID, also referred to as post-acute sequelae of SARSCoV-2 infection (PASC), is defined as a condition occurring after SARS-CoV-2 infection and characterized by the persistence of symptoms lasting at least three months. These symptoms may be continuous, intermittent, remitting, or progressive, and can affect one or multiple organ systems. It is particularly important in older adults due to higher morbidity, mortality, and the risk of functional and cognitive decline. Objective: To examine the prevalence and most common symptoms of long COVID in patients older than 65 years, as well as its impact on daily activities and social isolation. Methods: The study included 100 patients treated at the Geriatrics Department of the University Hospital “Zvezdara,” who had recovered from COVID-19. Data were collected through face-to-face interviews using a questionnaire covering system-specific symptoms, cognitive and psychological complaints, sleep disorders, and social isolation. Results: The mean age of participants was 73.9 ± 6.2 years, and 60% were women. The most common symptoms were fatigue (90%), memory impairment (63%), insomnia (61%), muscle pain (59%), depressive mood (54%), and chest pain (54%). Fatigue was the leading factor limiting daily activities (70%). Social isolation was reported by 65% of respondents, 78% stated that they were less physically active than before, while 44% continued to fear reinfection Conclusion: Long COVID is common in older patients and encompasses a wide range of symptoms that significantly affect daily life and contribute to social isolation. Early recognition and a multidisciplinary approach are essential for the adequate management of these patients.
