The safety and efficacy of TNF inhibitors in patients with Behçet's disease: Retrospective study from eastern Turkey.

OBJECTIVE: We aimed to evaluate the clinical features, disease course, and associated factors for outcome in severe/refractory BD patients receiving TNF-i treatment. MATERIAL AND METHODS: This retrospective study was conducted by reviewing medical records from a tertiary referral center in Van province in Eastern Turkey. Data were obtained from patients' charts followed up between June 2019 and June 2022. RESULTS: We included 469 BD patients (59.3% male) whose 80 patients (17%) received TNF-i treatment in the study. The mean ± standard deviation of the patient age was 36.7 ± 10.1 years and the median (IQR) disease duration was 12 (12) years. IFX and ADAwere initiated in 67.5% (n = 54) and 32.5% (n = 26) patients, respectively. Overall and first-line retention rates of TNF-i were 84.7% and 92.6% for IFX and 83.3% and 80.8% for ADA, respectively. IFX was discontinued in 9 patients which were in 2 patients due to allergic reaction and tuberculosis, 3 patients for inefficacy, one patient for heart failure, and one patient for orbital zona. Although no serious adverse event was observed with ADA, 5 patients switched to IFX due to inefficacy. Overall, 72 patients (90%) resumed TNF-i at the end of the study; TNF-i was discontinued in 3 patients (3.8%) due to severe adverse events and in 5 patients (6.2%) with prolonged remission. CONCLUSION: In our study, no case of death was observed in TNF-i receiving patients. Most patients achieved attack-free and CS-free disease and retained TNF-i treatment. TNF inhibitors appear to be safe and effective in patients with severe/refractory Behçet's disease.

Comparative results of use and switching of anti-TNF-alpha agents in adult Behçet's uveitis.

PURPOSE: This study was planned to compare the clinical results and optical coherence tomography (OCT) data of patients who underwent adalimumab (ADA), infliximab (IFX) and switched protocols between these two methods in cases of Behçet's associated uveitis (BAU). METHODS: The patients with BAU who were treated with anti-TNF- α agents for at least one year were qualified for the chart review. The outcome parameters were the steroid-free remission state, the best-corrected visual acuity (BCVA), the central macular thickness (CMT), and the subfoveal choroidal thickness (SFCT) of the patients at the last visit. RESULTS: After a mean follow-up of 16.60 months, the rate of active inflammation decreased from 63.6% to 15.1%. Mean BCVA increased, mean CMT and mean SFCT decreased significantly at the last visit ( P < 0.001, P < 0.001, respectively). CONCLUSION: Anti-TNF- α treatment and switching protocols between these two agents effectively and safely control intraocular inflammation in BAU patients.

A novel spot mutation leading to sialidosis type 1-myoclonus syndrome and optical coherence tomography findings / Uma nova mutação pontual levando à sialidose tipo 1 - síndrome mioclônica e seus achados na tomografia de coerência óptica

ABSTRACT This report presents the optical coherence tomography findings and a new NEU1 mutation in bilateral macular cherry-red spot syndrome associated with sialidosis type 1. A 19-year-old patient with a macular cherry-red spot underwent metabolic and genetic analyses supported by spectral-domain optical coherence tomography. Fundus examination revealed bilateral macular cherry-red spot. Spectral-domain optical coherence tomography revealed increased hyperreflectivity in the retinal inner layers and the photoreceptor layer in the foveal region. The genetic analysis detected a new NEU1 mutation, which caused type I sialidosis. In cases with a macular cherry-red spot, sialidosis should be included in the differential diagnosis, and NEU1 mutation should be screened. Spectral-domain optical coherence tomography alone is not sufficient in the differential diagnosis because childhood metabolic diseases may exhibit similar signs.

RESUMO Neste artigo, objetivamos apresentar os achados da tomografia de coerência óptica em uma nova mutação detectada no gene NEU1 em um caso de síndrome macular vermelho-cereja bilateral associada à sialidose tipo 1. Um paciente de 19 anos com um achado de mancha macular vermelho-cereja foi submetido a análises metabólicas e genéticas, apoiadas por imagens de tomografia de coerência óptica de domínio espectral (SD-OCT). Ao exame de fundo de olho, foi observada uma mancha macular vermelho-cereja bilateral. Nas imagens de SD-OCT, observou-se hiper-refletividade nas camadas internas da retina e na camada fotorreceptora na região foveal. Foi realizada uma análise genética e uma nova mutação foi detectada no gene NEU1, resultando em sialidose tipo 1. Nos casos em que é detectada uma mancha vermelho-cereja na mácula, o diagnóstico diferencial de sialidose deve ser feito e mutações do gene NEU1 devem ser rastreadas. A SD-OCT por si só não é suficiente para o diagnóstico diferencial, porque achados de aparência semelhante podem se manifestar em casos de doenças metabólicas da infância.

Corneal parameters, ocular biometers, and retinal and choroidal thickness in acromegaly patients.

BACKGROUND: To compare ocular findings of acromegaly patients with healthy individuals and investigate the relation of serum levels of insulin-like growth factor (IGF-1) along with growth hormone (GH) and pituitary tumor (adenoma) dimensions (TD) with specific ocular parameters. METHODS: The ocular parameters of acromegaly patients (n = 38) were compared with those of healthy subjects (n = 36). These parameters were intraocular pressure, keratometric (K1-K2) values, central corneal thickness (CCT), total axial length along with anterior chamber-lens-vitreous length, retinal nerve fiber layer (RNFL) thickness, central foveal thickness (CFT), choroidal thickness (CT), ganglion cell layer thickness (GCLT), and inner plexiform layer thickness (IPLT). Also investigated was whether there was a correlation between disease duration, TD, GH, IGF-I, CCT, RNFL, CFT, GCLT, IPLT, and CT. RESULTS: The lens length of the acromegaly group was increased (p = 0.014). GH and IGF-1 levels were positively correlated with CT and CCT, respectively (p = 0.041, r = 0.343) (p = 0.03, r = 0.347). Analysis of TD also found a highly negative correlation with the mean RNFL thickness of the acromegaly patients (p < 0.01, r = -0.603). The mean value of the inner parts of GCLT and IPLT was negatively correlated with TD (p = 0.041, r = -0.343 and p = 0.025, r = -0.379, respectively). CONCLUSION: Serum IGF-1 and GH levels might be determinant factors in CCT and CT, respectively. The pituitary adenoma size increasing may be prone to lead RNFL, ganglion cell layer, inner plexiform layer thinning. Increased lens thickness was found in the acromegaly group.

Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm.

Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers. Recently, several clinical trials have utilized ICIs as potential neoadjuvant therapies for MSI-H gastrointestinal cancers and demonstrated deep clinical and pathological responses, creating opportunities for organ preservation. However, there are potential challenges to the neoadjuvant use of ICIs for certain disease types due to the clinical risk of overtreatment for a disease that can be cured through a surgery-only approach. In this review article, we discuss neoadjuvant management approaches with ICI therapy for patients with MSI-H gastrointestinal cancers, including those with oligometastatic disease. We also elaborate on potential challenges and opportunities for the neoadjuvant utilization of ICIs and provide further insight into the changing treatment paradigm of MMR-D/MSI-H gastrointestinal cancers.

The role of anterior segment optical coherence tomography in the evaluation of the pterygium.

BACKGROUND: To evaluate the ability of anterior segment optical coherence tomography (AS-OCT) to visualize the anatomic features of the pterygium and its invasion of the corneal layers. METHODS: Seventy-five eyes of 54 patients diagnosed with pterygium were included. All subjects underwent complete ophthalmologic examinations, including AS-OCT. The limbus-apex distance, vertical height at the limbus, invasion of the Bowman's and stromal layers, and other morphologic structures of the pterygium tissue were analyzed. RESULTS: The mean age of the patients was 49.67 ± 16.49 (20-85) years. The mean apex-limbus distance was 2548.37 ± 1026.32 (933-4597) µm, and the mean vertical height at the limbus was 4843.89 ± 1374.10 (1740-7784) µm. A space was observed beneath the pterygium tissue in 44 (58.67%) eyes. The mean width and height of this space were 1756.33 ± 560.22 (1009-3095) µm and 231.70 ± 85.88 (109-465) µm, respectively. Invasion of the Bowman's layer was apparent in 74 (98.67%) eyes, and invasion of the stromal layer was detected in 33 (44%) eyes. A hyperreflective layer was observed beneath the epithelial layer at the edge of the pterygium apex in 31 (41.33%) eyes. In 24 (92.31%) of the 26 advanced pterygium cases and 20 (40.82%) of the 49 early pterygium cases, a subpterygium space was found beneath the lesion (p = 0.0001). CONCLUSION: AS-OCT enables measurement of the actual size and thickness of pterygia, assessment of invasion of the Bowman's and stromal layers of the cornea, and evaluation of the pterygium structure. Over half of the eyes exhibited space beneath the pterygium.

Effects of Clinical and Tumor Characteristics on Survival in Patients with Hepatocellular Carcinoma with Bone Metastasis.

Background: Advanced hepatocellular carcinoma (HCC) generally has a dismal prognosis. Bone metastases from HCC are infrequent, with a poorer prognosis. However, the survival influencing factors are not yet well understood. Aim: The aim of the present study was to assess the clinical features and tumor characteristics of HCC patients with bone metastasis. Methods: A cohort of 170,576 adult patients with HCC was studied using the National Cancer Database (NCDB) spanning from 2010 to 2019, and within this group, 5285 patients (3.1%) were diagnosed with bone metastasis. We performed the Kaplan-Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics. Results: Of a total of 5285 HCC patients with bone metastasis, 86.2% were male and 61.2% were non-Hispanic white. Most patients (55.1%) were below 65, and 89% had a total Charlson-Deyo comorbidity score of under 3. Among patients with known tumor grade, 24.8% had well-differentiated tumors, and 36.1% had poorly differentiated tumors. Chemotherapy was administrated to 39.5% of patients. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 months vs 3.0 months, p = 0.001). Patients who received single or multiagent chemotherapy were significantly associated with improved OS compared to patients who did not receive chemotherapy (7.0 and 8.5 months vs 1.94 months, respectively). We also found mortality difference between age, comorbidity scores, facility types and race groups. Conclusion: In this cohort analysis of NCDB data, we found better OS in treatment receipt, lower tumor grade, younger age, non-Hispanic Black and Hispanic race, treatment at academic facility and lower comorbidity score in HCC patients with bone metastasis. The study results may have a consequential impact on the treatment decisions for HCC patients with bone metastasis.

A new perspective in the treatment follow-up of toxoplasma retinochoroiditis: Infiltrate thickness measurement.

BACKGROUND: This study aimed to describe the spectral domain optical coherence tomography (SD-OCT) findings of active lesions in toxoplasma retinochoroiditis cases and to examine the changes in retinochoroidal infiltrate thickness after treatment. METHODS: A total of 21 newly diagnosed patients with ocular toxoplasmosis were included in this prospective study. A complete ophthalmologic examination and SD-OCT were performed at the first visit. The patients were followed up weekly, and the SD-OCT images were taken over the lesion at each visit for 6 weeks. The characteristics of the active retinochoroiditis focus at the first visit were determined, and the infiltrate thicknesses at all visits were analyzed. RESULTS: A statistically significant BCVA difference was observed at the first visit and at the last visit 6 weeks later (p < 0.01). The first week after treatment showed a significant decrease in infiltrate thickness (113.904 ± 86.001 µm). In the following weeks, this decrease continued more softly. The thickness change at 6 weeks was significantly reduced (16.095 ± 14.784 µm) compared with the previous ones. Weekly infitrate thickness changes were compared among themselves; a statistically significant difference was found between the 1st and 2nd weeks and the 5th and 6th weeks (p = 0.035 and p = 0.007, respectively). Detached posterior vitreous in 71% (15/21) and increased posterior vitreous thickness in 76% (16/21) of active lesion were detected. All patients had 100% (21/21) increased retinal reflectivity and disorganized retinal layers, and choroidal hypo-reflectivity was observed in 86% (18/21). CONCLUSION: SD-OCT is a useful imaging modality in the diagnosis and follow-up of ocular toxoplasmosis cases. Serial thickness measurements of toxoplasma retinochoroiditis lesions may help confirm our diagnosis and determine the need for treatment.

The Role of HER2 Status in the Biliary Tract Cancers.

Despite recent advances, biliary tract cancer (BTC) is traditionally known as being hard to treat with a poor prognosis. Recent state-of-the-art genomic technologies such as next-generation sequencing (NGS) revolutionized cancer management and shed light on the genomic landscape of BTCs. There are ongoing clinical trials to assess the efficacy of HER2-blocking antibodies or drug conjugates in BTCs with HER2 amplifications. However, HER2 amplifications may not be the sole eligibility factor for these clinical trials. In this review, we aimed to comprehensively examine the role of somatic HER2 alterations and amplifications in patient stratification and provide an overview of the current state of ongoing clinical trials.

Comparison of both eyes anterior segment structures of patients with unilateral blunt trauma.

BACKGROUND: To evaluate anterior segment optical coherence tomography (AS-OCT) data in patients with unilateral blunt ocular trauma (BOT), to determine the relationship of results with hyphema development. METHODS: 21 patients who received unilateral BOT were included in the study. Healthy eyes of patients were included in the control group. Iris stromal thickness (IST), schlemm canal area (SCA) and pupil diameter were measured by AS-OCT of the participants. In addition, eyes with ocular trauma were divided into those with and without hyphema and compared in terms of these parameters. RESULTS: The mean nasal and temporal (n-t) IST was measured as 373± 40 µm and 369 ± 35 µm in BOT in comparison with 344 ± 35 µm and 335 ± 36 µm in control eyes, respectively (p = 0.000 and p = 0.001, respectively). The mean nasal and temporal (n-t) SCA was measured as 12,571 ± 880 µm2 and 12,162 ± 1181 µm2 in developed hyphema in comparison with 10,455 ± 1506 µm2 and 10,188 ± 939 µm2 in did not develop hyphema, respectively (p = 0.016 and p = 0.002 respectively). CONCLUSION: The ISTs of the traumatized eyes in the nasal and temporal quadrants were statistically thicker than the other healthy eyes. SCA in both nasal and temporal quadrants of eyes with hyphema was statistically significantly larger than the group without hyphema.

A novel spot mutation leading to sialidosis type 1-myoclonus syndrome and optical coherence tomography findings.

This report presents the optical coherence tomography findings and a new NEU1 mutation in bilateral macular cherry-red spot syndrome associated with sialidosis type 1. A 19-year-old patient with a macular cherry-red spot underwent metabolic and genetic analyses supported by spectral-domain optical coherence tomography. Fundus examination revealed bilateral macular cherry-red spot. Spectral-domain optical coherence tomography revealed increased hyperreflectivity in the retinal inner layers and the photoreceptor layer in the foveal region. The genetic analysis detected a new NEU1 mutation, which caused type I sialidosis. In cases with a macular cherry-red spot, sialidosis should be included in the differential diagnosis, and NEU1 mutation should be screened. Spectral-domain optical coherence tomography alone is not sufficient in the differential diagnosis because childhood metabolic diseases may exhibit similar signs.

Adoptive Cell Therapy in Hepatocellular Carcinoma: A Review of Clinical Trials.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Immune checkpoint inhibitors (ICIs) have become the new reference standard in first-line HCC treatment, replacing tyrosine kinase inhibitors (TKIs) such as sorafenib. Many clinical trials with different combinations are already in development to validate novel immunotherapies for the treatment of patients with HCC. Adoptive cell therapy (ACT), also known as cellular immunotherapy, with chimeric antigen receptors (CAR) or gene-modified T cells expressing novel T cell receptors (TCR) may represent a promising alternative approach to modify the immune system to recognize tumor cells with better clinical outcomes. In this review, we briefly discuss the overview of ACT as a promising treatment modality in HCC, along with recent updates of ongoing clinical trials.

The impact of adjuvant oxaliplatin and tumor sidedness on the overall survival of stage IIB colon cancer patients: a multicentre study.

The aim of this multicentre retrospective study was to compare the efficacy of adjuvant chemotherapy regimens both with and without oxaliplatin and tumor sidedness in stage IIB (pT4aN0) colon cancer patients. This study included patients with stage IIB colon cancer who underwent curative surgery and received adjuvant chemotherapy. The patients were divided into two groups (one with and one without oxaliplatin) to compare the overall survival (OS) in right- and left-sided tumors. The study population included 298 patients with stage IIB colon cancer (median age: 57) of whom 69.1% were male. Forty-four per cent of these patients (n = 131) were diagnosed with right-sided colon cancer. The median follow-up duration was 35.9 months. In the entire population, a median OS was not reached, and the five-year OS was 83%. The median disease-free survival (DFS) was 12 months. There was no significant difference in terms of the five-year OS between right- (82%) and left-sided (84%) colon tumors (p = 0.67). In addition, the five-year OS of patients treated with and without oxaliplatin were 76% and 89%, respectively, and there was no statistically significant difference (p = 0.23). The five-year OS of the patients treated with and without oxaliplatin were 83% and 96.5%, respectively, (p = 0.8) in right-sided colon tumors, while it was 75% and 93% (p = 0.06), respectively, in left-sided colon tumors. Tumor sidedness and the addition of oxaliplatin to adjuvant chemotherapy were not found to be associated with the OS in stage IIB colon cancer patients in our study. Further large prospective studies that also include MSI, RAS and BRAF status data are warranted in colon cancer patients.

Anti-tumor necrosis factor-alpha treatment in pediatric patients with pars planitis: a single-center experience from Turkey.

AIM: To evaluate the effectiveness and safety of anti-tumor necrosis factor-alpha (anti-TNF-alpha) treatment (Adalimumab [ADA]) combined with immunomodulatory agents (IMAs) in the treatment of pars planitis (PP). METHODS: The patients with PP who were treated with anti-TNF-alpha agents for at least six months were qualified for the chart review. The outcome parameters were the steroid-free remission state, the best-corrected visual acuity (BCVA) and the central macular thickness (CMT) of the patients at the last visit. RESULTS: After a mean total follow-up time of 15.5 ± 5.8 months (8-24 months), all the cases were in steroid-free remission at the last visit. The mean BCVA increased, and the mean CMT decreased significantly at the last visit (p < 0.001, p < 0.001, respectively). CONCLUSION: ADA combined with IMAs offers effective and safe treatment modalities in the control of chronic intraocular inflammation in PP cases.

Latent tuberculosis in adult hematopoietic stem cell transplantation recipients: Clinical experience from a previously endemic population.

Hematopoietic stem cell transplantation (HSCT) recipients may be at an elevated risk of developing active tuberculosis infection due to suppression in the cellular immune system. Herein, we aimed to evaluate the prevalence of latent tuberculosis and active tuberculosis in patients with allogeneic and autologous HSCT. In this cohort, data were obtained retrospectively from patients' records. The patients who were followed up in the bone marrow transplantation unit of the University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital between January 2016 and December 2019 were screened for the study. And the HSCT recipients who had tuberculin skin test and/or QuantiFERON-TB gold (QFT-GIT) test results were included in the study. A total of 361 patients were included in the study, 227 patients had autologous HSCT, and 134 patients had allogeneic HSCT. QFT-GIT was performed in 10 patients with allogeneic HSCT, and it was found positive in only 1 patient. Tuberculin skin test ≥5 mm was accepted as positive and was accepted to have latent tuberculosis, and it was positive in 18.2% (41) of the patients with autologous HSCT and was positive in 21.6% (29) of the patients with allogeneic HSCT. There was no significant difference between the 2 groups (P = .429). Isoniazid (INH) prophylaxis was started in 16.7% of patients with autologous HSCT and 22.4% of patients with allogeneic HSCT. During follow-up, active tuberculosis did not develop in any patients in both groups. There was no statistically significant difference found between allogeneic and autologous HSCT recipients regarding the prevalence of latent tuberculosis. Active tuberculosis infection did not develop in any of the patients who started INH prophylaxis. INH prophylaxis seems to be very efficient in preventing the reactivation of latent tuberculosis in patients going through allogeneic HSCT and/or autologous HSCT.

Corneal densitometry in patients with arcus senilis and its correlation with serum lipid levels.

Purpose: To evaluate corneal densitometry (CD) of patients with arcus senilis (AS) and its association with the serum lipid markers. Methods: This is a cross-sectional, case-control study. The AS diagnosis was made clinically. Forty-five eyes of 45 patients with AS and 38 eyes of 38 age-matched control subjects with no noticeable AS were enrolled in the study. All participants underwent detailed ophthalmologic examination along with corneal Scheimpflug imaging with CD measurement. The evaluated serum lipid markers of the participants included total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). The Spearman correlation analysis was used to correlate the serum lipid values and the CD. P < 0.05 was defined as statistically significant. Results: The male to female ratio was 26/19 and 14/24 in the study and control groups, respectively (P = 0.057). The mean age was 59.56 ± 8.7 and 56.47 ± 8.6 years in the study and control groups, respectively (P = 0.117). The mean total CD values in the zones extending from 2 to 12 mm were higher in the study group than in the control group (P < 0.001). The serum HDL level was found to be significantly decreased in the study group compared to the control group (P = 0.048 and Z = -1.976). There was a significant positive correlation between the serum triglyceride level and the CD value of the outermost zone (10-12 mm) (r = 0.334 and P = 0.025). Conclusion: The CD of patients with AS was found to increase not only in the peripheral zone but also in the cornea's paracentral zone compared to the healthy controls. The serum triglyceride level should give an insight into the intensity of arcus senilis. The serum HDL levels were decreased in patients with AS.

The impact of race and ethnicity on outcomes of patients with myelodysplastic syndromes: a population-based analysis.

Race and ethnic backgrounds affect the disease characteristics and clinical outcomes in many cancers, including acute myeloid leukemia; however, the association of race/ethnicity on myelodysplastic syndrome (MDS) is still controversial. Therefore, we aimed to study the impact of race/ethnicity on the disease characteristics and survival outcomes in patients with MDS. Adult patients with MDS diagnosed in 2004-2016 were selected using the SEER database. Race/ethnicity was categorized as non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic. Hispanic and NHB patients had significantly lower incidence rate ratio (IRR) in age group ≥01 years (p < .001) compared to NHW; however, in the age group <50 years, NHB patients had significantly higher IRR with an increased incidence rate of 49%. NHB patients had better overall survival than Hispanic and NHW patients (p < .001), even after adjusting for confounding variables. MDS have significant differences in age at diagnosis, disease risk, and survival outcomes based on racial/ethnic backgrounds.