The coronavirus disease 2019 pandemic had a major impact on most medical services. Our aim was to assess the outcome of acute cholecystitis during the nationwide lockdown period. All patients ...admitted to our emergency department for AC were analysed. Patient characteristics, performance status, AC severity, treatment modality and outcome of AC were assessed during the lockdown period (Period II: 1 April 2020-30 November 2021) and compared to a historical control period (Period I: 1 May 2017-31 December 2018). AC admissions increased by 72.8% in Period II. Patients were younger (70 vs. 74 years, p = 0.017) and greater in number in the CCI 1 group (20.4% vs. 11.2%, p = 0.043) in Period II. The unplanned readmission rate (6.3 vs. 0%, p = 0.004) and the gallbladder perforation (GP) rate was higher (18.0 vs. 7.3%, p = 0.006) in Period II. Percutaneous transhepatic gallbladder drainage (PTGBD) was more frequent (24.1 vs. 12.8%, p = 0.012) in Period II. In addition to a drop in patient age and CCI, a significant rise in the prevalence of acute cholecystitis, GP and unplanned readmissions was observed during the nationwide lockdown due to the COVID-19 pandemic. PTGBD was more frequent during this period, whereas successful conservative treatment was less frequent.
Background: Glycolysis inhibition is an active area of investigation in cancer. However, few compounds have progressed beyond the cell culture stage. We have recently demonstrated that genomic ...passenger deletion of the glycolytic enzyme Enolase 1 (EN01) leaves gliomas harboring such deletions with less than 10% of normal enzymatic activity, rendering them exquisitely sensitive to enolase inhibitors. Material and Methods: The compound that we employed for previous published in vitro studies, Phosphonoacetohydroxamate (PhAH), has very poor pharmacological properties and was ineffective in vivo. Here, we performed a SAR studies to increase inhibitor specificity towards ENO2 as well as pro-drugging to increase cell permeability. We tested the compound in vitro as well as in vivo to show the killing in ENO1-deleted tumor. Results: The lead compound generated by these efforts, termed POMHEX, is selectively active against ENOI-deleted glioma cells in culture at ∼35nM (versus 11M for PhAH). Using an orthotopic intracranial xenografted model where tumor growth and response to therapy are monitored by MRI, we show that POMHEX is capable of eradicating intracranial ENOI-deleted tumors, with mice remaining recurrence-free even after treatment discontinuation. Conclusions: Taken together, these results reinforce that glycolysis is a viable target and provide in vivo proof-of-principal for the concept of using passenger deletions as targetable vulnerabilities in cancer therapy.
Isolated extramedullary relapse (IEMR) of acute leukemia (AL) after allogeneic bone marrow transplantation (BMT) is a rare occurrence. It is seen more commonly after BMT than after conventional ...chemotherapy (CHT) alone. We describe the natural history and response to treatment in four patients with IEMR following allogeneic BMT. The results indicate a stronger graft-versus-leukemia (GVL) effect in the marrow than in the peripheral tissues (Fig. 4, Ref. 13). Full Text (Free, PDF) www.bmj.sk.
The results of treatment of acute promyelocytic leukemia, when combination ATRA + chemotherapy is used in induction and maintainance therapy and risk adapted strategy applied in consolidation, ...improved at present time. Enhanced supportive therapy also contribute to improved outcome of APL patients. 3 - year relapse free, overall survival and clinical and biological presenting features of APL patients were evaluated. Since January, 2001 till March, 2009, 32 patients treated with modified spanish treatment scheme were assessed. After june 2003 risk adapted strategy in protocol therapy according to spanish treatment group with ATRA and anthracyclines in consolidation therapy in high and intermediate risk patients was used. Cytoreduction therapy in patients with initially high leukocyte count was the modification of spanish treatment scheme. 29 (90.6%) patients achieved complete hematologic remission, 2 (6.3 %) molecular relapses were observed, death was observed in 4 patients (12.5%). The estimated 3-year OS was 90.6%; 95% CI (80.5%-100.0%), and estimated 3-year RFS was 95.5 %; 95 % CI (86.8%-100.0%). Survival results correspond with other published clinical studies. The number of relapses was slightly lower and the incidence of ATRA syndrome (50%) was higher when compare with the results of other study groups. Current recommendations for treatment with risk-adapted strategy for patients with newly diagnosed acute promyelocytic leukemia resulted in our patients group to comparable outcome and good compliance like in other published studies.
We describe the implementation, optimization, sensitivity determination and first clinical results of polymerase chain reaction (PCR) amplification of polymorphic short tandem repeat (STR) markers ...and Amelogenin locus coupled with fluorescent detection and capillary electrophoresis in chimerism monitoring of patients transplanted at three different transplant centers using a commercially available multiplex microsatellite assay. The chimerism analysis was performed with genomic DNA extracted from unselected peripheral blood leukocytes of one hundred pediatric and adult patients, who underwent allogeneic stem cell transplantation (SCT) from human leukocyte antigen (HLA) matched or one antigen mismatched related or unrelated donors for malignant (70 patients) and non-malignant (30 patients) diseases. Tested were 79 donor recipient pairs for 15 STR systems and identified an informative marker in all but one of them (98,7%), using 6 selected systems out of these fifteen, that appeared highly informative in our patients population. In 21 sex-mismatched donor recipient pairs we used the Amelogenin locus to distinguish the X and Y chromosome. In sixty-three out of these 100 patients chimerism was regularly analyzed from blood samples taken at various time points after SCT with the median follow up of 17 months. Complete chimerism (CC), maintained over the whole follow-up period, was detected in 24 (38, 1%), stable and decreasing mixed chimerism (MC) in 28 (44, 4%) and increasing MC in 11 patients (17, 5%). Patients with CC, stable and decreasing MC showed a significantly better (p 0,005) overall survival rate (0, 81), compared to those with increasing MC (0, 24). These results demonstrate that STR-based chimerism monitoring with sensitivity above 1% and high informativity (98, 7% of donor recipient pairs) is necessary in establishing the origin of engrafted cells after an allogeneic SCT, in detecting graft rejection and that it may contribute in identifying patients with imminent leukemia relapse.
An efficient synthesis of the cladiellin skeleton is reported utilizing methods that were previously developed in this laboratory. The approach is based on a SmI(2)-mediated cyclization reaction for ...the construction of the oxacyclononane unit. A 4 + 3 annulation strategy was used to create the octahydroisobenzofuran moiety. This route provides the cladiellin skeleton in only 14 steps without the use of protecting groups. The present approach also enabled the synthesis of the 3,7-diastereomer of the natural product polyanthellin A.
Arylglycines are biologically active α-amino acids. Our approach toward the synthesis of arylglycines features the Dötz benzannulation reaction between a variety of Fischer chromium carbene complexes
...3
and alkyne
4
derived from
l-serine. This leads to the formation of protected arylglycinols
5
, which can be transformed to the corresponding N-protected arylglycines.
Arylglycines are biologically active α-amino acids. Our approach toward the synthesis of arylglycines features the Dötz benzannulation reaction between a variety of Fischer chromium carbene complexes
3
and alkyne
4
. This leads to the formation of protected arylglycinols
5
, which can be transformed to the corresponding N-protected arylglycines.
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