A study indicates an essential link between a mild deterioration in excretory kidney function and the risk of neutropenia during cancer chemotherapy.

PURPOSE: Neutropenia, defined as a number of neutrophils in patients' blood specimen lower than 1500 cells/µm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60-89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN. METHODS: The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration. RESULTS: Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45-27.29; p < 0.01). CONCLUSIONS: Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN. Authors are advised to check the author instructions for the journal they are submitting to for word limits and if structural elements like subheadings, citations, or equations are permitted.

Adverse Renal Effects of Anticancer Immunotherapy: A Review.

Modern oncological therapy utilizes various types of immunotherapy. Immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells (CAR-T) therapy, cancer vaccines, tumor-targeting monoclonal antibodies (TT-mAbs), bispecific antibodies and cytokine therapy improve patients' outcomes. However, stimulation of the immune system, beneficial in terms of fighting against cancer, generates the risk of harm to other cells in a patient's body. Kidney damage belongs to the relatively rare adverse events (AEs). Best described, but still, superficially, are renal AEs in patients treated with ICIs. International guidelines issued by the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) cover the management of immune-related adverse events (irAEs) during ICI therapy. There are fewer data concerning real occurrence and possible presentations of renal adverse drug reactions of other immunotherapeutic methods. This implies the need for the collection of safety data during ongoing clinical trials and in the real-life world to characterize the hazard related to the use of new immunotherapies and management of irAEs.

Transplanted kidney loss during colorectal cancer chemotherapy: A case report.

BACKGROUND: The overall risk of de novo malignancies in kidney transplant recipients (KTRs) is higher than that in the general population. It is associated with long-lasting exposure to immunosuppressive agents and impaired oncological vigilance due to chronic kidney disease. Colorectal cancer (CRC), frequently diagnosed in an advanced stage, is one of the most common malignancies in this cohort and is associated with poor prognosis. Still, because of the scarcity of data concerning adjuvant chemotherapy in this group, there are no clear guidelines for the specific management of the CRCs in KTRs. We present a patient who lost her transplanted kidney shortly after initiation of adjuvant chemotherapy for colon cancer. CASE SUMMARY: A 36-year-old woman with a medical history of kidney transplantation (2005) because of end-stage kidney disease, secondary to chronic glomerular nephritis, and long-term immunosuppression was diagnosed with locally advanced pT4AN1BM0 (clinical stage III) colon adenocarcinoma G2. After right hemicolectomy, the patient was qualified to receive adjuvant chemotherapy that consisted of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4). The deterioration of kidney graft function after two cycles caused chemotherapy cessation and initiation of hemodialysis therapy after a few months. Shortly after that, the patient started palliative chemotherapy because of cancer recurrence with intraperitoneal spread. CONCLUSION: Initiation of adjuvant chemotherapy for colon cancer increases the risk of rapid kidney graft loss driven also by under-immunosuppression.

Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.

Neuronal ceroid lipofuscinoses (NCLs) are a group of rare, inherited, neurodegenerative lysosomal storage disorders that affect children and adults. They are traditionally grouped together, based on shared clinical symptoms and pathological ground. To date, 13 autosomal recessive gene variants, as well as one autosomal dominant gene variant, of NCL have been described. These genes encode a variety of proteins, whose functions have not been fully defined; most are lysosomal enzymes, transmembrane proteins of the lysosome, or other organelles. Common symptoms of NCLs include the progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and, in rare adult-onset cases, dementia. Depending on the mutation, these symptoms can vary, with respect to the severity and onset of symptoms by age. Currently, all forms of NCL are fatal, and no curative treatments are available. Herein, we provide an overview to summarize the current knowledge regarding the pathophysiology, genetics, and clinical manifestation of these conditions, as well as the approach to diagnosis.

Stem Cell Therapies for Cerebral Palsy and Autism Spectrum Disorder-A Systematic Review.

Autism spectrum disorder (ASD) and cerebral palsy (CP) are some of the most common neurodevelopmental diseases. They have multifactorial origin, which means that each case may manifest differently from the others. In patients with ASD, symptoms associated with deficits in social communication and characteristic, repetitive types of behaviors or interests are predominant, while in patients with CP, motor disability is diagnosed with accompanying cognitive impairment of various degrees. In order to minimize their adverse effects, it is necessary to promptly diagnose and incorporate appropriate management, which can significantly improve patient quality of life. One of the therapeutic possibilities is stem cell therapy, already known from other branches of medicine, with high hopes for safe and effective treatment of these diseases. Undoubtedly, in the future we will have to face the challenges that will arise due to the still existing gaps in knowledge and the heterogeneity of this group of patients. The purpose of this systematic review is to summarize briefly the latest achievements and advances in stem cell therapy for ASD and CP.

Lyme Neuroborreliosis in Children.

Lyme neuroborreliosis (LNB) is an infectious disease, developing after a tick bite and the dissemination of Borrelia burgdorferi sensu lato spirochetes reach the nervous system. The infection occurs in children and adults but with different clinical courses. Adults complain of radicular pain and paresis, while among the pediatric population, the most common manifestations of LNB are facial nerve palsy and/or subacute meningitis. Moreover, atypical symptoms, such as fatigue, loss of appetite, or mood changes, may also occur. The awareness of the various clinical features existence presented by children with LNB suspicion remains to be of the greatest importance to diagnose and manage the disease.

Cardiac Amyloidosis-Challenging Diagnosis and Unclear Clinical Picture.

Cardiac amyloidosis (CA) is a rare systemic disease determined by the extracellular deposition of amyloid protein in the heart. The protein can accumulate in any part of the heart: myocardium, vessels, endocardium, valves, epicardium and parietal pericardium. The types of CA include the following types: light chain (AL), amyloidosis AA (Amyloid A) and transthyretin (ATTR). The detection of specific subtypes remains of great importance to implement the targeted treatment. We present the case of a 65-year-old woman, who was admitted with severe deterioration of exercise capacity, a bilateral reduction of physiological vesicular murmur, ascites and edema of lower extremities. CA was suspected due to echocardiographic examination results, which led to further examination and final diagnosis. The aim of this study is to improve the disease awareness among clinicians and shorten the delay between the first symptoms and the diagnosis establishment resulting in a better outcome.

Neonatal Seizures Revisited.

Seizures are the most common neurological disorder in newborns and are most prevalent in the neonatal period. They are mostly caused by severe disorders of the central nervous system (CNS). However, they can also be a sign of the immaturity of the infant's brain, which is characterized by the presence of specific factors that increase excitation and reduce inhibition. The most common disorders which result in acute brain damage and can manifest as seizures in neonates include hypoxic-ischemic encephalopathy (HIE), ischemic stroke, intracranial hemorrhage, infections of the CNS as well as electrolyte and biochemical disturbances. The therapeutic management of neonates and the prognosis are different depending on the etiology of the disorders that cause seizures which can lead to death or disability. Therefore, establishing a prompt diagnosis and implementing appropriate treatment are significant, as they can limit adverse long-term effects and improve outcomes. In this review paper, we present the latest reports on the etiology, pathomechanism, clinical symptoms and guidelines for the management of neonates with acute symptomatic seizures.

Infectious complications during immunochemotherapy of post-transplantation lymphoproliferative disease-can we decrease the risk? Two case reports and review of literature.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a heterogeneous group of diseases that develop after solid organ and hematopoietic stem cells transplantation related to intensive immunosuppression regimen, T-cell depletion and Epstein-Barr virus infection. Despite the improvement in the management of PTLD, the prognosis remains poor. Here we report the management of two transplanted patients with PTLD and infections during immunochemotherapy (ICTH). CASE SUMMARY: Of 65-year-old woman 11 years after kidney transplantation (first case) presented with diffuse large B-cell lymphoma (DLBCL) CS III and started ICHT according to R-CHOP protocol. Despite the secondary prevention of neutropenic fever, the patient developed grade 4 neutropenia with urinary and pulmonary tract infections after the fifth cycle. ICTH was continued in reduced doses up to 7 cycles followed by involved-field radiation therapy of the residual disease. The second case presents a 49-year-old man, 8 years after liver transplantation due to cirrhosis in the course of chronic hepatitis B, who started ICTH for DLBCL Burkitt-like CS IV. The patient received four cycles of ICTH according to R-CODOX/R-IVAC protocol, with reduced doses. In both cases initially undertaken reduction of immunosuppression was ineffective to prevent infectious complications. Despite one incomplete ICHT treatment due to recurrent infections, both our patients remain in complete remission. CONCLUSION: Reduction of immunosuppression and the doses of chemotherapeutics may be insufficient to prevent infectious complications during ICTH in PTLD patients.

Successful chemotherapy with liposomal doxorubicin for metastatic Kaposi's sarcoma without skin involvement in the kidney transplant recipient.

Kaposi's sarcoma (KS), one of the most typical malignancies after kidney transplantation, is strongly associated with human herpes virus 8 infection. More than 90% of patients had primary skin changes, which make the diagnosis easier and faster. The lack of skin lesions is considered rare, especially in the iatrogenic type of sarcoma, including patients on immunosuppression and may cause a diagnostic challenge due to the variety of organ involvement, imitating other diseases. The aim of this case presentation is to raise attention to the atypical clinical manifestation of this malignancy. Currently, several different therapeutic options are available for patients with KS, including reduction of immunosuppression, conversion of immunosuppression to mTOR inhibitors, or chemotherapy. Here, we present an unusual case of advanced KS human immunodeficiency virus-negative patient after kidney transplantation without primary skin involvement.