Psoriasis vulgaris (PV) is an inflammatory skin disease largely driven by aberrant αβT cells. Mucosal-associated invariant T (MAIT) cells, which constitute the largest circulating innate-like αβT ...cell community in human adults, are characterized by a semi-invariant TCRVα7.2 receptor and MR1-restricted affinity toward microbial metabolites. Limited MAIT TCRα diversity is complemented by a more variable TCRβ repertoire, but its footprint in the MAIT repertoire of PV patients has never been tested. Here, we used bulk TCRSeq, MiXCR, VDJTools, and Immunarch pipelines to decipher and compare TCRβ clonotypes from flow-sorted, peripheral TCRVα7.2
MR1-5-OP-RU-tet
MAIT cells from 10 PV patients and 10 healthy, matched controls. The resulting TCRβ collections were highly private and individually unique, with small public clonotype content and high CDR3β amino acid length variability in both groups. The age-related increase in the 'hyperexpanded' clonotype compartment was observed in PV, but not in healthy MAIT repertoires. The TCRβ repertoires of PV patients were also marked by skewed TRBV/TRBJ pairing, and the emergence of PV-specific, public CDR3β peptide sequences closely matching the published CDR3β record from psoriatic skin. Overall, our study provides preliminary insight into the peripheral MAIT TCRβ repertoire in psoriasis and warrants further evaluation of its diagnostic and clinical significance.
To determine the prognostic value of baseline red blood cell distribution width (RDW) in diffuse large B cell lymphoma (DLBCL) patients.
Data from 81 DLBCL patients diagnosed from 2006 to 2013 at the ...University Hospital Center Osijek, Osijek, Croatia, were reviewed. We evaluated disease outcome, overall survival (OS) and event-free survival (EFS), and demographic, clinical and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used.
Median age of patients was 64 years, 29 were men (35.8%). Higher RDW levels (%) were found in patients with advanced Ann Arbor clinical stage (14.94±1.82 vs 13.55±1.54, P=0.001) and in those with poor response to therapy (14.94±1.82 vs 13.55±1.54, P=0.001). Patients with RDW>15% (cut-off was calculated by receiver operating characteristics) had significantly worse OS (median range, 33 months 20-46 vs 74 months 65-82, P<0.001) and EFS (27 months 15-40 vs 68 months 59-77, P<0.001). Cox regression analysis showed that RDW>15% was an independent prognostic factor for OS (HR 3.654, 95% CI 1.128-11.836) and EFS (HR 2.611, 95% CI 1.012-6-739).
High baseline RDW is an independent prognostic marker of poor outcome in patients with DLBCL. RDW could be an easily available and inexpensive marker for the risk stratification in patients with DLBCL.
•Pulmonary embolism (PE) is infrequent in MPN patients.•Presentation and outcomes of PE in MPNs are similar to non-MPN PE patients.•sPESI is not prognostic in MPNs.
Background
Physical frailty and cognitive decline are two major consequences of aging and are often in older individuals, especially in those with multimorbidity. These two disorders are known to ...usually coexist with each other, increasing the risk of each disorder for poor health outcomes. Mental health disorders, anxiety and depression, are common in older people with multimorbidity, in particular those with functional or sensory deficits, and frailty.
Purpose
The aim of this study was to show how physical frailty, cognitive impairments and mental disorders, cluster in the real life setting of older primary care (PC) patients, and how these clusters relate to age, comorbidities, stressful events, and coping strategies. Knowing that, could improve risk stratification of older individuals and guide the action plans.
Methods
Participants were older individuals (≥60,
N
= 263), attenders of PC, independent of care of others, and not suffering from dementia. For screening participants on physical frailty, cognitive impairment, and mental disorders, we used Fried‘s phenotype model, the Mini-Mental State Examination (MMSE), the Geriatric Anxiety Scale (GAS), and the Geriatric Depression Scale (GDS). For testing participants on coping styles, we used the 14-scale Brief-Coping with Problems Experienced (Brief-COPE) questionnaire. To identify clusters, we used the algorithm
fuzzy k-means
. To further describe the clusters, we examined differences in age, gender, number of chronic diseases and medications prescribed, some diagnoses of chronic diseases, the number of life events, body mass index, renal function, expressed as the glomerular filtration rate, and coping styles.
Results
The most appropriate cluster solution was the one with three clusters, that were termed as: functional (FUN;
N
= 139), with predominant frailty or dysfunctional (DFUN;
N
= 81), and with predominant cognitive impairments or cognitively impaired (COG-IMP;
N
= 43). Participants in two pathologic clusters, DFUN and COG-IMP, were in average older and had more somatic diseases, compared to participants in cluster FUN. Significant differences between the clusters were found in diagnoses of osteoporosis, osteoarthritis, anxiety/depression, cerebrovascular disease, and periphery artery disease. Participants in cluster FUN expressed mostly positive reframing coping style. Participants in two pathological clusters were represented with negative coping strategies. Religion and self-blame were coping mechanisms specific only for cluster DFUN; self-distraction only for cluster COG-IMP; and these two latter clusters shared the mechanisms of behavioral disengagement and denial.
Conclusion
The research approach presented in this study may help PC providers in risk stratification of older individuals and in getting insights into behavioral and coping strategies of patients with similar comorbidity patterns and functional disorders, which may guide them in preparing prevention and care plans. By providing some insights into the common mechanisms and pathways of clustering frailty, cognitive impairments and mental disorders, this research approach is useful for creating new hypotheses and in accelerating geriatric research.
Summary
Background
The prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is associated with short-term and long-term outcomes of various malignancies. ...The prognostic value of PNI in diffuse large B cell lymphoma (DLBCL) remains unknown. The aim of the present study was to determine the prognostic value of baseline PNI in DLBCL patients.
Methods
We retrospectively analyzed data from 103 DLBCL patients treated with R‑CHOP or R‑CHOP-like regimens. We evaluated the significance of PNI as a predictor of response to treatment, overall survival (OS) and event-free survival (EFS).
Results
Patients with a PNI ≤ 44.55, where the cut-off was calculated by receiver operating characteristics (Youden index) and the same was obtained for response to treatment with 76.2 % sensitivity and a specificity of 85.4 %, for OS with 72.4 % sensitivity and a specificity of 90.5 % and for EFS with 65.6 % sensitivity and a specificity of 90.1 %, had significantly worse 5‑year OS (18.3 % vs 86.4 %,
P
< 0.001, log rank test) and 5‑year EFS (15.1 % vs 82.3 %,
P
< 0.001, log rank test). Regression analysis showed that PNI ≤ 44.55 was an independent prognostic factor for response to treatment with an odds ratio (OR) of 4.88 for treatment failure, 95 % confidence interval (CI) 1.077–22.105, OS hazard ratio (HR) 4.24, 95 % CI 1.451–12.392 and EFS HR 4.007, 95 % CI 1.48–10.852. Lower PNI levels were found in patients with advanced Ann Arbor clinical stage (46.6 ± 7.77 vs. 52.7 ± 5.43) and in those with poor response to therapy (40.58 ± 7.26 vs. 50.67 ± 6.26).
Conclusions
The PNI is a simple and useful marker to predict long-term survival outcome in DLBCL patients. Low PNI predicted poor outcome. A limitation of the study is its retrospective design in which the prognostic value was tested in the derivation cohort only. Notwithstanding, this is the first study suggesting that PNI is an important prognostic factor in DLBCL.
Objectives: The aim of this study was to examine the impact of the pentraxin 3 (PTX3) serum level and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on the severity of ...radiographic pulmonary infiltrates and the clinical outcomes of COVID-19. Methods: The severity of COVID-19 pulmonary infiltrates was evaluated within a week of admission by analyzing chest X-rays (CXR) using the modified Brixia (MBrixa) scoring system. The insertion (I)/deletion (D) polymorphism of the ACE gene and the serum levels of PTX3 were determined for all patients included in the study. Results: This study included 80 patients. Using a cut-off serum level of PTX3 ≥ 2.765 ng/mL, the ROC analysis (AUC 0.871, 95% CI 0.787–0.954, p < 0.001) showed a sensitivity of 85.7% and specificity of 78.8% in predicting severe MBrixa scores. Compared to ACE I/I polymorphism, D/D polymorphism significantly increased the risk of severe CXR infiltrates, OR 7.7 (95% CI: 1.9–30.1), and p = 0.002. Significant independent predictors of severe CXR infiltrates include hypertension (OR 7.71), PTX3 (OR 1.20), and ACE D/D polymorphism (OR 18.72). Hypertension (OR 6.91), PTX3 (OR 1.47), and ACE I/I polymorphism (OR 0.09) are significant predictors of poor outcomes. Conclusion: PTX3 and ACE D/D polymorphism are significant predictors of the severity of COVID-19 pneumonia. PTX3 is a significant predictor of death.
This is the first report on a case of perindopril/amlodipine-induced thrombotic microangiopathy (TMA) syndrome. A 48-year-old female was admitted complaining of nettle rash all over the body, bloody ...urine, and weakness shortly after starting antihypertensive therapy with perindopril/amlodipine. Shortly thereafter, she developed pronounced hemiparesis, somnolence, and sensorimotor aphasia. Laboratory findings were compatible with microangiopathic hemolytic anemia and thrombocytopenia. She was diagnosed with TMA. Cessation of perindopril/amlodipine therapy and treatment with plasma exchange and systemic corticosteroids resulted in full recovery. Very seldom perindopril/amlodipine may cause hematologic abnormalities, probably through an immunological mechanism, but there were no reports of causing TMA so far. In our case, the symptoms began shortly after the start of perindopril/amlodipine use. The clinical course of TMA in the case was compatible with TMA related to an acute, immune-mediated drug reaction. The most important thing is to promptly recognize TMA and its induction by a drug because distinctive treatment and cessation of the suspected drug can prevent severe outcome, as it was avoided in our patient.
Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate ...humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin’s lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.
Aim: Multiple myeloma (MM) patients might require haemodialysis (HD) and/or plasma exchange (PE) in cases of acute kidney injury (AKI) and/or chronic kidney disease (CKD) and/or other indications. ...The study analysed the survival of MM patients who required HD and/or PE.
Subjects and methods: All 144 patients treated for MM at the University Hospital Centre Osijek between 1994 and 2018 (of whom 47.9 % were men) were included in the study. Data were collected from medical records. MedCalc Statistical Software version 17.8.2 was used for the statistical analysis, with significance set at α = 0.05.
Results: Forty-three of 144 MM patients (29.9 %) were treated with HD and/or PE. Male patients required HD or PE more often than female patients (62.8 % vs 37.2 %, P = 0.02). Patients who did not require HD or PE were significantly older at the time of their death than the patients treated with HD or PE 75 (interquartile range, IQR, 72 – 77) vs 72 (IQR 66 – 75) years; P = 0.009, Mann-Whitney test. Among all patients who required acute or chronic HD, PE or a combination of the treatments, the longest life span was found in 17 patients who were treated with chronic HD (median 12 months, IQR 8 – 58).
Conclusion: Kidney failure requiring HD or PE in MM was associated with a significantly shorter life span in comparison with other MM patients. Chronic HD patients had the longest survival among patients who required acute or chronic HD, PE or a combination of the treatments. In general, MM patients in need for HD and/or PE had poor survival.
(Smajić* P, Schönberger E, Periša V, Sinčić Petričević J, Zibar L, Kralik K. Survival of Multiple Myeloma Patients Undergoing Dialysis or Plasma Exchange - A Single Centre’s 25-Year Experience. SEEMEDJ 2020; 4(1); 25-31)
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