Determination of the relationship of B7-H3, TİM-3, BTLA with immunohistochemical analysis, grade and lymph node involvement in noninvasive and invasive urothelial carcinomas of bladder

Mesane ürotelyal karsinomu en sık görülen 9. kanser tipidir. Yüzeyel mesane karsinomlarında 5 yıllık sağkalım %90'ın üzerindeyken kasa invaze mesane karsinomlarında bu oranın %45 ile %55 arasında bildirilmiştir. Bu durum immün kontrol noktalarını bloke eden antikorlar gibi yeni tedavi yöntemlerini araştırmaya yönlendirmiştir. İmmun kontrol noktaları bağışıklık tepkisinin tipini, büyüklüğünü, süresini düzenlemekle görevli hem uyarıcı hem de inhibe edici yollardan oluşur. BTLA, TİM-3 ve B7-H3 immun kontrol noktalarından olup T hücre ilişkili inhibitör reseptörlerdir. Çalışmamızda mesane ürotelyal karsinomlarında tümör hücrelerinde B7-H3, TIM-3 ve BTLA reseptörlerinin ekspresyon durumları ile bunların prognostik faktörlerle ilişkisini irdelemeyi ve neticede gelecekte bu moleküller üzerinden etki edecek ilaçların mesanenin ürotelyal karsinomlarında kullanımı ile ilgili ipucu elde edebilmeyi amaçladık. Çalışmamıza Meram Tp Fakültesi Patoloji Anabilim Dalında 2013-2018 yıllarında noninvaziv veya invaziv ürotelyal karsinom tanılı 90 adet vaka dahil edildi. 13 adet normal görünümlü mesane dokusu kontrol grubu olarak belirlendi. Tüm olgulara immünohistokimyasal yöntem ile BTLA, TİM-3 ve B7-H3 çalışıldı. İmmunhistokimyasal çalışmanın sonuçları prognostik faktörlerden yaş, cinsiyet, histolojik derece, invazyon derinliği, lenf nodu metastazı varlığı ile ilişkileri istatistiksel olarak karşılaştırıldı. 90 adet ürotelyal karsinom olgusunun 60 tanesinde (%67,4) BTLA ekspresyonu tespit edilirken, 11 tanesinde (%12,2) yüksek ekspresyonu mevcuttu. BTLA ekspresyonu ile yaş, cinsiyet, histolojik grade, invazyon derinliği ve lenf nodu metastazı varlığı arasında istatiksel olarak anlamlı fark saptanmadı. TİM-3 ekpresyonu ile ileri Tevre arasında anlamlı ilişki mevcutken (p=0,001) histolojik derece ve lenf nodu metastazı varlığı ile arasında istatiksel olarak anlamlı korelasyon saptanmadı. B7-H3 ekspresyonu ile histolojik grade ve ileri Tevre arasında anlamlı korelasyon saptanırken lenf nodu metastazı varlığı ile arasında anlamlı fark tespit edilmedi. 17 olguda primer tümör dokusunda ve metastatik lenf nodu dokusunda BTLA, TİM-3 ve B7-H3 ekpsresyonları arasında anlamlı fark saptanmadı. Çalışmamız literatürde mesanenin ürotelyal karsinomlarında tümör hücrelerinde BTLA ekspresyonunu immunhistokimyasal yöntemle gösteren ve B7-H3 ekspresyonu ile yüksek histolojik derece ve ileri Tevre korelasyonunu gösteren ilk araştırmadır.Urothelial carcinoma of the bladder is the 9th most prevalent type of cancer. Superficial bladder carcinomas are associated with a 90% five-year survival rate, however, this rate was reported to vary between 45% and 55% in cases of muscle invasive bladder carcinoma. This has promoted research on novel treatment methods such as antibodies that block the immune checkpoints. Immune checkpoints consist of stimulatory and inhibitory pathways that are tasked with regulating the type, strength, and duration of the immune response. The immune checkpoints BTLA, TIM-3, and B7-H3 are T-cell co-inhibitory receptors. This study aims to investigate the expression levels of B7-H3, TIM-3, and BTLA receptors in tumor cells and their relationship with prognostic factors in urothelial carcinoma of the bladder, and consequently, obtain clues about the future use of medications that would take effect through these molecules in the treatment of urothelial carcinomas. This study included 90 cases who were diagnosed with noninvasive or invasive urothelial carcinomas between 2013-2018 in the Pathology Department of Meram Faculty of Medicine. The control group was comprised of 13 bladder tissues with a normal appearance. All cases were tested for BTLA, TIM-3, B7-H3 using immunohistochemistry. The results of the immunohistochemical work-up was statistically compared to prognostic factors including age, sex, histological grade, depth of invasion, and the presence of lymph node metastasis. BTLA expression was detected in 60 (67.4%) of the 90 urothelial carcinoma cases and 11 of these (12.2%) showed high expression. BTLA expression was not statistically correlated with age, sex, histological grade, the depth of invasion, and the presence of lymph node metastasis. TIM-3 expression was significantly correlated with an advanced T-stage (p=0.001), however, it did not have a statistically significant correlation with histological grade and the presence of lymph node metastasis. B7-H3 expression was significantly correlated with histological grade and an advanced T-stage (p=0.001), however, it did not have a statistically significant correlation with the presence of lymph node metastasis. In 17 cases, levels of BTLA, TIM-3, and B7-H3 expression were not significantly different between the primary tumor tissue and the metastatic lymph node tissue. Our study is the first to demonstrate BTLA expression in tumor cells in urothelial carcinoma of the bladder using immunohistochemistry and show a correlation between B7-H3 expression and a high histological grade and T-stage.

Ocular Surface in Patients with Obstructive Sleep Apnea Syndrome: Evaluation of Clinical Parameters and Impression Cytology

MakaleWOS : 000901834600003PubMed ID : 36138005Purpose:To evaluate the effect of obstructive sleep apnea syndrome (OSAS) on the ocular surface and conjunctival cytology and the relationship between the findings and disease severity.Methods:One hundred six eyes of 106 patients (77 patients with OSAS and 29 control subjects) were included in the study. Twenty-three patients with an apnea-hypopnea index (AHI) of 5 to 15 were classified as mild OSAS (group 1), 27 patients with an AHI of 15 to 30 were classified as moderate OSAS (group 2), and 27 patients with an AHI >= 30 were classified as severe OSAS (group 3). The following tests were used to evaluate the ocular surface: tear break-up time (TBUT), Schirmer I test, ocular surface disease index (OSDI), and conjunctival impression cytology (CIC). The results obtained from the tests were analyzed and compared between the groups.Results:The mean value of the Schirmer I test was 15.03 +/- 10.16 (1-35) mm in the control group, whereas it was found as 13.39 +/- 8.80 (3-35) mm, 9.85 +/- 7.81 (1-30) mm, and 9.41 +/- 7.53 (2-35) mm in the mild, moderate, and severe OSAS groups, respectively, and the difference between the groups was significant (P=0.002). Although the mean TBUT score was 9.83 +/- 5.03 (3-23) seconds in the control group, it was 11.04 +/- 6.22 (3-20), 6.26 +/- 3.48 (1-16), and 5.44 +/- 3.09 (1-10) in the mild, moderate, and severe OSAS groups, respectively, and the difference between the groups was significant (P<0.001). Although the mean OSDI score was 12.76 +/- 14.84 (range, 0-41.65) in the control group, it was 11.52 +/- 12.95 (range, 0-44.40), 25.06 +/- 19.45 (range, 0-75), and 20.31 +/- 19.87 (range, 0-77.70) in the mild, moderate, and severe OSAS groups, respectively, and the difference between the groups was significant (P=0.015). Although the mean CIC stage was 0.47 +/- 0.60 (0-2) in the control group, it was 0.89 +/- 0.74 (0-2), 1.52 +/- 0.75 (0-3), and 1.83 +/- 0.69 (1-3) in the mild, moderate, and severe OSAS groups, respectively, and the difference between groups was significant (P<0.001).Conclusion:In addition to decreased tear production and TBUT, cytological changes including squamous metaplasia were detected between patients with OSAS and the control group.Necmettin Erbakan Üniversitesi Meram Tıp Fakültes

How does the ERAS protocol work in patients who underwent cesarean section? (HERMES study)

Objective To assess the effect of the enhanced recovery after surgery (ERAS) protocol for cesarean deliveries (CD) on postoperative outcomes. Methods This multicenter prospective cohort study was conducted in six different centers between September 2020 and March 2021 and involved women who underwent either planned or unplanned CD. The primary outcome was time to the first passage of flatus following CD. Secondary outcomes included postoperative pain score, postoperative complications, and patient satisfaction. The protocol included early postoperative oral intake of ice cream and coffee, multimodal analgesia, antiemetic medications, and early ambulation. Results A total of 448 patients were included. The median time to the first passage of flatus was 10 h in the Hermes group and 18 hours in the control group (P < 0.001). Postoperative visual analog scale scores were significantly higher in the control group. Patient satisfaction scores and the frequency of postoperative complications did not differ between the groups (P = 0.08, P = 0.604, respectively). Conclusions The ERAS protocol, including early serving of ice cream and coffee in the early postoperative period, enabled early discharge and a faster return of bowel function. Implementation of the ERAS protocol for patients who underwent planned and unplanned CD appeared to be safe and effective

Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure

Background Candida glabratais the third leading cause of candidaemia in Turkey; however, the data regarding antifungal resistance mechanisms and genotypic diversity in association with their clinical implication are limited. Objectives To assess genotypic diversity, antifungal susceptibility and mechanisms of drug resistance ofCglabratablood isolates and their association with patients' outcome in a retrospective multicentre study. Patients/Methods Isolates from 107 patients were identified by ITS sequencing and analysed by multilocus microsatellite typing, antifungal susceptibility testing, and sequencing ofPDR1andFKS1/2hotspots (HSs). Results Candida glabrataprevalence in Ege University Hospital was twofold higher in 2014-2019 than in 2005-2014. Six of the analysed isolates had fluconazole MICs >= 32 mu g/mL; of them, five harboured uniquePDR1mutations. Although echinocandin resistance was not detected, three isolates had mutations in HS1-Fks1 (S629T, n = 1) and HS1-Fks2 (S663P, n = 2); one of the latter was also fluconazole-resistant. All patients infected with isolates carrying HS-FKSmutations and/or demonstrating fluconazole MIC >= 32 mu g/mL (except one without clinical data) showed therapeutic failure (TF) with echinocandin and fluconazole; seven such isolates were collected in Ege (n = 4) and Gulhane (n = 3) hospitals and six detected recently. Among 34 identified genotypes, none were associated with mortality or enriched for fluconazole-resistant isolates. Conclusion Antifungal susceptibility testing should be supplemented with HS-FKSsequencing to predict TF for echinocandins, whereas fluconazole MIC >= 32 mu g/mL may predict TF. Recent emergence ofC glabrataisolates associated with antifungal TF warrants future comprehensive prospective studies in Turkey