Effective treatment of Clostridioides difficile infection improves survival and affects graft-versus-host disease: a multicenter study by the Polish Adult Leukemia Group.

Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea after allogeneic hematopoietic cell transplantation (allo-HCT). The impact of CDI and its treatment on allo-HCT outcomes and graft-versus-host disease (GVHD), including gastrointestinal GVHD (GI-GVHD) is not well established. This multicenter study assessed real-life data on the first-line treatment of CDI and its impact on allo-HCT outcomes. Retrospective and prospective data of patients with CDI after allo-HCT were assessed. We noted statistically significant increase in the incidence of acute GVHD and acute GI-GVHD after CDI (P = 0.005 and P = 0.016, respectively). The first-line treatment for CDI included metronidazole in 34 patients, vancomycin in 64, and combination therapy in 10. Treatment failure was more common with metronidazole than vancomycin (38.2% vs. 6.2%; P < 0.001). The need to administer second-line treatment was associated with the occurrence or exacerbation of GVHD (P < 0.05) and GI-GVHD (P < 0.001) and reduced overall survival (P < 0.05). In the multivariate analysis, the risk of death was associated with acute GVHD presence before CDI (hazard ratio [HR], 3.19; P = 0.009) and the need to switch to second-line treatment (HR, 4.83; P < 0.001). The efficacy of the initial CDI treatment affects survival and occurrence of immune-mediated GI-GVHD after allo-HCT. Therefore, agents with higher efficacy than metronidazole (vancomycin or fidaxomicin) should be administered as the first-line treatment.

Case report: VEXAS as an example of autoinflammatory syndrome in pulmonology clinical practice.

Lung involvement is not widely recognized as a complication of auto-inflammatory diseases. We present a broad approach to diagnose a severe form of autoinflammatory syndrome in an adult male patient. A 63-year-old Caucasian male presented with recurrent episodes of high fever, interstitial lung infiltration, and pleural effusion. Laboratory tests performed during the flares revealed lymphopenia and increased levels of C-reactive protein and ferritin. Broad diagnostic research on infections, connective tissue diseases, and malignancies yielded negative results. The patient's symptoms promptly resolved upon the administration of glucocorticoids; however, they reappeared when the prednisone dose was reduced. All attempts to administer immunomodulatory and immunosuppressive medications were ineffective. During follow-up, autoinflammatory syndrome was suspected; however, no pathological variants of monogenic autoinflammatory diseases were identified by genome-exome sequencing. The patient did not respond to interleukin 1 blockade with anakinra. He died due to multi-organ failure, and his condition remained unresolved until the first reported description of vacuole, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome (VEXAS). We describe the diagnostic traps and reasoning process involved in establishing that the patient's symptoms were autoinflammatory in nature based on clinical symptoms, in addition to the proof of concept gained from genetic reevaluation and identification of pathogenic variants in the UBA1 gene. The aim of this review is to increase the awareness of VEXAS among pulmonologists. Genetic screening for UBA1 should be considered in patients with recurrent pneumonitis of unknown origin with elevated inflammatory markers and signs of cytopenia, especially if they require chronic steroids to control the disease. Respiratory manifestations are part of VEXAS; these may be dominant in the course of the disease and severe at presentation.

Altered lipid metabolism in patients with acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for many hematological malignancies and other diseases. Nevertheless, its application is limited due to the risk of life-threatening complications, mainly graft-versus-host disease (GVHD). Currently, in clinical practice, the risk of developing GVHD is estimated for every patient based on factors related to the donor and the host. In our prospective, observational study, we analyzed serum from 38 patients undergoing allo-HCT at our institution. We compared the metabolic profiles of patients who developed acute GVHD (aGVHD) with those without such complication by identification and comparison of metabolites masses on the XCMS platform. We observed that patients diagnosed with aGVHD had different metabolic profiles compared to the remaining patients and this alteration was noticeable already 7 days before the procedure. We identified dysregulated metabolites involved in bile acid transformation and cholesterol synthesis. Our study of the untargeted metabolome in allo-HCT recipients has revealed a potential link between lipid metabolism, specifically involving bile acid transformation and cholesterol synthesis, and the development of aGVHD. This finding might be an important indication for future research focused on understanding GVHD development, discovering prediction models, and investigating possible prophylactic interventions.

Prognostic Impact of Copy Number Alterations' Profile and AID/RAG Signatures in Acute Lymphoblastic Leukemia (ALL) with BCR::ABL and without Recurrent Genetic Aberrations (NEG ALL) Treated with Intensive Chemotherapy.

Adult acute lymphoblastic leukemia (ALL) is associated with poor outcomes. ALL is initiated by primary aberrations, but secondary genetic lesions are necessary for overt ALL. In this study, we reassessed the value of primary and secondary aberrations in intensively treated ALL patients in relation to mutator enzyme expression. RT-PCR, genomic PCR, and sequencing were applied to evaluate primary aberrations, while qPCR was used to measure the expression of RAG and AID mutator enzymes in 166 adult ALL patients. Secondary copy number alterations (CNA) were studied in 94 cases by MLPA assay. Primary aberrations alone stratified 30% of the patients (27% high-risk, 3% low-risk cases). The remaining 70% intermediate-risk patients included BCR::ABL1pos subgroup and ALL lacking identified genetic markers (NEG ALL). We identified three CNA profiles: high-risk bad-CNA (CNAhigh/IKZF1pos), low-risk good-CNA (all other CNAs), and intermediate-risk CNAneg. Furthermore, based on RAG/AID expression, we report possible mechanisms underlying the CNA profiles associated with poor outcome: AID stratified outcome in CNAneg, which accompanied most likely a particular profile of single nucleotide variations, while RAG in CNApos increased the odds for CNAhigh/IKZF1pos development. Finally, we integrated primary genetic aberrations with CNA to propose a revised risk stratification code, which allowed us to stratify 75% of BCR::ABL1pos and NEG patients.

Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells.

Transplantation of hematopoietic stem cells (HSCT) is a procedure commonly used in treatment of various haematological disorders which is associated with significantly improved survival rates. However, one of its drawbacks is the possibility of development of post-transplant complications, including acute and chronic graft-versus-host disease (GvHD) or CMV infection. Various studies suggested that NK cells and their receptors may affect the transplant outcome. In the present study, patients and donors were found to significantly differ in the distribution of the NKG2A rs7301582 genetic variants - recipients carried the C allele more often than their donors (0.975 vs 0.865, p<0.0001). Increased soluble HLA-E (sHLA-E) levels detected in recipients' serum 30 days after transplantation seemed to play a prognostic and protective role. It was observed that recipients with higher sHLA-E levels were less prone to chronic GvHD (11.65 vs 6.33 pg/mL, p=0.033) or more severe acute GvHD grades II-IV (11.07 vs 8.04 pg/mL, p=0.081). Our results also showed an unfavourable role of HLA-E donor-recipient genetic incompatibility in CMV infection development after transplantation (OR=5.92, p=0.014). Frequencies of NK cells (both CD56dim and CD56bright) expressing NKG2C were elevated in recipients who developed CMV, especially 30 and 90 days post-transplantation (p<0.03). Percentages of NKG2C+ NK cells lacking NKG2A expression were also increased in these patients. Moreover, recipients carrying a NKG2C deletion characterized with decreased frequency of NKG2C+ NK cells (p<0.05). Our study confirms the importance of NK cells in the development of post-transplant complications and highlights the effect of HLA-E and NKG2C genetic variants, sHLA-E serum concentration, as well as NKG2C surface expression on transplant outcome.

Biomechanical causes for failure of the Physiomesh/Securestrap system.

This study investigates the mechanical behavior of the Physiomesh/Securestrap system, a hernia repair system used for IPOM procedures associated with high failure rates. The study involved conducting mechanical experiments and numerical simulations to investigate the mechanical behavior of the Physiomesh/Securestrap system under pressure load. Uniaxial tension tests were conducted to determine the elasticity modulus of the Physiomesh in various directions and the strength of the mesh-tissue-staple junction. Ex-vivo experiments on porcine abdominal wall models were performed to observe the system's behavior under simulated intra-abdominal pressure load. Numerical simulations using finite element analysis were employed to support the experimental findings. The results reveal nonlinearity, anisotropy, and non-homogeneity in the mechanical properties of the Physiomesh, with stress concentration observed in the polydioxanone (PDO) stripe. The mesh-tissue junction exhibited inadequate fixation strength, leading to staple pull-out or breakage. The ex-vivo models demonstrated failure under higher pressure loads. Numerical simulations supported these findings, revealing the reaction forces exceeding the experimentally determined strength of the mesh-tissue-staple junction. The implications of this study extend beyond the specific case of the Physiomesh/Securestrap system, providing insights into the mechanics of implant-tissue systems. By considering biomechanical factors, researchers and clinicians can make informed decisions to develop improved implants that mimic the mechanics of a healthy abdominal wall. This knowledge can contribute to better surgical outcomes and reduce complications in abdominal hernia repair and to avoid similar failures in future.

Melatonin increases collagen content accumulation and Fibroblast Growth Factor-2 secretion in cultured human cardiac fibroblasts.

BACKGROUND: The extracellular matrix serves as a scaffold for cardiomyocytes, allowing them to work in accord. In rats, collagen metabolism within a myocardial infarction scar is regulated by melatonin. The present study determines whether melatonin influences matrix metabolism within human cardiac fibroblast cultures and examines the underlying mechanism. METHODS: The experiments were performed on cultures of cardiac fibroblasts. The Woessner method, 1,9-dimethylmethylene blue assay, enzyme-linked immunosorbent assay and quantitative PCR were used in the study. RESULTS: Melatonin treatment lowered the total cell count within the culture, elevated necrotic and apoptotic cell count as well as augmented cardiac fibroblast proliferation, and increased total, intracellular, and extracellular collagen within the fibroblast culture; it also elevated type III procollagen α1 chain expression, without increasing procollagen type I mRNA production. The pineal hormone did not influence matrix metalloproteinase-2 (MMP-2) release or glycosaminoglycan accumulation by cardiac fibroblasts. Melatonin increased the release of Fibroblast Growth Factor-2 (FGF-2) by human cardiac fibroblasts, but cardiotrophin release was not influenced. CONCLUSION: Within human cardiac fibroblast culture, collagen metabolism is regulated by melatonin. The profibrotic effect of melatonin depends on the elevation of procollagen type III gene expression, and this could be modified by FGF-2. Two parallel processes, viz., cell elimination and proliferation, induced by melatonin, lead to excessive replacement of cardiac fibroblasts.

Is mesh fixation necessary in laparoendoscopic techniques for M3 inguinal defects? An experimental study.

BACKGROUND: Although international guidelines recommend not fixing the mesh in almost all cases of laparoendoscopic repairs, in case of large direct hernias (M3) mesh fixation is recommended to reduce recurrence risk. Despite lack of high-quality evidence, the recommendation was upgraded to strong by expert panel. The authors conducted a research experiment to verify the hypothesis that it is possible to preserve the mesh in the operating field in large direct hernias (M3) without the need to use fixing materials. METHOD: The authors conducted an experiment with scientists from Universities of Technology in a model that reflects the conditions in the groin area. By simulating conditions of the highest possible intra-abdominal pressure, they examined the mesh behavior within the groin and its ability to dislocate under the forces generated by this pressure. The experiment involved six spatial implants and one flat macroporous mesh. RESULTS: Heavyweight spatial meshes and lightweight spatial-individualized meshes showed no tendency to dislocate or move directly to the orifice, which was considered a rapid hernia recurrence. Lightweight meshes, both spatial and flat, underwent significant migration and shifting toward the hernial orifices. CONCLUSION: Based on the results, we believe that mesh fixation is not the only alternative to preventing recurrence in complex defects. Similar effects can be achieved using a larger, more rigid, and anatomically fitted implant. The type of implant (rather than its fixation) seems to be a key factor from the point of view of mechanics and biophysics. Clinical trials confirming the results in vivo will allow to supplement or amend the guidelines for the treatment of large inguinal hernias.

Speciation Analysis Highlights the Interactions of Auranofin with the Cytoskeleton Proteins of Lung Cancer Cells.

Two types of lung cells (epithelial cancer lung cells, A-549 and lung fibroblasts MRC-5) were exposed to the clinically established gold drug auranofin at concentrations close to the half-maximal inhibitory drug concentrations (IC50). Collected cells were subjected to speciation analysis using inductively coupled plasma mass spectrometry (ICP-MS). Auranofin showed better affinity toward proteins than DNA, RNA, and hydrophilic small molecular weight compounds. It can bind to proteins that vary in size (~20 kDa, ~75 kDa, and ≥200 kDa) and pI. However, the possibility of dimerization and protein-protein complex formation should also be taken into account. µRPLC/CZE-ESI-MS/MS studies on trypsinized proteins allowed the indication of 76 peptides for which signal intensity was influenced by auranofin presence in cells. Based on it, identity was proposed for 20 proteins. Except for thioredoxin reductase (TrxR), which is directly targeted by gold complex, the proteins were found to be transformed. Five indicated proteins: myosin, plectin, talin, two annexins, and kinase M3K5, are responsible for cell-cell, cell-protein interactions, and cell motility. A wound healing test confirmed their regulation by auranofin as cell migration decreased by 40% while the cell cycle was not interrupted.

Gitelman syndrome with normocalciuria - a case report.

BACKGROUND: Gitelman Syndrome (GS) is a hereditary tubulopathy associated with a biallelic inactivating mutations of the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT). The typical clinical manifestation is a hypokalemic metabolic alkalosis with significant hypomagnesemia, and low urinary calcium excretion. Hypocalciuria is widely believed to be a hallmark of GS that distinguishes it from Barter's syndrome, presenting as hypercalciuria. The pathomechanism of hypocalciuria in GS is not fully elucidated. Up to date, a clinical course of GS with normocalciuria has been reported only in men, while women have a milder course of the disease with typical hypocalciuria, which is believed as the result of sex hormone. Additionally, there is a growing evidence that calcium channels of the distal nephron could be regulated by a variety of hormones, including aldosterone (Aldo). CASE PRESENTATION: We present the case of a 28-year-old Caucasian woman with asymptomatic, chronic hypokalemia, hypomagnesemia, hypochloremic alkalosis and normal urinary calcium excretion. A high renin levels with normal concentration of Aldo in serum have also been found. The values of blood pressure were low. Based on genetic studies, two heterozygous mutations in the trans position were confirmed: c.2186G>T (p.Gly729Val) and c.1247G>C (p.Cys416Ser) in the SLC12A3 gene, which ultimately confirmed the diagnosis of GS. CONCLUSIONS: We report here the first case of genetically confirmed GS manifested as normocalciuria in a Caucasian woman. Thus, our result does not confirm a role of sex hormones on the level of calciuria. Based on the results of normal Aldo concentration despite high renin level in our patient, we hypothesized that Aldo may be connecting with the level of urinary calcium excretion in patients with the GS.

Increase Urinary Biomarkers of Kidney Injury in Patients After Allogenic Hematopoietic Stem Cell Transplant Reflect Kidney Damage Even in Normal Kidney Function.

Kidney function in patients undergoing hematopoietic stem cell transplant (HSCT) is frequently worsened by previous chemotherapy and exposure to a variety of nephrotoxic drugs. The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after HSCT under ambulatory care of the Hematology, Oncology and Internal Medicine Department. We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtain normal ranges for biomarkers. In this cross-sectional study, the following biomarkers of kidney injury in urine were evaluated using commercially available assays: IGFBP7 and TIMP2, netrin-1, and semaphorin A2. All of the biomarkers studied were significantly higher in patients after HSCT compared with the healthy volunteers. When we divided patients according to kidney function (below and over 60 mL/min/1.73m2), we found that only concentration of IGFBP7 was significantly higher in 23 patients with chronic kidney disease (CKD) stage 3 relative to patients with an estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73m2. All biomarkers in both subgroups of patients with eGFRs below and over 60 mL/min/1.73m2 were significantly higher relative to healthy volunteers. In univariate correlations, semaphorin A2 was related to netrin-1 (r = 0.47, P < .001), IGFBP7 (r = 0.35, P < .01), and TIMP2 (r = 0.32, P < .01), whereas IGFBP7 was positively related to serum creatinine (r = 0.38, P < .001) and inversely to eGFR (r = -0.36, P < .001). Patients after allogeneic HSCT, despite normal or near normal kidney function, show evidence of kidney injury.

Molecular Background and Disease Prevalence of Biotinidase Deficiency in a Polish Population-Data Based on the National Newborn Screening Programme.

Biotinidase deficiency (BD) is a rare autosomal recessive metabolic disease. Previously the disease was identified only by clinical signs and symptoms, and since recently, it has been included in newborn screening programs (NBS) worldwide, though not commonly. In Europe, BD prevalence varies highly among different countries, e.g., from 1:7 116 in Turkey to 1:75 842 in Switzerland. This paper aimed to present the molecular spectrum of BD (profound and partial forms) in Polish patients diagnosed within the national NBS of 1,071,463 newborns. The initial suspicion of BD was based on an abnormal biotinidase activity result determined in a dry blood spot (DBS) by colorimetric and by fluorimetric methods while biochemical verification was determined by serum biotinidase activity (as quantitative analysis). The final diagnosis of BD was established by serum enzyme activity and the BTD gene direct sequencing. The obtained results allowed for the estimation of disease prevalence (1:66,966 births, while 1:178,577 for profound and 1:107,146 for partial forms), and gave novel data on the molecular etiology of BD.

Clinical Importance of aCGH in Genetic Counselling of Children with Psychomotor Retardation.

Introduction: The X and Y chromosomes are responsible for the determination and differentiation of the gonads, and their numerical and structural abnormalities may cause the abnormal development of secondary sex characteristics. The presence of abnormalities concerning X chromosome can also contribute to many genetically heterogeneous diseases associated with cognitive impairment and intellectual disability. Purpose: This study shows the effect of aberrations of the maternal X chromosome on the abnormal development of the child. Patients and Methods: Ten women aged 26 to 40 years were consulted in genetic counselling clinic and subsequently subjected to cytogenetic and molecular tests due to abnormal psychomotor development of their children, in whom structural aberrations of the X chromosome had been detected. Results: Two women were diagnosed with changes in karyotype: 46,X,der(X)t(X;Y)(p22.3;q11.2) in one and 46,X,inv(X)(p21.2q13). Five women were diagnosed with microduplications in the short arm of the X chromosome; dupXp22.31 in one, and in four women dupXp22.33. The remaining three women were diagnosed with duplication in the long arm of the X chromosome; dupXq25 in one and dupXq26.3 in two women. Conclusion: Genetic analysis of the X chromosome, based on cytogenetic and molecular methods of the highest available resolution, is extremely important in women with reproductive failure. These methods allow establishing accurately the breakpoints and rearrangements in chromosomes, and assessment of the copy number variation (CNV) can explain phenotypic variability with apparently similar aberrations. A more precise characterization of the alterations is necessary for the correct genetic diagnosis, as well as determination of the carrier status and genetic risk in family members.

Sex determination from human patella in a Polish medieval sample.

This study aimed to address whether the anthropometric features of the patella can be used to determine the sex of the individuals on the basis of the skeletal remains and to set limit values for anthropometric measurements and indicators of the patella in relation to each sex. 71 patellas (32 female and 39 male) from the Middle Ages from Wroclaw, Poland, were analyzed. The measurements (the greatest height, width, thickness, width of the lateral and medial joint surface and the height of these joint surfaces) and ratios were calculated (height to width, height to thickness as well as width to height of lateral and medial joint surfaces) and tested according to sexual dimorphism. The best parameter in terms of discriminatory assessment was the patella's highest height, which made it possible to classify the sex in 46.5% of cases. However, an index of the sum of the height, width and thickness measurements seems to be even better for differentiating between the sexes, making it possible to correctly classify the sex in 49.3% of cases. Due to some limitations of this study and the need of population-specific standard, it is recommend to employ the patella in sex determination only in cases of fragmented human remains and when no other method can be applied. Further investigation of possible factors influencing the variability of its size and shape should be explored in larger and geographically more diverse samples, and this could contribute to forensic, clinical, anatomical, and anthropological studies in this body part.

Chronic Kidney Disease in Patients After Allogeneic Hematopoietic Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is used in advanced hematologic diseases to restart the immune system. Kidney damage remains significant complication of hematopoietic cell transplant (HCT) affecting the mortality of transplant recipients. The aim of the study was to assess the advancement of chronic kidney disease (CKD) in patients after HSCT. We studied 150 patients who underwent allo-HSCT treatment in our center in years 1995 to 2020 because of acute myeloid leukemia in 47% of patients, acute lymphoblastic leukemia in 19%, and lymphoma in 32%. The mean age of patients with acute leukemia is 48 years (including acute myeloid leukemia it is 47 years, and including acute lymphoblastic leukemia it is 32 years). The mean age of lymphoma patients is 34 years. We studied the prevalence and stages of CKD. CKD stage 3a and 3b was found in 24.6%. None of the patients studied had CKD stage 4 or 5. In patients after HSCT because of both acute myeloid leukemia and acute lymphoblastic leukemia, CKD stage 3a was found in 19% and stage 3b in 7.3%. Estimated glomerular filtration rate (eGFR) >90 mL/min/1.73 m2, was found in 36.8% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m2 was observed in 36.8%. In patients with lymphoma who underwent HSCT, CKD stage 3a was found in 18%, while CKD stage 3b was diagnosed in 27% of the patients. An eGFR >90 mL/min/1.73 m2, was found in 27% of this population, whereas eGFR between 90 and 60 mL/min/1.73 m2 was observed in 27% of patients. The categorization of patients according to the underlying disease is important because other drugs are used in therapy of conditioning before HCT. CKD in patients after allogeneic HSCT is common, although advanced stages were not observed, probably because the age of the population studied was not advanced. CKD in these vulnerable patients may be because of prior chemotherapy, conditioning regimen, post-HSCT calcineurin therapy, and other possible nephrotoxic drugs.

Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT.

While in vivo T-cell depletion (TCD) is widely used, its benefit in patients with MDS still remains a matter of debate. This study evaluates the impact of TCD on outcomes, and compares ATG and alemtuzumab, in patients with MDS. 1284 patients from the EBMT registry were included in this study with 470 patients in the no-TCD group and 814 in the TCD group (alemtuzumab N = 168; ATG N = 646). At 6 months, aGVHD III-IV cumulative incidences (CI) for no-TCD, ATG or alemtuzumab groups were 13% vs 14% vs 11% (ns), respectively. At 5 years, CI of chronic GVHD were 64% vs 52% vs 51% (p < 0.00017); and CI of relapse was 23% vs 25% vs 39% (p < 0.0001) for no TCD, ATG and alemtuzumab respectively; OS was 47% vs 46% vs 34% (p = 0.009) respectively; and GRFS was 21% vs 28% and 20% (p = 0.045) respectively. In multivariable analysis, ATG improved GRFS, and alemtuzumab decreased OS. Both ATG and alemtuzumab decreased risk of chronic GVHD, but the increased risk of relapse with alemtuzumab is associated with a poor GRFS and suggest to not use alemtuzumab in the setting of allo-SCT for high risk disease.

A novel in vivo approach to assess strains of the human abdominal wall under known intraabdominal pressure.

The study concerns mechanical behaviour of a living human abdominal wall. A better mechanical understanding of a human abdominal wall and recognition of its material properties is required to find mechanically compatible surgical meshes to significantly improve the treatment of ventral hernias. A non-invasive methodology, based on in vivo optical measurements is proposed to determine strains of abdominal wall corresponding to a known intraabdominal pressure. The measurement is performed in the course of a standard procedure of peritoneal dialysis. A dedicated experimental stand is designed for the experiment. The photogrammetric technique is employed to recover the three-dimensional surface geometry of the anterior abdominal wall at the initial and terminal instants of the dialysis. This corresponds to two deformation states, before and after filling the abdominal cavity with dialysis fluid. The study provides information on strain fields of living human abdominal wall. The inquiry is aimed at principal strains and their directions, observed at the level from -10% to 17%. The intraabdominal pressure related to the amount of introduced dialysis fluid measured within the medical procedure covers the range 11-18.5 cmH2O. The methodology leads to the deformation state of the abdominal wall according to the corresponding loading conditions. Therefore, the study is a step towards an identification of mechanical properties of living human abdominal wall.

Combined numerical and experimental approach to determine numerical model of abdominal scaffold.

A proper junction of the prosthesis and the abdominal wall is important in successful hernia repair. The number of tacks should be balanced to assure appropriate mesh fixation and not to induce post-operative pain. Numerical simulations help to find this balance. The study is aimed at creating a proper numerical model of a knitted surgical mesh subjected to boundary conditions and load occurring in the abdominal cavity. Continuous, anisotropic constitutive relation is considered to reflect the mesh behaviour. Different sets of material law parameters are determined on the basis of different bi-axial tests setups. Force- and displacement-controlled tests with different ratios are considered. Consequently, some numerical model variants are obtained featuring various reaction distributions in the scaffold fixation points. The proper variant is selected based on comparison of the position of maximal reaction force in the numerical model and in the reference physical model of operated hernia. Force-driven tests have shown anisotropic mesh behaviour, while equibiaxial displacement-driven test has demonstrated reduced anisotropic response. Within seven scenarios of constitutive parameters identification (based on single or combined experimental data), the equibiaxial force-controlled test appeared to produce the most relevant model to follow the prosthesis behaviour under pressure. The position of maximal reaction force in such model is similar to obtained in the physical hernia model. The equibiaxial force-driven test provides most suitable data for Gasser-Ogden-Holzapfel constitutive model identification of a considered surgical mesh to be used to model the mesh under pressure.

Potent but transient immunosuppression of T-cells is a general feature of CD71+ erythroid cells.

CD71+ erythroid cells (CECs) have been recently recognized in both neonates and cancer patients as potent immunoregulatory cells. Here, we show that in mice early-stage CECs expand in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). In the spleens of anemic mice, CECs expansion-induced L-arginine depletion suppresses T-cell responses. In humans with anemia, CECs expand and express ARG1 and ARG2 that suppress T-cells IFN-γ production. Moreover, bone marrow CECs from healthy human donors suppress T-cells proliferation. CECs differentiated from peripheral blood mononuclear cells potently suppress T-cell activation, proliferation, and IFN-γ production in an ARG- and ROS-dependent manner. These effects are the most prominent for early-stage CECs (CD71highCD235adim cells). The suppressive properties disappear during erythroid differentiation as more differentiated CECs and mature erythrocytes lack significant immunoregulatory properties. Our studies provide a novel insight into the role of CECs in the immune response regulation.

Ice-cream used as cryotherapy during high-dose melphalan conditioning reduces oral mucositis after autologous hematopoietic stem cell transplantation.

Oral mucositis (OM) is one of the most frequent adverse events of high-dose conditioning chemotherapy with melphalan prior to autologous hematopoietic stem cell transplantation (AHSCT). It significantly reduces the patients' quality of life. One of the preventive strategies for OM is cryotherapy. We retrospectively analyzed whether commercially available ice-cream could prevent OM during the melphalan infusion. We retrospectively analyzed 74 patients after AHSCT to see whether there is any correlation between OM and cryotherapy (ice-cream), melphalan dose (140 mg/m2 or 200 mg/m2). The incidence of OM in our study inversely correlated with cryotherapy in the form of ice-cream. Out of 74 patients receiving conditioning chemotherapy with high-dose melphalan, 52 received cryotherapy. Fifteen patients in the cryotherapy group (28.84%) developed OM, whereas 13 patients (59.09%) developed it in the group without cryotherapy. In a multiple linear regression test cryotherapy remained a significant protective factor against OM (p = 0.02) We have also seen the relationship between melphalan dose with OM (p < 0.005). Cryotherapy in the form of ice-cream is associated with a lower rate of OM and, therefore, could potentially be used as a cost-effective, less burdensome, and easy to implement method in prevention of oral mucositis.