LEUKEMIJA I TRUDNOĆA. NIJE DALJE ŠTETNA POVEZANOST?

Purpose. Even though there are no solid data regarding chemotherapy treated leukemia during pregnancy, the results based on short series reports show that the management of such condition can be safely achieved during the second and third trimester. We present three personal cases of pregnant women treated with cytostatic agents, two of them accidentally receiving complete chemotherapy during the entire pregnancy without malformative consequences. First case. A 19 yrs old woman diagnosed with chronic myeloid leukemia who conceived spontaneously and mistook the pregnancy signs for a relapse of the disease. During the pregnancy she continued the treatment, receiving until the fifth month an association of Hydroxyurea and alfa-interferon and afterwards switched to Imatinib until term. She presented at 38–39 weeks and delivered by cesarean section a little girl of 3510 g in a perfect state of health. The blood count of both mother and child were normal. Second case. A similar situation in a young woman with lymphoblastic acute leukemia under treatment with Vincristin, Methotrexat, Purinethol. She presented in advanced spontaneous labour at 33–34 weeks and delivered a little girl of 1700 g without malformative signs and normal blood count. Third case. A 17 years old girl who was diagnosed with acute myeloid leukemia at 29 weeks pregnancy. She received induction chemotherapy with Ara-C, due to the significant bone marrow infiltrate and disease induced disseminated intravascular coagulopathy. She presented premature uterine contractions at 32 weeks and delivered by cesarean section a premature boy of 1750g with Apgar score 8. The infant did not present any malformation (by clinical and ultrasound examination) and the blood count was normal. The studies have shown so far that in the case of chronic myeloid leukemia, the treatment with Imatinib was associated with 50% apparently normal live infants and that chemotherapy for acute leukemia during the second or third trimester may not require termination of pregnancy, because both remission and delivery of a normal infant are likely to be obtained.SAŽETAK. Cilj. Uopće nema čvrstih podataka o kemoterapijom liječenim leukemijama tijekom trudnoće. Rezultati na temelju kratkih izvješća pokazuju da liječenje tijekom drugog i trećeg tromjesečja može biti uspješno obavljeno. Prikazujemo tri trudnice liječene citostaticima, dvije od njih su bez posljedičnih malformacija primale kompletnu kemoterapiju tijekom cijele trudnoće. Prvi slučaj. Žena od 19 godina koja je spontano zanijela i krivo shvatila znakove trudnoće kao recidiv bolesti. Tijekom trudnoće je nastavila liječenjem, primivši do petog mjeseca smjesu hidroksiureje i -interferona i zatim do termina imatinib. Javila se s 38–39 tjedana trudnoće te je carskim rezom rodila savršeno zdravu malu djevojčicu težine 3510 grama. Krvna slika majke i djeteta je bila potpuno normalna. Drugi slučaj. Sličan slučaj mlade žene s limfoblastičnom akutnom leukemijom, liječenom vinkristinom, metotreksatom, purinetolom. Javila se u uznapredovalom porodu s 33–34 tjedana te je rodila djevojčicu tešku 1700 grama, bez malformacija i s normalnom krvnom slikom. Treći slučaj. Djevojka od 17 godina kojoj je s 29 tjedana trudnoće dijagnosticirana akutna mijeloična leukemija. Primila je indukcijsku kemoterapiju Ara-C-om, zbog značajne infiltracije koštane srži te bolešću uzrokovane diseminirane intravaskularne koagulopatije. S 32 tjedna počeli su trudovi te je carskim rezom rodila nedonošena dječačića težine 1750 grama s Apgar zbrojem 8. Dijete nije imalo malformacija ni klinički niti ultrazvučnim pregledom. Krvna slika je bila normalna. Do sada su studije pokazale da kronična mijeloična leukemija, liječena imatinibom, u 50% slučajeva rezultira rađanjem zdrava djeteta te da kemoterapija akutne leukemije tijekom drugog i trećeg tromjesečja trudnoće na zahtijeva prekid trudnoće, jer se može postići remisija bolesti i rađanje normalna djeteta

Lymphopenia: A predictive marker of disease severity in COVID-19 infection

Background. With the latest COVID-19 deaths reported to WHO now exceeding 3.3 million, COVID-19 has developed into a milestone of our medical generation, causing disruption in communities and hospital services. With complications raging from respiratory failure to inflammatory complication and even thrombotic events, we wanted to establish if lymphopenia is a predictive marker of disease severity in patients infected with SARS-CoV-2. Material and methods. 152 patients were included from 4 different departments of Colentina Clinical Hospital in this retrospective observational study beginning with July 2020 to March 2021. All of these patients were confirmed with COVID-19 by real-time reverse transcriptase polymerase chain reaction test for nasal and pharyngeal swab samples. As including criteria we have set the patients hospitalized confirmed with COVID-19, with at least 10 days of hospitalization. The data in demographic, basic clinical and laboratory characteristics and particular evolution was obtained from electronical medical records from each department involved in the study, by maintaining personal data confidentially. We set up criteria for lymphopenia as absolute lymphocyte count below 1.5 x 1000/µl, based on the laboratory reference values. The study group was divided into several groups: male and female, ICU (Intensive Care Unit) and non-ICU, deceased and released, lymphopenia at day 1 (day of admission to hospital) , lymphopenia at day 10 (10 days after hospital admission). Results. The age of the patients ranged from 17 to 92, with the median age of 57.62. Enrolled were 73 (47.4%) female patients and 79 (52.6%) male patients, with an ICU admission rate of 35.71% (55 patients), and a mortality rate of 21.43% (33 patients). Patients who have a severe form of COVID-19 and are admitted to the ICU for mechanical ventilation did not recover and died (p < 0.001). Male patients may have higher risk of requiring admission in ICU (p value = 0.357) and higher risk of death (p value = 0.241). Even in our small group of 152 patients, the elderly patients suffered a more severe form of the disease, which was reflected on the number of admission days (p = 0.07). In our specific population, based on the statistics, if we take the number of lymphocytes on the day of admission as the dependent factor, we can safely say that there is a statistically significant correlation between lymphopenia at day 1 and the ICU admission (p < 0.001) or death (p = 0.014). The number of lymphocytes following 10 days of admission is another prognostic marker as we can see from the results of statistic tests: there is a statistically significant correlation between lymphopenia at day 10 and the ICU admission (p < 0.001) or death (p < 0.001). Age is another predictive factor regarding the number of lymphocytes following 10 days of admission (r = -0.078 and p = 0.356). Conclusion. Lymphopenia is an easy-to-determine, efficient and reliable biomarker to establish the disease evolution in patients with COVID-19

LEUKEMIJA I TRUDNOĆA. NIJE DALJE ŠTETNA POVEZANOST?

Purpose. Even though there are no solid data regarding chemotherapy treated leukemia during pregnancy, the results based on short series reports show that the management of such condition can be safely achieved during the second and third trimester. We present three personal cases of pregnant women treated with cytostatic agents, two of them accidentally receiving complete chemotherapy during the entire pregnancy without malformative consequences. First case. A 19 yrs old woman diagnosed with chronic myeloid leukemia who conceived spontaneously and mistook the pregnancy signs for a relapse of the disease. During the pregnancy she continued the treatment, receiving until the fifth month an association of Hydroxyurea and alfa-interferon and afterwards switched to Imatinib until term. She presented at 38–39 weeks and delivered by cesarean section a little girl of 3510 g in a perfect state of health. The blood count of both mother and child were normal. Second case. A similar situation in a young woman with lymphoblastic acute leukemia under treatment with Vincristin, Methotrexat, Purinethol. She presented in advanced spontaneous labour at 33–34 weeks and delivered a little girl of 1700 g without malformative signs and normal blood count. Third case. A 17 years old girl who was diagnosed with acute myeloid leukemia at 29 weeks pregnancy. She received induction chemotherapy with Ara-C, due to the significant bone marrow infiltrate and disease induced disseminated intravascular coagulopathy. She presented premature uterine contractions at 32 weeks and delivered by cesarean section a premature boy of 1750g with Apgar score 8. The infant did not present any malformation (by clinical and ultrasound examination) and the blood count was normal. The studies have shown so far that in the case of chronic myeloid leukemia, the treatment with Imatinib was associated with 50% apparently normal live infants and that chemotherapy for acute leukemia during the second or third trimester may not require termination of pregnancy, because both remission and delivery of a normal infant are likely to be obtained.SAŽETAK. Cilj. Uopće nema čvrstih podataka o kemoterapijom liječenim leukemijama tijekom trudnoće. Rezultati na temelju kratkih izvješća pokazuju da liječenje tijekom drugog i trećeg tromjesečja može biti uspješno obavljeno. Prikazujemo tri trudnice liječene citostaticima, dvije od njih su bez posljedičnih malformacija primale kompletnu kemoterapiju tijekom cijele trudnoće. Prvi slučaj. Žena od 19 godina koja je spontano zanijela i krivo shvatila znakove trudnoće kao recidiv bolesti. Tijekom trudnoće je nastavila liječenjem, primivši do petog mjeseca smjesu hidroksiureje i -interferona i zatim do termina imatinib. Javila se s 38–39 tjedana trudnoće te je carskim rezom rodila savršeno zdravu malu djevojčicu težine 3510 grama. Krvna slika majke i djeteta je bila potpuno normalna. Drugi slučaj. Sličan slučaj mlade žene s limfoblastičnom akutnom leukemijom, liječenom vinkristinom, metotreksatom, purinetolom. Javila se u uznapredovalom porodu s 33–34 tjedana te je rodila djevojčicu tešku 1700 grama, bez malformacija i s normalnom krvnom slikom. Treći slučaj. Djevojka od 17 godina kojoj je s 29 tjedana trudnoće dijagnosticirana akutna mijeloična leukemija. Primila je indukcijsku kemoterapiju Ara-C-om, zbog značajne infiltracije koštane srži te bolešću uzrokovane diseminirane intravaskularne koagulopatije. S 32 tjedna počeli su trudovi te je carskim rezom rodila nedonošena dječačića težine 1750 grama s Apgar zbrojem 8. Dijete nije imalo malformacija ni klinički niti ultrazvučnim pregledom. Krvna slika je bila normalna. Do sada su studije pokazale da kronična mijeloična leukemija, liječena imatinibom, u 50% slučajeva rezultira rađanjem zdrava djeteta te da kemoterapija akutne leukemije tijekom drugog i trećeg tromjesečja trudnoće na zahtijeva prekid trudnoće, jer se može postići remisija bolesti i rađanje normalna djeteta

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR?=?1.022, 95%CI 1.007?1.038 and OR?=?1.025, 95%CI 1.001?1.051, respectively), while thromboprophylaxis use was protective (OR?=?0.199, 95%CI 0.061?0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR?=?1.062, 95%CI 1.017-1.109 and OR?=?2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration

COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41–0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02–1.04; HR = 1.79, 95% CI:1.04–3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated

The evolving landscape of COVID‐19 and post‐COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis