Mild elevation of liver function tests associated with renal cell carcinoma in a multimorbid older patient - a case of Stauffer's syndrome.

We describe a case of a 74-year-old patient with recurrent fever of up-to 38.5°C, nocturnal sweating, weight loss of 4 kg, non-characteristic pain, and elevation of liver function tests (LFTs), who was diagnosed with Stauffer's syndrome. The patient successfully underwent laparoscopic heminephrectomy. The histology was clear-cell carcinoma of the right kidney (cT1a). The abnormalities in laboratory tests, such as Erythrocyte Sedimentation Rate, C-reactive protein, LFTs, α2-globulin, and most clinical symptoms abated 2 weeks post-surgery. We hypothesize that elevated LFTs in renal cell carcinoma patients could help deciding in favour of surgery in cases where the initial decision would be watchful waiting.

The role of NPM1 alternative splicing in patients with chronic lymphocytic leukemia.

OBJECTIVES: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with heterogeneous clinical course. Recent studies revealed a link between NOTCH1 mutation and the overexpression of MYC and MYC-related genes involved in ribosome biogenesis and protein biosynthesis, such as nucleophosmin-1 (NPM1), in CLL cells. In the present study, we aim to evaluate the impact of the NOTCH1 mutation on the MYC and MYC induced NPM1 expression in CLL cells via quantification of their transcripts. METHODS: Using qRT-PCR, we analyzed the levels of MYC and three main NPM1 splice variants in 214 samples collected from CLL patients. We assessed the impact of each splice variant on CLL prognostic markers, including the IGHV, TP53, NOTCH1, SF3B1, and MYD88 mutational status, cytogenetic aberrations, and laboratory features. RESULTS: Significantly higher levels of NPM1.R1 transcripts in patients with unmutated compared to mutated IGHV status were found. The median time to first treatment (TTFT) in patients with a high level of NPM1.R1 was significantly shorter compared to the group with low NPM1.R1 levels (1.5 vs 33 months, p = 0.0002). Moreover, in Multivariate Cox Proportional Hazard Regression Model NPM1.R1 splice variant provided an independent prognostic value for TTFT. CONCLUSION: In conclusion, our study indicates the prognostic significance of the level of NPM1.R1 expression and suggests the importance of splicing alterations in the pathogenesis of CLL.

Disease burden in older Ukrainian refugees of war: a synthetic reanalysis of public records data.

BACKGROUND: Since the Russian invasion of Ukraine on Feb 24, 2022, more than 6 million Ukrainians, including hundreds of thousands of older people, have sought safety abroad. Older people generally have a higher burden of disease than younger people and the aim of our study was to estimate this burden in older Ukrainian refugees, given the potential financial and logistical impacts on the health-care systems of receiving countries. METHODS: On May 20, 2022, we searched the official websites of the Polish Ministry of Digitisation for data on Ukrainian refugees who had applied between Feb 24, 2022, and May 19, 2022 for a Polish personal identification number (PESEL). We extracted the number of older people (ie, of pension age, which in Ukraine is 60 years or older for men, and 55 years or older for women). We calculated the percentage of older people among these PESEL applicants then extrapolated this percentage to two groups, for which population data had been extracted from UN, WHO, and Polish Border Guards websites: refugees who had crossed into Poland but had not applied for a PESEL and refugees who had fled to neighbouring countries other than Poland. Between April 4 and May 19, 2022, we searched the Ukrainian Ministry of Health official website for data on the prevalence and incidence of various diseases in the Ukrainian population of older people. We asked the Ukrainian Ministry of Health to confirm and expand on the website data, and thereby obtained annual data for 2010-17. The ministry did not supply tuberculosis statistics, so on May 21, 2022, we searched the Ukrainian Ministry of Health website and extracted the most recent tuberculosis data, which were for 2020. We then calculated the absolute prevalence and incidence of diseases in older refugees. FINDINGS: As of May 19, 2022, 6·3 million Ukrainians had fled their country, including 3·5 million (56%) who had entered Poland. 1 114 418 people applied for a PESEL, including 109 985 older people (91 349 Ukrainian women aged 55 years or older and 18 636 Ukrainian men aged 60 or older). We estimated that the overall number of older Ukrainian refugees was 624 690. We estimated that these older refugees have a mean of 2·5 diseases each, the most frequent of which are cardiovascular diseases, followed by gastrointestinal, respiratory, musculoskeletal, and genitourinary diseases. We estimated that the expected absolute incidence is greatest for pulmonary disorders (71 689 diagnoses), followed by cardiovascular (49 327), ocular (24 100), musculoskeletal (20 367), and genitourinary (16 836) disorders. The estimated number of new diagnoses per year was 4578 for tuberculosis and 7827 for cancer. INTERPRETATION: Our data indicate that the disease burden of older Ukrainian refugees is considerable. Although our estimates are only approximations, they provide a basis for predicting which areas of health care will most need to be reinforced to meet the challenge of the potential financial and logistical impacts on receiving countries. FUNDING: There was no funding source for this study.

The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients.

Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84-1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment.

Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG).

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK- and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK- but not in MK+ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+.

Clonal evolution in CLL patients as detected by FISH versus chromosome banding analysis, and its clinical significance.

The acquisition of new aberrations during the course of chronic lymphocytic leukemia (CLL) named clonal evolution (CE) is usually detected by one of the two methods: chromosome banding analysis (CBA) and interphase fluorescence in situ hybridization (I-FISH). The purpose of this study was to compare the usefulness of FISH and CBA for detecting CE and to evaluate its influence on clinical outcome. FISH and CBA were performed at two time points: baseline and follow-up. Thirty-eight previously untreated patients with CLL were included in this study. CBA and I-FISH revealed CE in 15 (39.5%) and 10 (26.3%) patients, respectively. High-risk CE was detected in six cases by CBA and in five cases by I-FISH. In four cases with CE-dependent 17p abnormalities detected by CBA, metaphase FISH was needed for the confirmation of 17p13.1 deletion. Time from first-line to second-line treatment (TTST) and overall survival (OS) did not differ between patients with and without CE, irrespective of the CE-detecting method used. However, shorter OS (P = 0.043) and TTST (P = 0.006) were observed for the patients with potentially relevant CE (rCE) detected by CBA, in which acquired aberrations were present in at least 20% of undivided cells and/or changed baseline karyotype to abnormal or complex and were not resulting from 13q deletion. Our results suggest that some, but not all, CE-dependent aberrations detected by CBA influence clinical outcome. Moreover, I-FISH, which was aimed at detecting aberrations of prognostic significance, was found to be more precise than CBA in their detection, especially TP53 deletion.

Different prognosis of acute myeloid leukemia harboring monosomal karyotype with total or partial monosomies determined by FISH: retrospective PALG study.

A monosomal karyotype (MK) was identified by banding techniques (BT) in acute myeloid leukemia (AML). However, BT may be insufficient to determine the actual loss of a complete chromosome, especially in complex karyotypes. We have investigated the effect of monosomy type, total (MK-t) and partial (MK-p), reevaluated by FISH, on prognosis. We have found that complete remission rate and probability of overall survival at 1 year was higher in MK-p (n=27) than MK-t (n=15) group (40% vs. 15.4%, P=0.19 and 30% vs. 9%, P=0.046, respectively). Our results indicate for the first time that monosomy type influences the prognosis of MK-AML.