Supporting the Diagnosis of Fabry Disease Using a Natural Language Processing-Based Approach.

In clinical practice, the consideration of non-specific symptoms of rare diseases in order to make a correct and timely diagnosis is often challenging. To support physicians, we developed a decision-support scoring system on the basis of retrospective research. Based on the literature and expert knowledge, we identified clinical features typical for Fabry disease (FD). Natural language processing (NLP) was used to evaluate patients' electronic health records (EHRs) to obtain detailed information about FD-specific patient characteristics. The NLP-determined elements, laboratory test results, and ICD-10 codes were transformed and grouped into pre-defined FD-specific clinical features that were scored in the context of their significance in the FD signs. The sum of clinical feature scores constituted the FD risk score. Then, medical records of patients with the highest FD risk score were reviewed by physicians who decided whether to refer a patient for additional tests or not. One patient who obtained a high-FD risk score was referred for DBS assay and confirmed to have FD. The presented NLP-based, decision-support scoring system achieved AUC of 0.998, which demonstrates that the applied approach enables for accurate identification of FD-suspected patients, with a high discrimination power.

Effect of intravenous iron on endogenous erythropoietin and FGF-23 secretion in patients with chronic kidney disease.

INTRODUCTION: It has been observed that intravenous iron administration may suppress endogenous production of erythropoietin (EPO). We postulate that this effect may be mediated by increased FGF-23 secretion. AIM OF THE STUDY: To evaluate the short-term effect of intravenous iron sucrose administration on endogenous EPO secretion in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: The cohort comprised 35 nondialysis patients with CKD stages 3-5. All received 100 mg of intravenous iron (III)-hydroxide sucrose complex daily for five consecutive days. Plasma EPO, iFGF-23, cFGF-23, PTH, bone alkaline phosphatase (BAP), phosphorus (PO4), calcium (Ca), and high-sensitive C-reactive protein (CRP) were measured before, and two hours after, the first and third iron infusions, and after completing iron therapy. RESULTS: EPO concentration at the end of iron treatment was significantly lower than two hours after the first iron infusion (p = 0.0003) and before the third dose (p = 0.0006) (12.6 [10.2, 41.4] mIU/mL. vs. 30.9 [15.9, 54.2] mIU/mL and 33.4 [15.4, 56.7] mIU/mL, respectively). Conversely, plasma iFGF-23 was significantly higher before the third dose (61.1 [18.6, 420.1 4] pg/mL; p = 0.025) and after the course of treatment (92.1 [28.4, 878.1] pg/mL; p = 0.004) compared to pretreatment value (48.4 [16.2, 420] pg/mL). cFGF-23 concentration was significantly lower than baseline after the first iron dose (491.8 [257.7, 1086.3] vs. 339.2 [75.4, 951.2] RU/mL; p = 0.005) and after treatment (398.7 [90.4, 1022.3] RU/mL; p = 0.025). No significant linear correlation was found between changes in plasma EPO and FGF-23. CONCLUSIONS: Although intravenous iron therapy causes parallel increase of FGF-23 and supression of endogenous EPO, these two effects seem to be independent.

[Diagnostic challenges in Kimura's disease]. / Wyzwania w diagnostyce choroby Kimury.

Ultra-rare diseases occur with a frequency of 2 in 100 000 people or less. Kimura's disease (KD) affects less than 1 in 1 000 000 people. It is a benign, chronic inflammatory soft tissue disorder, accompanied by eosinophilia, raised immunoglobulin E (IgE) titer and the presence of painless subcutaneous masses, usually in the head and neck region. The disease was first described in 1948 and occurs at higher rates in Asia than in America or Europe. A CASE REPORT: A 35-year-old man without past medical history presented to his family doctor for bilateral cervical lymphadenopathy accompanied by eosinophilia. Despite subsequent in-depth diagnostics, including fine-needle aspiration biopsy (FNAB) of the lymph nodes, the definitive diagnosis was not initially established. After following 2 months, a selective lymphadenectomy was performed, putting Hodgkin's lymphoma under suspicion. The image of positron emission tomography coupled with computed tomography (PET-CT) corresponded to this diagnosis. Due to the lack of all the criteria necessary to make a diagnosis, another histopathological consultation was done. The image of the lymph nodes suggested reaction-inflammatory changes. Due to the presence of a triad of signs (reactive lymphadenopathy, several eosinophils in the paracortic zone, vascular proliferation), differential diagnosis was recommended, among others towards the Kimura's disease. A series of examinations allowed to exclude lymphadenopathy of parasitic, allergic and hyperplastic hematopoietic system aetiology. The patient started steroid therapy with a good effect at first. However, after the recurrence of the disease, the patient was qualified to intensify the immunosuppressive treatment. CONCLUSIONS: In the described case, the intensive diagnostic process and the thorough analysis of the test results relatively quickly led to the correct diagnosis. This enabled the implementation of appropriate treatment and prevented the initiation of empirical therapy for the originally diagnosed Hodgkin's lymphoma.

Serum neurofilament light chain is not a useful biomarker of central nervous system involvement in women with Fabry disease.

Neurofilament Light Chain (NfL) serum concentration is a new noninvasive marker of neurodegenerative disorders. Fabry disease (FD) leads to accumulation of glycosphingolipids in tissues leading to progressive damage of critical body systems and organs, including peripheral and central nervous system. There are no established serum markers of neurodegeneration in FD. Our cross-sectional single-center study was designed to prove the concept that serum NfL levels could reflect the severity of cognitive impairment and indirectly, the level of central nervous system involvement in women at earlier stages of FD. Twelve women with a diagnosis of FD confirmed by genetic tests and 12 matched healthy subjects were included. Serum concentrations of NfL were measured in all subjects together with neuropsychological tests that included Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA). Quality of life was assessed with the Short Form Survey (SF-36). FD patients and healthy subjects did not differ with respect to serum NfL concentration, results of neuropsychological tests and quality of life. There was a significant positive correlation between NfL and globotriaosylosphingosine (lyso-Gb3) concentration in women with FD (R = 0,69, p = 0.01). There was also a correlation between NfL concentration and MoCA score but not MMSE score. Receiver operating characteristic (ROC) analysis showed that the best predictor for Mild Cognitive Impairment in both groups was eGFR. Serum NfL concentration does not appear to predict the degree of nervous system involvement in women with FD.

First two years of reimbursed enzyme replacement therapy in the treatment of Fabry disease in Poland.

Fabry disease (FD) is an ultra-rare genetic lysosomal storage disease caused by pathologic gene variants resulting in insufficient expression of α-galactosidase A. This enzyme deficiency leads to accumulation of globotriaosylceramide and globotriaosylsphingosine in plasma and in different cells throughout the body, causing major cardiovascular, renal, and nervous system complications. Until 2018, reimbursed enzyme replacement therapy (ERT) for FD was available in all European Union countries except Poland.             We present the preliminary results of the first two years of reimbursed ERT in Poland. We obtained data from the seven largest academic centers in Katowice, Kraków, Wroclaw, Poznan, Gdansk, Warszawa, and Lódz. The questionnaire included the following data: number of patients treated, number of patients qualified for ERT, and patient characteristics.             All centers returned completed questionnaires that included data for a total of 71 patients (28 men and 43 women) as of June 2021. Thirty-five patients with the diagnosis of FD confirmed by genetic testing (22 men and 13 women) had already qualified for reimbursed ERT. Mean (SD) age at the commencement of the ERT program was 39.6 (15.5) years (range 18-79 years). Mean time from the first clinical symptoms reported by the patients to the FD diagnosis was 21.1 (8.9) years, and the mean time from the final diagnosis of FD to the beginning of ERT was 4.7 (4.6) years.             FD is still underdiagnosed in Poland. To identify undiagnosed FD patients and to ensure that patients in Poland benefit fully from ERT, implementation of an effective nationwide screening strategy and close cooperation with a network of rare disease centers is advised.

Idiopathic Spontaneous Rupture of Renal Pelvis in a Single Functioning Kidney.

Spontaneous rupture of renal pelvis (SRRP) is a rare condition resulting in an extravasation of urine into retroperitoneal space. Due to the uncharacteristic symptoms, often mimicking renal colic, its diagnosis may be complicated. Herein, we report a case of a 73-year-old male with a solitary functioning kidney who presented with malaise and right-sided abdominal pain, rapidly followed by anuria. Laboratory tests showed the signs of AKI. Contrast-enhanced CT performed soon after the admission showed nonspecific abnormalities in the right middle abdomen suspected to be either inflammatory infiltration or surgical scarring. Symptomatic treatment was started, and an acute hemodialysis treatment was commenced. After a temporal improvement, the patient's general condition worsened significantly, with exacerbated pain and massive increase in plasma creatinine. A second contrast-enhanced CT was performed with an addition of urography phase, revealing the extravasation of the contrast media in the location suggesting the rupture of the renal pelvis. The patient was treated successfully by the placement of a double-J ureteral stent into the ureter. Usually, a clear etiology of SRRP can be determined, that is, urinary tract obstruction, but in this case, we could not find a definite cause. It is important to remember that in the presence of a nonspecific abdominal pain and laboratory signs of AKI, a rare cause like SRRP should be taken into consideration. Performing a contrast CT scan with urography phase can save time in establishing a diagnosis and enable immediate urological intervention.

Secondary Hemophagocytic Lymphohistiocytosis Complicated by a Cavitary Lung Lesion in a Kidney Transplant Recipient.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon life-threatening condition caused by an uncontrolled immunological response. It can develop secondary to malignancies, infections, systemic diseases, and immunosuppression. Multiple risk factors may present in kidney transplant recipients; however, the cases of HLH in this population have been described sparsely. We report a case of a 39-year-old female kidney transplant recipient who presented to the hospital nearly 3.5 years after the transplantation with general malaise, recent history of weight loss, fevers, and persistent anemia. Laboratory tests showed pancytopenia, hyperferritinemia, hypertriglyceridemia, and increased activity of lactate dehydrogenase. A bone marrow aspiration revealed hemophagocytosis, which led to the diagnosis of HLH. Therapy consisting of high-dose steroids and plasma exchanges was administered, resulting in a significant improvement of blood count parameters and the patient's general condition. While searching for the triggering disease, a single cavitary lesion in the right lung was revealed in a chest radiograph. Computed tomography scan, bronchoscopy, and additional laboratory testing did not reveal a definitive cause of the lesion. We suspect that the lesion may be a consequence of HLH. The patient was disqualified from thoracic surgery due to multiple comorbidities. Even though HLH is a rare condition, it should be taken into consideration in a kidney transplant patient presenting with unspecific symptoms accompanied by a bicytopenia. It has an unpredictable course that often results in serious complications. Thus close follow-up of the patient and a wide array of imaging and laboratory tests remain crucial.

Effects of a Structured Physical Activity Program on Serum Adipokines and Markers of Inflammation and Volume Overload in Kidney Transplant Recipients.

BACKGROUND Kidney transplantation (KTx) reverses most abnormalities related to chronic kidney disease (CKD), but sedentary lifestyle persists in most kidney graft recipients. Physical inactivity has been associated with altered adipokine profile and inflammation in CKD. We postulated that increased physical activity achieved through an individually-tailored program can reverse these changes. MATERIAL AND METHODS We included 25 clinically stable KTx recipients at least 12 months after transplantation and with eGFR >30 mL/min and 15 age-matched non-dialysis patients with CKD stage 3. Body composition, pattern of daily physical activity, and serum concentrations of leptin, adiponectin, NT-proBNP, and hsCRP were assessed at baseline. All patients in both groups participated in a 12-week supervised exercise program with short cell phone text reminders. All measurements were repeated after 3 months. RESULTS Active energy expenditure increased significantly during the 3 months in both the KTx and CKD patients, compared with baseline by 47% (p<0.001) and 20% (p=0.01), respectively. Time spent daily on physical activity was also increased (129±83 vs. 194±142 and 81±56 vs. 124±57 min, respectively, p<0.001). Adipose tissue mass decreased significantly in the KTx group (from 40.8±11 to 38.5±10.3 kg, p=0.01). Serum leptin decreased significantly in both KTx and CKD patients (from 11.5±7.0 to 10.0±5.6, p=0.03 and from 14.1±8.3 to 12.2±6.1 ng/mL, p=0.01, respectively). Serum adiponectin increased only in the KTx group (from 1900±953 to 2015±1133 ng/L, p=0.004). Serum CRP decreased in both groups (from 15.1±5.2 to 14.0±5.6 mg/L, p=0.01 in the KTx group and from 16.5±3.9 to 15.4±4.3 mg/L in the CKD group p=0.05). NTpro-BNP was unchanged during the study. CONCLUSIONS Increased physical activity induces beneficial effects on adipokine profile and inflammation but does not seem to affect volume overload in kidney transplant recipients and CKD patients.

Simultaneous Improvement of Habitual Physical Activity and Life Quality in Kidney Transplant Recipients Involved in Structured Physical Activity Program.

OBJECTIVES: The aim of the study was to compare the effects of a physical activity program on daily physical activity and quality of life in kidney transplant (KTx) recipients and in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: The study group consisted of 24 KTx recipients and 15 patients with stage 3 to 4 CKD. Habitual physical activity was monitored for 72 hours. Individualized structured programs of increased physical activity were prepared based on baseline physical performance. The measurements were repeated after 1 and 3 months. Participants completed the 36-item Short Form Health Survey questionnaire and an International Physical Activity Questionnaire at baseline and after 1, 2, and 3 months. RESULTS: Physical activity duration and total energy expenditure significantly increased after 3 months in both KTx recipients (from 126 ± 87 to 200 ± 132 min/d, P = .001, and from 1.73 ± 0.37 to 2.24 ± 0.59 cal/min, P < .001, respectively) and CKD patients (from 79 ± 78 to 129 ± 114 min/d, P < .001, and from 1.5 ± 0.5 to 1.92 ± 0.47 cal/min, P < .001, respectively). Short Form Health Survey total score and physical component scale score improved significantly in both groups. Mental component scale score increased significantly only in KTx patients. CONCLUSION: Increased physical activity induces similar beneficial effects on total and physical activity component of quality of life and habitual daily activity in CKD and KTx patients.

Associations Between Intravenous Iron, Inflammation and FGF23 in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5.

BACKGROUND/AIMS: Both iron deficiency and chronic inflammation are highly prevalent in patients with chronic kidney disease (CKD). The effect of intravenous iron infusion on mineral metabolism in CKD may be modified by inflammation. Intravenous iron theraphy may reduce peripheral degradation, secretion, clearence of iFGF23 and lead to hypophosphatemia. The aim of the study was to evaluate the effect of intravenous iron on mineral metabolism in CKD patients. METHODS: 35 non-dialysis patients with CKD stages 3-5. received 100 mg/24h of ferric oxide saccharated solution for 5 days. Serum calcium (Ca), phosphorus (P), parathormone (PTH), intact-FGF23 (iFGF23), C-terminal-FGF23 (cFGF23), bone alkaline phosphatase (BAP) and high-sensitive CRP were assessed on day 1 and 3 at baseline and 2 hours after each dose administration and once on day 6. Plasma iFGF23 and cFGF23, as well as serum BAP were measured with ELISA and other parameters with standard automated laboratory methods. RESULTS: Serum iFGF23 increased after iv iron on day 1 and 6 (from 268.9±446.5 to 326.3±529.9 on day 1; p=0.05 and to 451.4±601 pg/mL on day 6; p=0.03). cFGF23 was reduced only on day 1 (from 654.3±441.3 to 473.6±414 RU/mL; p=0.016). P concentration decreased significantly two hours after the first iron infusion (from 1.69±0.5 to 1.54±0.35 mmol/l; p=0.003). In following days the changes of cFGF23, P and of other calcium-phosphate metabolism were not significant. Serum CRP correlated neither with iFGF-23 nor cFGF-23. CONCLUSION: Intravenous iron supplementation may only transiently affect the production and degradation of FGF23 resulting in hypophosphatemia at the commencement of iron therapy. Chronic low-grade inflammation does not seem to play a role in that mechanism.