Pralatrexate for Peripheral T-cell lymphoma (PTCL): Chance only supports the prepared mind. Systematic review.

BACKGROUND: Due to their primary effects on DNA synthesis, antimetabolites are most effective against actively dividing cells and significantly specific to the cell cycle phase. Pralatrexate (PDX), an antifolate metabolite designed to accumulate in cancer cells, was the first new agent approved by the US Food and Drug Administration for the treatment of resistant/recurrent peripheral T-cell lymphomas. PDX was a drug that is frequently used not only for PTCL, but also for cutaneous T-cell lymphoma (CTCL), extranodal natural killer (NK) / T-cell lymphoma. OBJECTIVE: This article reviews Pralatrexate's history, pharmacokinetics, clinical phase studies including phases I, II and III, types of cancers it is effective on, drug side effects, inhibition mechanism and even its use in the treatment of other cancers with innovative methods, including its antiviral effect against SARS-CoV-2 infection. METHODS: A comprehensive internet-based research was planned covering all published and unpublished studies on the subject. We conducted this review in accordance with Preferred Reporting Items for systematic reviews and meta-analysis (PRISMA-P), Cochrane Collaboration reporting items systematic reviews and meta-analysis. The results of the studies in the articles were recorded to include all phase studies. RESULTS: Pralatrexate was structurally designed to have enhanced cellular transport via RFC (reduced folate carrier type) and be subject to more polyglutamation compared to methotrexate. Enhanced polyglutamylating ability of pralatrexate is associated with increased tumor cell death and ultimately improved anticancer activity. Pralatrexate is considered as a promising drug for patients with recurrent and treatment-resistant PTCL with good survival advantage. At the same time, it is an antifolate agent which has a significant advantage over methotrexate as it does not cause myelosuppression. CONCLUSION: While there are manageable side effects such as thrombocytopenia, neutropenia, and mucositis, it is critical to explore new approaches, targeted agents, novel cellular therapies, and immunotherapies to determine optimal pretreatment in the rare but heterogeneous disease PTCL, and future studies and experienced haematologists are needed.

COVID-19 HASTALARINDA ANTÍFOSFOLÍPÍD ANTÍKOR (AFA) VARLIĞI

Objective: In our study, we aimed to show whether there is a relationship between antiphospholipid antibody (aPL) positivity and complications of COVID-19. Material and Methods: Eighty-three patients who were diagnosed with COVID-19 infection and hospitalized in the intensive care unit (ICU) of Bakirkoy Dr. Sadi Konuk Research and Training Hospital were included in our study as the case group and 79 healthy volunteers as the control group. Only patients with a positive Polymerase Chain Reaction (PCR) test were included in the case group. Serum antiphospholipid antibodies (aPL IgM/G), C-Reactive Protein (CRP), ferritin, procalcitonin (PCT), plasma D-Dimer levels, prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were analyzed by routine laboratory methods. Results: Both groups were found statistically similar in terms of gender (χ2 test, p=0.236). The mean age of the case group and control group was 60.54±16.86 and 51.47±14.64 years, respectively. When aPL positivity was evaluated between the case and control groups, a statistically remarkable difference was found between the groups (p=0.046). The case group showed an aPL positivity of 7.5% and the control group 1%. The correlation between D-Dimer, PT, INR, aPTT levels, and aPL IgM/G positivity in the case group was significant. Conclusion: Our results revealed that aPL positivity in patients with COVID-19 infection relate to the severity of the disease, in dependent from age and gender. To confirm the result of this study further studies with participation of larger patient groups from national and international hospitals are required. (English) [ FROM AUTHOR] Amaç: Çalışmamızda antifosfolipid antikor (AFA) pozitifliği ile COVID-19 komplikasyonları arasında bir ilişki olup olmadığını göstermeyi amaçladık. Gereç ve Yöntem: Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi yoğun bakım servisinde yatan COVID-19 enfeksiyonu tanısı almış 83 hasta olgu grubu olarak, 79 sağlıklı gönüllü de kontrol grubu olarak çalışmamıza dahil edildi. Olgu grubuna sadece Polimeraz Zincir Reaksiyon (PZR) test sonucu pozitif olan hastalar alındı. Serum antifosfolipid antikorları (AFA IgM/G), C-Reaktif Protein (CRP), ferritin, prokalsitonin (PCT) ve plazma D-Dimer seviyeleri, protrombin zamanı (PT) ve uluslararası normalleştirilmiş oran (INR), aktive parsiyel tromboplastin zamanı (aPTT), rutin laboratuvar yöntemleriyle analiz edildi. Bulgular: Her iki grup cinsiyet açısından istatistiksel olarak benzer bulundu (χ2 testi, p=0,236). Olgu grubu ve kontrol grubunun yaş ortalaması sırasıyla 60,54±16,86 ve 51,47±14,64 yıl idi. Olgu ve kontrol grupları arasında AFA pozitifliği değerlendirildiğinde, gruplar arasında istatistiksel olarak anlamlı fark bulundu (p=0,046). Olgu grubu %7,5 ve kontrol grubu %1 AFA pozitifliği gösterdi. Olgu grubunun D-Dimer, PT, INR, aPTT seviyeleri ile AFA IgM/G pozitifliği arasındaki korelasyon anlamlı bulundu. Sonuç: Sonuçlarımız, COVID-19 enfeksiyonu olan hastalarda AFA pozitifliğinin yaş ve cinsiyetten bağımsız olarak hastalığın şiddeti ile ilişkili olduğunu ortaya koydu. Bu çalışmanın sonucunu doğrulamak için ulusal ve uluslararası hastanelerden daha geniş hasta gruplarının katılımıyla daha ileri çalışmalara ihtiyaç vardır. (Turkish) [ FROM AUTHOR] Copyright of Istanbul Tip Fakültesi Dergisi is the property of Istanbul Tip Fakultesi Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

In-vitro cytokine production and nasopharyngeal microbiota composition in the early stage of COVID-19 infection.

BACKGROUND: To determine and compare nasopharyngeal microbiota (NM) composition, in vitro basal (Nil tube), provoked (Mitogen tube) production of cytokines at the early stage of COVID-19. METHODS: This cross-sectional study included 4 age and sex-matched study groups; group 1 (recovered COVID-19) (n = 26), group 2 (mild COVID-19) (n = 24), group 3 (severe COVID-19) (n = 25), and group 4 (healthy controls) (n = 25). The study parameters obtained from the COVID-19 (group 2, and 3) at the early phase of hospital admission. RESULTS: The results from the reaserch deoicted that the Mean ± SD age was 53.09 ± 14.51 years. Some of the in vitro cytokines production was significantly different between the study groups. Some of the findinggs on cytokines depicted a significant differences between study groups were interleukin (IL)-1ß Nil, IL-1ß Mitogen, and their subtraction (i.e Mitogen-Nil). Regarding IL-10, and IL-17a levels, Mitogen, and Mitogen-Nil tube production levels were significantly different between the groups. Surprisingly, most of these measures were lowest in the severe COVID-19 patients' group. Using discriminant analysis effect size (LEfSe), Taxa of NM with significant abundance was determined. About 20 taxa with an LDA score > 4 were identified as candidate biomarkers. Some of these taxa showed a significant correlation with IL-1ß and IL-10 Mitogen and Mitogen- Nil levels (R > 0.3 or < -0.3, p < 0.05). CONCLUSIONS: The findings of this perticular study regarting the early stage of COVID-19 showed that in vitro cytokines production, studies might be more useful than the ordinary cytokines' blood level measurement. Besides, the study identified some NM species that could be candidate biomarkers in managing this infection. However, further detailed studies are needed in these fields.

The effect of COVID-19 positivity on inflammatory parameters and thirty day mortality rates in patients over sixty five years of age with surgically treated intertrochanteric fractures.

PURPOSE: To evaluate the effect of COVID-19 positivity on inflammatory parameters and 30-day mortality rates in patients over 65 years of age who were operated on for intertrochanteric femur fractures (IFF). METHODS: Eighty-seven patients (31 males, 56 females) who had a dynamic hip screw (DHS) or proximal femur nail (PFN) for the IFF between March 2020 and November 2020 were included in the study. The patients were divided into two groups as COVID-19 confirmed and probable positive (Group 1) and COVID-19 negative (Group 2). Time to surgery, operation duration, length of hospital stay, 30-day mortality, rates of the intensive care unit (ICU) referral, and inflammatory parameters such as haemoglobin, CRP, sedimentation, PCT, D-Dimer, and ferritin were evaluated. RESULTS: No significant difference was observed in terms of demographic data such as age, gender, comorbidity, and fracture type between the groups. Thirty-day mortality, ICU referral rate, blood transfusion rate, and hospitalization period were higher in Group 1 (p = 0.016, p = 0.012, p = 0.031, and p = 0.011, respectively). The inflammatory parameters were higher in Group 1 compared to Group 2 in the preoperative and postoperative periods (p < 0.05). CONCLUSION: COVID-19 positivity increases inflammatory parameters (as expected) and increases the 30-day mortality and ICU requirement in patients with surgically treated IFF.