Daily serum phosphate increase as early and reliable indicator of kidney injury in children with leukemia and lymphoma developing tumor lysis syndrome.

BACKGROUND: Tumor lysis syndrome (TLS) and its most serious complication, acute kidney injury (AKI) are one of the emergency conditions in onco-hematology. It is difficult to predict the degree of kidney involvement. Therefore, we studied children with leukemia and lymphoma treated in four Hungarian tertiary centers (inpatient university clinics) retrospectively (2006-2016) from a nephrological aspect. METHOD: Data of 31 pediatric patients were obtained from electronic- and paper-based medical records. Physical status, laboratory test results, treatments, and outcomes were assessed. Patients were analyzed according to both "traditional" TLS groupings, as laboratory TLS or clinical TLS, and nephrological aspect based on pRIFLE classification, as mild or severe AKI. RESULTS: Significant differences were found between the changes in parameters of phosphate homeostasis and urea levels in both classifications. Compared to age-specific normal phosphate ranges, before the development of TLS, hypophosphatemia was common (19/31 cases), while in the post-TLS period, hyperphosphatemia was observed (26/31 cases) most frequently. The rate of daily change in serum phosphate level was significant in the nephrological subgroups, but peaks of serum phosphate level show only a moderate increase. The calculated cut-off value of daily serum phosphate level increased before AKI was 0.32 mmol/L per ROC analysis for severe TLS-AKI. The 24-h urinalysis data of eight patients revealed transiently increased phosphate excretion only in those patients with TLS in whom serum phosphate was elevated in parallel. CONCLUSION: Daily serum phosphate level increase can serve as a prognostic factor for the severity of pediatric TLS, as well as predict the severity of kidney involvement. A higher resolution version of the Graphical abstract is available as Supplementary information.

Epidemiology and clinical features of SARS-CoV-2 infection in hospitalized children across four waves in Hungary: A retrospective, comparative study from March 2020 to December 2021.

Background and Aims: From 2019 till the present, infections induced by the novel coronavirus and its mutations have posed a new challenge for healthcare. However, comparative studies on pediatric infections throughout waves are few. During four different pandemic waves, we intended to investigate the clinical and epidemiological characteristic of the pediatric population hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection. Methods: Between March 2020 and December 2021, we performed our retrospective research on children infected with the SARS-CoV-2 virus at the University of Szeged. We analyzed the data of all patients who required hospitalization due to positive results of SARS-CoV-2 tests (Nucleic Acid Amplification Test or rapid antigen test). Data analysis included demographic data, medical history, clinical findings, length of hospitalization, and complications, using medical records. Results: In this study, data from 358 coronavirus-infected children were analyzed. The most affected age group was children over 1 month and under 1 year (30.2%). The highest number of cases was recorded in the fourth wave (53.6%). Fever (65.6%), cough (51.4%), nasal discharge (35.3%), nausea and vomiting (31.3%), and decreased oral intake (28.9%) were the most common symptoms. The most common complications were dehydration (50.5%), pneumonia (14.9%), and bronchitis/bronchiolitis (14.5%). Based on RR values, there are considerable differences in the prevalence of the symptoms and complications between the different age groups and waves. Cox proportional hazard model analyzes showed that fever and tachypnoea had a relevant effect on days to recovery. Conclusions: We found trends similar to those previously published, overall statistics. The proportion of children requiring hospitalization varied from wave to wave, with the fourth wave affecting the Hungarian child population the most. Our findings suggest that hospitalization time is unrelated to age, but that certain symptoms (fever and tachypnoea) are associated with longer hospitalization. The onset of certain symptoms may differ by age group.

FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy.

Background: Factor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data. Methods: A total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR). Results: Eight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters. Conclusions: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

BACKGROUND: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. METHODS: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. RESULTS: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2. CONCLUSIONS: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups.

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy.

BACKGROUND: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. RESULTS: One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. CONCLUSIONS: In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients.

Left ventricular rigid body rotation in a diffuse large B-cell lymphoma patient with cardiac involvement: A case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

Secondary myocardial involvement by diffuse large B-cell lymphoma is a rare occurrence. Left ventricular (LV) twist is considered an essential part of LV function. In normal circumstances LV twist results from the movement of two orthogonally oriented muscular bands of a helical myocardial structure with consequent clockwise rotation of the base and counterclockwise rotation of the apex. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) has been found to be feasible for non-invasive 3D quantification of LV wall motion and rotational mechanics. The present report aimed to assess LV twisting motion in a patient with diffuse large B-cell lymphoma with positron emission tomography/computer tomography-proven cardiac involvement by 3DSTE. During 3DSTE, reduction in some segmental radial, longitudinal, circumferential, area and 3D LV strains were found. Apical and basal LV rotations were found to be in the same counterclockwise direction, confirming near absence of LV twist - so-called rigid body rotation.

Efficient Targeted Next Generation Sequencing-Based Workflow for Differential Diagnosis of Alport-Related Disorders.

Alport syndrome (AS) is an inherited type IV collagen nephropathies characterized by microscopic hematuria during early childhood, the development of proteinuria and progression to end-stage renal disease. Since choosing the right therapy, even before the onset of proteinuria, can delay the onset of end-stage renal failure and improve life expectancy, the earliest possible differential diagnosis is desired. Practically, this means the identification of mutation(s) in COL4A3-A4-A5 genes. We used an efficient, next generation sequencing based workflow for simultaneous analysis of all three COL4A genes in three individuals and fourteen families involved by AS or showing different level of Alport-related symptoms. We successfully identified mutations in all investigated cases, including 14 unpublished mutations in our Hungarian cohort. We present an easy to use unified clinical/diagnostic terminology and workflow not only for X-linked but for autosomal AS, but also for Alport-related diseases. In families where a diagnosis has been established by molecular genetic analysis, the renal biopsy may be rendered unnecessary.

[Sentinel lymph node biopsy for in situ carcinoma of the breast. Experience at the Bács-Kiskun County Hospital and review of the literature]. / Orszemnyirokcsomó-biopszia in situ emlorákban. A Bács-Kiskun Megyei Onkormányzat Kórházának tapasztalatai és irodalmi összefoglalás.

UNLABELLED: Sentinel node biopsy (SNB) is controversial for in situ breast cancers. We reviewed our experience with in situ and microinvasive carcinomas and surveyed the literature. METHODS: SNB was performed with intraparenchymal administration of vital dye alone or combined with radiocolloid. The SNs were assessed histologically with haematoxylin eosin staining and cytokeratin immunohistochemistry. RESULTS: Patients with in situ (36) or microinvasive (20) carcinomas underwent SNB: 59 axillary and 1 parasternal, and 39 axillary and 1 parasternal SNs were recovered, respectively. The SNs were positive in 4 patients and 1 patient, respectively: 1 micrometastasis and 3 isolated tumour cells, and 1 micrometastasis in the respective groups. No further axillary nodes were found positive after dissection. Further 21 invasive carcinomas (often with extensive intraductal component) had an in situ carcinoma diagnosis preoperatively: of 39 axillary and 3 parasternal SNs 10 patients had nodal involvement in 13 axillary SNs; 5 patients also had further lymph nodes involved after dissection. CONCLUSIONS: The definitive diagnosis of in situ carcinoma does not warrant SNB. This procedure should be considered if the tumour is to be removed by mastectomy, or if the diagnosis is preoperative and there are associated high-risk factors for the subsequent diagnosis of invasive cancer.

[Early clinical experience with postoperative monitoring of a patient after laparoscopic splenectomy combined with spleen autotransplantation. A case report]. / Minimálisan invazív módszerrel végzett, lép autotranszplantált beteg posztoperatív követésére alkalmazott képalkotó eljárásokkal nyert kezdeti tapasztalataink. Esetismertetés.

We performed splenectomy combined with spleen autotransplantation after blunt abdominal trauma by minimally invasive technique at the County Teaching Hospital in Kecskemét. In case of advanced post traumatic spleen injury, spleen autotransplantation (Furka's spleen chips) is a well-known method to try to avoid postsplenectomy syndrome. During the operation, when in situ preservation of the spleen is not possible, chips of spleen tissue are transplanted into the omentum. Function of the transplanted spleen tissue was monitored by scintigraphy. We describe two different types of spleen scintigraphy to check the viability of spleen chips.

Use and limitations of a nomogram predicting the likelihood of non-sentinel node involvement after a positive sentinel node biopsy in breast cancer patients.

After a positive sentinel lymph node (SLN) biopsy, some patients may be considered to have a very low risk of non-SLN involvement and could be candidates for axillary sparing. The aim of this study was to validate the nomogram created at the Memorial Sloan-Kettering Cancer Center (MSKCC) for the prediction of non-SLN involvement in an independent set of 140 patients with both positive SLNs and axillary dissection. The predicted proportions of positive non-SLNs were compared with the observed percentages of non-SLN metastasis. Although the SLN metastasis size and tumor size did influence the risk of non-SLN involvement, the correlation between the predicted and observed proportions was weaker for our patients (R: 0.84) than for the patients assessed at the MSKCC (R: 0.97). Differences were noted in the intraoperative assessment and in the final histology of the SLNs (imprints vs frozen sections and more detailed vs less detailed, respectively), and these could partly explain the lower level of the correlation. The nomogram could not be validated and was found to be of only limited use for the prediction of non-SLN involvement in patients operated on under similar, though not fully identical conditions. We therefore warn against the unvalidated use of this prediction tool.

Axillary sentinel node and tumour-related factors associated with non-sentinel node involvement in breast cancer.

BACKGROUND: After completion of axillary dissection, many breast cancer patients with axillary sentinel nodal involvement are found to have regional disease limited to the sentinel nodes. These patients are exposed to the morbidity of axillary clearance without any expected therapeutic benefit. METHODS: Sentinel node biopsy was performed either with Patent blue dye or with a combined dye, radiocolloid and gamma-probe-guided method involving peritumoral tracer administration. For a series of 150 consecutive patients with involved axillary sentinel nodes and axillary dissection, factors associated with non-sentinel nodal involvement were analysed in a multivariate analysis based on logistic regression with the use of fractional polynomials. RESULTS: The following variables were found to be potentially associated with non-sentinel node metastases: tumour size, sentinel node metastasis size, number of examined sentinel nodes, percentage of involved sentinel nodes (the latter two were found to be significant only when in combination), and extracapsular perinodal spread. CONCLUSIONS: Isolated tumour cells and micrometastases in axillary sentinel nodes carry a low risk of non-sentinel node metastasis. The risk of metastasis to further echelon nodes is higher with macrometastases, especially if there is extracapsular growth and the proportion of involved sentinel nodes is high.

Comparison of vital dye-guided lymphatic mapping and dye plus gamma probe-guided sentinel node biopsy in breast cancer.

The optimal technique for sentinel lymph node biopsy (SLNB) is still debated. SLNB with peritumoral injection of Patent blue dye was performed in 129 clinically T1-T2 and N0 breast cancers in 127 patients (group A); it was later replaced by combined dye and radiocolloid-guided SLNB preceded by lymphoscintigraphy in 72 breast cancer patients (group B). This study compares these two methods. All patients underwent completion axillary dissection. Means of 1.4 and 1.3 SLNs were identified in groups A and B, respectively. The mean number of non-SLNs for the whole series was 14.9 (range 5-42). The first 53 cases of lymphatic mapping (dye only) comprised the institutional learning period during which the identification rate of at least 1 SLN in 30 consecutive attempts reached 90%. The identification rate for the subsequent 76 group A patients was 92%. The accuracy rate of SLNBs for overall axillary nodal status prediction and the false-negative rate for group A patients (after excluding the learning-phase cases) were 93% and 10%, respectively. All 72 group B cases had at least one SLN identified, and only one false-negative case occurred in this group (accuracy and false-negative rates of 99% and 3%, respectively). Both the dye-only and the combined SLNB methods are suitable for SLN identification, but the latter works better and results in higher accuracy, a higher negative predictive value, and a lower false-negative rate. It is therefore the method of choice.

[Sentinel node biopsy for breast cancer patients at the Bács-Kiskun County Teaching Hospital]. / Emlórákos betegek axillaris órszem nyirokcsomó biopsiájának gyakorlata a Bács-Kiskun Megyei Onkormányzat Kórházában.

INTRODUCTION: The optimal technique of sentinel node biopsy (SNB) is still debated. AIMS: To compare two methods of SNB, describe the learning phase, the validation of the methods and the first results after implementing SNB as standard of care in selected breast cancer patients. PATIENTS AND METHODS: SNB with peritumoral or intratumoral injection of Patent blue dye only was performed in 129 clinically T1-T2 and N0 breast cancers in 127 patients (Group A); it was later replaced by combined dye and radiocolloid-guided SNB preceded by lymphoscintigraphy in 72 breast cancer patients (Group B). All patients underwent completion axillary dissection. Group C, to date, comprises 50 patients, in whom axillary dissection was performed on the basis of the SNB. Intraoperative imprint cytology was performed, and whenever positive, the axillary dissection was completed in the same step, whereas in cases of negative cytology findings but positive final histology, the dissection was done as a second operation. Histopathological assessment of SNs involved step sectioning and immunohistochemistry. RESULTS: Means of 1.4 and 1.3 SNs were identified in Groups A and B, respectively. The mean number of non-SNs for the whole series was 14.7 (range 5-42). The first 53 cases of lymphatic mapping with patent blue dye comprised the institutional learning period, during which the identification rate of at least 1 SN in 30 consecutive attempts reached 90%. The identification rate for the subsequent 76 Group A patients was 92%. The accuracy of SNB for overall axillary nodal status prediction and the false-negative rate for Group A patients (after exclusion of the learning-phase cases) were 93% and 10%, respectively. All 72 Group B cases had at least 1 SN identified, and only 1 false-negative case occurred in this group, i.e. the accuracy and false-negative rate were 99% and 3%, respectively. The identification rate in Group C was 98%; axillary dissection could be avoided in 25 patients, it was performed at the same time as the SNB in 15 and as a second operation in 10. Till now, no axillary recurrence was detected in Group C patients, although the follow-up period is short for the moment. CONCLUSIONS: The dye only and the radioguided SNB methods are complementary, their combination improves the performance, and can be the basis of performing axillary dissection on the basis of SNB results. After the technique of SNB has been validated in a given institution, it can become standard of care in a well selected group of patients, but requires a close follow up.