OBJECTIVE: To map management of different types of ectopic pregnancies in the Czech Republic using a questionnaire-based study. METHODS: In 2023, a total of 95 obstetrics and gynecology departments across the Czech Republic were surveyed using an online questionnaire, which inquired about the management strategies for various types of ectopic pregnancies. The departments were categorized based on the number of hysterectomies performed annually. Differences in responses between large centers and other departments were statistically compared. RESULTS: A total of 45 departments of all sizes completed the questionnaire. Two-thirds of all departments always perform salpingectomy in cases of tubal pregnancy (78% of large, 58% of medium-sized, and 40% of small departments). Systemic methotrexate administration for the treatment of intact tubal pregnancy is used by one-fifth of departments (22% of large, 23% of medium-sized, and 0% of small departments). In cases of atypical ectopic pregnancy localization, methotrexate treatment is used by 33% of large, 42% of medium-sized, and 40% of small departments. A statistically significant difference was observed in the clearly preferred laparoscopic approach for surgical management of cesarean scar pregnancy in large centers compared to smaller departments (P = 0.036). No other statistically significant differences were observed between the departments in other parameters. CONCLUSION: In cases of intact tubal pregnancy, four-fifths of obstetric and gynecological departments perform laparoscopic salpingectomy, while only one-fifth utilize systemic methotrexate for treatment. On the other hand, methotrexate is used by one-third to two-fifths of departments of all sizes in cases of atypical ectopic pregnancy localization.

• Keywords
• Czech Republic, Methotrexate, cervical pregnancy, cesarean scar pregnancy, ectopic pregnancy, interstitial pregnancy, questionnaire study, salpingostomy,
• MeSH
• Abortifacient Agents, Nonsteroidal therapeutic use   MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Pregnancy, Ectopic * therapy   surgery   MeSH
• Surveys and Questionnaires MeSH
• Salpingectomy statistics & numerical data   MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Abortifacient Agents, Nonsteroidal MeSH
• Methotrexate MeSH

BACKGROUND: Efficacy of tumour necrosis factor inhibitors (TNFi) for peripheral arthritis in patients with psoriatic arthritis (PsA) has been established in randomized clinical trials that have used improvement in summated joint counts as an outcome. Whether joints at different anatomical locations might respond differentially to TNFi remains unknown. The aim of the study was to investigate potential variations in the responsiveness to a first tumour necrosis factor inhibitor (TNFi) among joints at distinct locations in patients with psoriatic arthritis (PsA) treated in routine clinical care. METHODS: Bionaive PsA patients from nine European countries were included in this observational cohort study if ≥ 1 joint was swollen at the initiation of a first TNFi as monotherapy or added to methotrexate. Only the 28-joint count was available without imaging data confirming the presence of synovitis. The primary outcome was time to first resolution of joint swelling at each joint level. Hazard ratios (HR) for resolution comparing different joint locations were estimated using interval-censored mixed-effects Cox proportional hazards models, including a random effect for country and patient, adjusted for age and sex. RESULTS: A total of 1729 patients with 8397 swollen joints at the start of TNFi were included. Considering the upper extremity, a higher rate of resolution of joint swelling (HR, 95% CI) was observed for the shoulder (1.65, 1.16-2.35) and elbow (1.90, 1.38-2.61), while a lower rate was found for the wrist (0.72, 0.62-0.83) compared to the joints of digit 3. Within fingers, and using the same reference, joint swelling resolved fastest in digit 4 (1.77, 1.49-2.11) and digit 5 (1.88, 1.53-2.31). A lower rate of resolution of joint swelling was found for the knee in comparison to the elbow, the corresponding joint on the upper limb (0.56, 0.40-0.78). CONCLUSION: The time to resolution of joint swelling upon treatment with TNFi in patients with PsA seems to depend on the localisation of the affected joints.

• MeSH
• Antirheumatic Agents * therapeutic use   MeSH
• Adult MeSH
• Tumor Necrosis Factor Inhibitors * therapeutic use   MeSH
• Joints * pathology   drug effects   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Arthritis, Psoriatic * drug therapy   pathology   MeSH
• Registries MeSH
• Aged MeSH
• Tumor Necrosis Factor-alpha * antagonists & inhibitors   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Geographicals
• Europe epidemiology   MeSH
• Names of Substances
• Antirheumatic Agents * MeSH
• Tumor Necrosis Factor Inhibitors * MeSH
• Methotrexate MeSH
• Tumor Necrosis Factor-alpha * MeSH

Patients with testicular lymphoma are at an increased risk of central nervous system (CNS) disease. Optimal strategy for CNS relapse prevention is unknown. We analyzed treatment strategies, cumulative incidence of CNS relapse and prognosis in 229 patients with diffuse large B-cell lymphoma (DLBCL) and testicular involvement: 157 primary testicular lymphomas (PTL) in clinical stages IE/IIE and 72 patients in advanced stages (T-DLBCL) IIIE/IV. Treatments for PTL vs. T-DLBCL included: rituximab-based chemotherapy (80.9% vs. 90.3%), orchiectomy (94.3% vs. 65.3%) and contralateral testicular irradiation (59.8% vs. 44.4%). Majority (84.3%) received CNS prophylaxis with similar rates of prophylactic methotrexate (intravenous 19.1% vs. 16.6%, intrathecal 40.8% vs. 40.4%, or both 24.2% vs. 27.8%) between PTL and T-DLBCL (p = 0.89). Median follow-up was 51.8 months. CNS relapses occurred in 14 (6.1%) of 63 relapsing patients. The 5-year cumulative incidence of CNS relapse in PTL was 4.5% and in T-DLBCL 12.1%. Median time to CNS relapse was 21.9 months. In univariate analyses, orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (HR = 0.11 [95% CI, 0-0.124], p = 0.001). Rituximab significantly reduced CNS relapse risk in T-DLBCL (HR = 0.1002, p = 0.0005). Median progression-free survival (PFS) and overall survival (OS) following CNS relapse was dismal in T-DLBCL compared to PTL (PFS 1.6 vs. 37.8 months, p = 0.04 and OS 2.3 vs. 37.8 months, p = 0.05). This study confirmed a favorable impact of rituximab in prevention of CNS relapse in T-DLBCL. Methotrexate prophylaxis did not alter CNS relapse risk. Prognosis of CNS relapse is particularly poor in T-DLBCL.

• Keywords
• CNS relapse, Diffuse large B-cell lymphoma, Orchiectomy, Rituximab, Testicular involvement,
• MeSH
• Lymphoma, Large B-Cell, Diffuse * therapy   mortality   pathology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Methotrexate administration & dosage   MeSH
• Young Adult MeSH
• Central Nervous System Neoplasms prevention & control   MeSH
• Follow-Up Studies MeSH
• Orchiectomy MeSH
• Prognosis MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Retrospective Studies MeSH
• Rituximab administration & dosage   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Testicular Neoplasms * therapy   mortality   pathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Methotrexate MeSH
• Rituximab MeSH

The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy. Key words: MDA, GSH, Caspase-3, p53, Oxidative stress, Apoptosis.

• MeSH
• Antioxidants pharmacology   MeSH
• Bicyclic Monoterpenes * pharmacology   MeSH
• Liver drug effects   pathology   metabolism   MeSH
• Rats MeSH
• Chemical and Drug Induced Liver Injury prevention & control   pathology   metabolism   MeSH
• Methotrexate * toxicity   MeSH
• Monoterpenes pharmacology   therapeutic use   MeSH
• Myocardium pathology   metabolism   MeSH
• Oxidative Stress drug effects   MeSH
• Rats, Sprague-Dawley * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• alpha-pinene MeSH Browser
• Antioxidants MeSH
• Bicyclic Monoterpenes * MeSH
• Methotrexate * MeSH
• Monoterpenes MeSH

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

• Keywords
• cN+, induction chemotherapy, pathology, survival, urinary bladder neoplasms,
• MeSH
• Cisplatin administration & dosage   MeSH
• Cystectomy * methods   MeSH
• Deoxycytidine analogs & derivatives   administration & dosage   MeSH
• Gemcitabine MeSH
• Induction Chemotherapy * MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymph Node Excision MeSH
• Lymphatic Metastasis * MeSH
• Lymph Nodes pathology   MeSH
• Methotrexate administration & dosage   MeSH
• Urinary Bladder Neoplasms * drug therapy   pathology   mortality   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cisplatin MeSH
• Deoxycytidine MeSH
• Gemcitabine MeSH
• Methotrexate MeSH

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses. The impact of additional intrathecal (IT) MTX on systemic toxicity in induction therapy is unknown. Between June 1st 2010 and February 28th 2017, a total of 6,136 ALL patients aged 1-17 years were enrolled onto the AIEOP-BFM ALL 2009 trial. The effect of three versus five doses of IT MTX during induction therapy on the incidence of severe infectious complications was analyzed. Among 4,706 patients treated with three IT MTX doses, 77 (1.6%) had a life-threatening infection during induction as compared to 59 of 1,350 (4.4%) patients treated with five doses (P<0.001; Odds Ratio 2.86 [95% Confidence Interval 1.99-4.13]). In a multivariate regression model, treatment with additional IT MTX proved to be the strongest risk factor for life-threatening infections (Odds Ratio 2.85 [1.96-4.14]). Fatal infections occurred in 16 (0.3%) and 38 (1.6%) patients treated with three or five IT MTX doses, respectively (P<0.001). As the relevance of additional intrathecal MTX in induction for relapse prevention in CNS2 patients is unclear, doses of intrathecal therapy have been reduced for these patients. (Clinicaltrials.gov identifiers: NCT01117441 and NCT00613457).

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * complications   drug therapy   MeSH
• Child MeSH
• Induction Chemotherapy adverse effects   MeSH
• Combined Modality Therapy MeSH
• Humans MeSH
• Methotrexate * therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Methotrexate * MeSH

PURPOSE: The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them. METHODS: We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment. RESULTS: Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options. CONCLUSION: No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.

• Keywords
• Bladder cancer, Chemotherapy, Cisplatin, Neoadjuvant, Radical cystectomy,
• MeSH
• Bayes Theorem MeSH
• Cisplatin * therapeutic use   MeSH
• Cystectomy MeSH
• Doxorubicin therapeutic use   MeSH
• Gemcitabine MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Urinary Bladder Neoplasms * drug therapy   MeSH
• Neoadjuvant Therapy methods   MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Network Meta-Analysis MeSH
• Vinblastine therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Cisplatin * MeSH
• Doxorubicin MeSH
• Gemcitabine MeSH
• Methotrexate MeSH
• Vinblastine MeSH

PURPOSE: The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated. PATIENTS AND METHODS: We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR. RESULTS: The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84). CONCLUSION: The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].

• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma * MeSH
• Child MeSH
• Infant MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma * drug therapy   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Risk Factors MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Methotrexate MeSH

PURPOSE: Most aspects of osteosarcoma have been addressed in detail, but there is no comprehensive analysis of deceased patients and causes of death. METHODS: The database of the Cooperative Osteosarcoma Study Group COSS (1980-03/31/2021; 4475 registered high-grade central osteosarcoma patients) was searched deaths from any cause. Affected patients were analyzed for demographic and baseline variables and disease-status at the time of demise. Deaths from causes other than osteosarcoma were analyzed in detail. RESULTS: A total of 1520 deceased patients were identified (median age (range) at osteosarcoma diagnosis 16 (2-78) years; 908 (59.7%) male, 612 (40.3%) female; primary tumor: extremities 1263 (83.1%), trunk 208 (13.7%), craniofacial 47 (3.1%) (site unknown 2); metastases at registration: absent 1.051 (69.1%), present 466 (30.7%) (3 no data). The median time from diagnosis to death was 2.22 (0.08-32.02) years. 1286 (84.6%) patients succumbed to osteosarcoma (370 without achieving complete remission, 488 first, 428 more than one recurrences), 146 (9.6%) to other, 88 (5.8%) to unknown causes. Chemotherapy-related infections (40), secondary malignancies (39), and perioperative complications (19) were among the most frequent potentially treatment-related causes, and high-dose methotrexate (19), doxorubicin (17), and ifosfamide (15) were the drugs most commonly held responsible. Patients with unknown causes of death had an unusually long median follow-up. CONCLUSION: The major cause of death of patients after osteosarcoma is this malignancy, mostly from one of its multiple relapses. However, almost 10% of fatalities are due to other documented causes. Some of these deaths may be preventable with the knowledge gained from comprehensive analyses such as this.

• Keywords
• Adolescent, Adult, Child, Osteosarcoma, Survival,
• MeSH
• Cisplatin therapeutic use   MeSH
• Doxorubicin therapeutic use   MeSH
• Ifosfamide therapeutic use   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Methotrexate MeSH
• Adolescent MeSH
• Bone Neoplasms * drug therapy   MeSH
• Osteosarcoma * drug therapy   MeSH
• Cause of Death MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cisplatin MeSH
• Doxorubicin MeSH
• Ifosfamide MeSH
• Methotrexate MeSH

Mucocutaneous mycotic infections are common complications in patients on IL-17 inhibitor therapy. We report a case of a 33-year-old male with severe psoriasis and psoriatic arthritis on secukinumab combined with methotrexate and prednisone with swelling, otorrhea, and pain of the right ear and external auditory canal. Due to progressive hypacusis, a surgical solution was chosen. Tissue samples taken during surgery revealed the presence of Aspergillus fumigatus. Aspergillosis should be suspected in prolonged otorrhea, especially in immunocompromised patients. Without intervention, the disease could be fatal.

• Keywords
• Aspergillosis, anti-IL-17, psoriasis, psoriatic arthritis, secukinumab,
• MeSH
• Aspergillosis * etiology   complications   MeSH
• Adult MeSH
• Adrenal Cortex Hormones MeSH
• Humans MeSH
• Methotrexate therapeutic use   MeSH
• Arthritis, Psoriatic * complications   drug therapy   MeSH
• Psoriasis * drug therapy   complications   MeSH
• Ear, Middle MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• Adrenal Cortex Hormones MeSH
• Methotrexate MeSH
• secukinumab MeSH Browser