A rare cause of steroid-resistant nephrotic syndrome - a case report.

Steroid resistance is a common condition occurring in children with nephrotic syndrome. Until now, over 50 genes involved in steroid-resistant nephrotic syndrome (SRNS) pathogenesis have been identified, among which the most prevalent are NPHS1, NPHS2, CD2AP, and PTPRO. The patterns of inheritance of SRNS are autosomal recessive, autosomal dominant, or mitochondrial, and tissues of those patients show focal segmental glomerulosclerosis (FSGS) signs in histopathological image analysis. We present a case of a 6-year-old girl who was admitted to the pediatric nephrology department due to nephrotic range proteinuria and edema of the lower leg. We started therapy with prednisone at a dose of 45 mg (60 mg/m2), enalapril as a nephroprotection, and antihistamines as an additional treatment. During in-patient treatment, we detected increased blood pressure. Due to persistent proteinuria in spite of 6-week treatment with steroids at the maximal dose, we confirmed disease resistance to steroids. Additionally, FSGS signs were confirmed in kidney biopsy samples. After genetic screening for SRNS and detection of the rare gene mutation NUP93 we reduced prednisone but maintained nephroprotective treatment and administered cyclosporin A. The girl remains currently under the care of nephrologists with normal arterial blood pressure, trace proteinuria in follow-up examination, and normal kidney function. NUP93 mutation is extremely rare; therefore few cases have been described to date. The onset of the symptoms in all pediatric patients appeared before the age of 8 and they developed end stage kidney disease (ESKD). They might manifest symptoms from the other systems.

[Hypertensive crisis in a 3-year-old boy - neurovascular conflict?] / Przelom nadcisnieniowy u 3-letniego chlopca ­ konflikt naczyniowo-nerwowy?

Hypertensive crisis is a sudden rise in blood pressure with accompanying clinical symptoms. The disease is extremely rare in small children and is always a complication of secondary hypertension. CASE REPORT: 3-year-old boy (spontaneous delivery, 37 week of gestation, birth weight 2170g, 10 AS, unremarkable family history) was admitted to a hospital because of weight loss (1.5 kg, i.e. approx. 15% in 6 months), anorexia, abdominal and limb pain and lethargy. On admission, very high blood pressure values (190/150 mm Hg), lean subcutaneous tissue, frequent blinking, height 88 cm (<3c), body weight 9.5 kg (<3c). In additional tests: blood morphology, parameters of renal function, ions, gasometry, catecholamine urinary excretion, steroid profile and daily cortisol profile were within normal limits. Elevated plasma renin activity was found. In imaging studies kidneys, adrenal glands and renal arteries were normal. Normotension was not obtained on two antihypertensive drugs - metoprolol and amlodipine. In angio-CT tortuous right vertebral artery, extending to the left on the anterolateral surface of the medulla oblongata - possible compression of the vessel of the left side of medulla - was found. Diagnosis of neurovascular conflict was made. The patient was consulted by neurosurgeon who declare no possibility of surgical treatment of anomalies. In the treatment, according to the literature, a drug blocking the renin-angiotensin-aldosterone-enalapril system was used, which normalized blood pressure. At the same time, intensive nutritional treatment was used. Resolution of symptoms and weight gain was observed. In further follow-up patients' parents withdrew enalapril lawlessly, which did not lead to recurrent rise in blood pressure. The latter may suggest other, transient cause of hypertensive crisis e.g. intoxication. CONCLUSIONS: Severe hypertension in pediatric patients can give symptoms as weight loss and behavioral disorders. In the diagnostic of hypertensive crisis in children, neuroimaging studies and toxicological tests should be performed.

The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study.

This study aimed to evaluate the usefulness of vanin-1 and periostin in urine as markers of the autoimmune process in kidneys and renal fibrosis in IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN). From a group of 194 patients from the Department of Pediatrics and Nephrology, who were included in the Polish Pediatric Registry of IgAN and IgAVN, we qualified 51 patients (20 with IgAN and 31 with IgAVN) between the ages of 3 and 17, diagnosed based on kidney biopsy, for inclusion in the study. All of the patients received glucocorticosteroids, immunosuppressive drugs, or renoprotective therapy. The control group consisted of 18 healthy individuals. The concentration of vanin was significantly higher in the IgAN and IgAVN groups than in the control group. The concentration of vanin/creatinine correlates positively with the level of IgA and negatively with the serum level of C3 at the end of the observation. Urinary vanin-1 concentration may be useful as a marker of the active autoimmune process in IgAN and IgAVN in children, but the study needs confirmation on a larger group of children, along with evaluation of the dynamics of this marker. Urinary periostin is not a good marker for children with IgAN and IgAVN, especially in stage 1 and 2 CKD.

Covid-19 and Ukrainian Crisis Exponentiates the Need for the Inclusion of Conflict and Disaster Medicine in Medical Curriculum.

Conflict medicine is an age-old branch of medicine which focuses on delivering healthcare services to the injured in the setting of conflicts, wars, disasters, and/or other calamities. The course in its purest form has been traditionally given only in military medical schools while civilian medical students are usually taught parts of the course in other overlapping subjects like surgery, infectious diseases, etc. However, in a crisis situation, civilian doctors are expected to double up as military doctors, which leads to emotional, mental, and physical stress for the civilian doctors along with logistical and organizational challenges. The current Covid-19 pandemic and the Russo-Ukrainian conflict have highlighted once again the emergent need for the implementation of conflict medicine courses in regular medical curricula, so as to make the medical students situation-ready. With our present discussion, we aim to provide a brief overview of the course, its core modules, challenges to its implementation, and possible solutions. We believe that the complex management skills gained by this course are not only useful in conflict scenario but are also valuable in managing day-to-day medical emergencies.

European Countries Step-up Humanitarian and Medical Assistance to Ukraine as the Conflict Continues.

On the 24th of February 2022, the Russian Federation began an unprovoked invasion of Ukraine, marking the biggest military attack in Europe since the second world war. Over 4 million people have fled their homeland within the first month of the war and have triggered a large refugee crisis with impacts far beyond the Ukrainian border. People in the neighboring countries have shown tremendous support by stepping forward to donate food, clothes, medications, money, and other essential supplies. The governments and other regional stakeholders have also been supportive in accommodating and easing regulations for the incoming refugees. Herein, we summarize the humanitarian measures and medical donations that have been made by European countries as they stepped up their efforts to provide refugees with all necessary basic services. We further highlight potential oncoming challenges in Ukraine and the host countries along with relevant solutions to these challenges. The current scenario highlights the need for multi-party and multi-level collaborations (both public and private) to tackle the emerging situation.

War Psychiatry: Identifying and Managing the Neuropsychiatric Consequences of Armed Conflicts.

War refugees and veterans have been known to frequently develop neuropsychiatric conditions including depression, post-traumatic stress disorder (PTSD), and anxiety disorders that tend to leave a long-lasting scar and impact their emotional response system. The shear stress, trauma, and mental breakdown from overnight displacement, family separation, and killing of friends and families cannot be described enough. Victims often require years of mental health support as they struggle with sleep difficulties, recurring memories, anxiety, grief, and anger. Everyone develops their coping mechanism which can involve dependence and long-term addiction to alcohol, drugs, violence, or gambling. The high prevalence of mental health disorders during and after the war indicates an undeniable necessity for screening those in need of treatment. For medical health professionals, it is crucial to identify such vulnerable groups who are prone to developing neuropsychiatric morbidities and associated risk factors. It is pivotal to develop and deploy effective and affordable multi-sectoral collaborative care models and therapy, which primarily depends upon family and primary care physicians in the conflict zones. Herein, we provide a brief overview regarding the identification and management of vulnerable populations, alongside discussing the challenges and possible solutions to the same.

Entosis: From Cell Biology to Clinical Cancer Pathology.

Entosis is a phenomenon, in which one cell enters a second one. New clinico-histopathological studies of entosis prompted us to summarize its significance in cancer. It appears that entosis might be a novel, independent prognostic predictor factor in cancer histopathology. We briefly discuss the biological basis of entosis, followed by a summary of published clinico-histopathological studies on entosis significance in cancer prognosis. The correlation of entosis with cancer prognosis in head and neck squamous cell carcinoma, anal carcinoma, lung adenocarcinoma, pancreatic ductal carcinoma and breast ductal carcinoma, is shown. Numerous entotic figures are associated with a more malignant cancer phenotype and poor prognosis in many cancers. We also showed that some anticancer drugs could induce entosis in cell culture, even as an escape mechanism. Thus, entosis is likely beneficial for survival of malignant cells, i.e., an entotic cell can hide from unfavourable factors in another cell and subsequently leave the host cell remaining intact, leading to failure in therapy or cancer recurrence. Finally, we highlight the potential relationship of cell adhesion with entosis in vitro, based on the model of the BxPc3 cells cultured in full adhesive conditions, comparing them to a commonly used MCF7 semiadhesive model of entosis.