Is C1q nephropathy associated with a WDR19 gene mutation? A case report.

BACKGROUND: Even though complement 1q nephropathy (C1qN) was first introduced in 1985, this entity is still unknown and recognized by clinicians due to its rare prevalence (0.2 - 2.5 %) and insufficient emphasis. DESCRIPTION OF THE CASE: A 50-year-old woman was incidentally found to have non-nephrotic proteinuria with a normal glomerular filtration rate. Renal biopsy revealed C1qN with severe fibrosis. The presence of consanguinity and kidney diseases in family members of the patient led to genetic research, and homogenous mutation of c.991G>T (p.G331C) in the WD-repeat domain 19 (WDR19) gene was found. The same homozygous and heterozygous mutations in the WDR gene were found in the relatives of our patient with kidney diseases. One year of follow-up with methylprednisolone and mycophenolate mofetil treatment resulted in partial remission of the kidney disease. CONCLUSION: Renal biopsy for patients with non-nephrotic proteinuria without delay is suggested as it might be a surrogate marker of severe injury. Genetic mutations in the WDR19 gene should be searched for C1qN pathogenesis. This is the first adult case report on C1qN from Turkey.HIPPOKRATIA 2021, 25 (2):87-90.

Deactivation of cardiovascular implantable electronic devices in patients nearing end of life : Reality or only recommendation?

BACKGROUND: Current guidelines recommend considering deactivation of cardiac implantable electronic devices (CIEDs) in patients nearing death. We evaluated the implementation of this recommendation in unselected deceased individuals with CIEDs. METHODS: Over a 7-month period in 2016, all deceased persons taken to the Rostock crematorium were prospectively screened for CIEDs and these were interrogated in situ. Pacing rate, pacing mode, and lead output were documented as well as patient data including location and time of death. In implantable cardioverter-defibrillators (ICDs), tachycardia therapy adjustment and occurrence of shocks 24 h prior to death were also recorded. RESULTS: We examined 2297 subjects, of whom 154 (6.7%) had CIEDs. Of these subjects, 125 (100%) pacemakers (PMs) and 27 (96.4%) ICDs were eligible for analysis. Death in persons with ICDs occurred most frequently in hospital (55.6%), while this was less frequently the case for individuals with PMs (43.2%). Furthermore, 33.3% of subjects with ICDs and 18.5% with PMs died in palliative care units (PCU). Shock therapies were switched off in three (60%) individuals with ICDs who died in the PCU, whereas antibradycardia therapy was not withdrawn in any PM patient in the PCU. Therapy withdrawal occurred in two patients with PMs (1.3%) who died in hospital. Patients with PMs had high ventricular pacing rates at the last interrogation (69 ± 36.0%) and often suffered atrioventricular block (39.2%). Six (25%) of the 24 active ICDs presented shocks near the time of death. CONCLUSION: Many CIED patients died in hospital; nonetheless, in practice, CIED deactivation near death is rarely performed and might be less feasible in subjects with PMs. However, there is still a need to consider deactivation, especially in individuals with ICDs, as one fourth of them received at least one shock within 24 h prior to death.

Individual programming of current multiprogrammable pacemakers : Still unsatisfactory?

BACKGROUND: Pacemaker (PM) technology has developed tremendously in recent decades. We evaluated the extent of individual programming in current PMs. METHODS: Over a 7-month period in 2016, all deceased persons taken to the Rostock crematorium were prospectively screened for cardiac implantable electronic devices (CIEDs) and these were interrogated in situ. Programming of patient data, leads, and study parameters including mode, lower rate, upper tracking or sensor rate (UTSR), ventricular refractory time, sleeping function, hysteresis, and PM-mediated tachycardia intervention were analyzed and compared with delivery settings. Alterations in atrial/ventricular capture management and atrial/ventricular sensing assurance as well as changes in sensitivity and lead output were evaluated. RESULTS: We examined 2297 subjects, of whom 154 (6.7%) had CIEDs, with 125 (81.2%) being PMs. Finally, 72 (57.6%) PMs were eligible for analysis with an operation time of 31.0 ± 27.0 months. We excluded 28 (18.2%) implantable cardioverter defibrillators (ICDs), 51 (41%) PMs presenting elective replacement indicator (ERI), two (1.6%) PMs with programming to insufficient function prior to death, and the left ventricle parameter of one (1.4%) cardiac resynchronization therapy pacemaker (CRT-P); further one CIED (0.6%) was not contactable. PMs offered in mean 75.2% of study parameters thereof 88.0% were to adjust manually, whereof 49.3% stayed unchanged to delivery mode. Lead output, UTSR, lower rate, and mode were the most frequently changed parameters (>85.7%, 65.3%, 54.2%, and 52.8%, respectively) compared with unmodified ventricular refractory time and hysteresis (91.7% and. 85.4%, respectively); 2.8% of PMs had out-of-the-box settings. The most frequent personalized data were last (88.9%) and first name (73.6%), while atrial and ventricular serial lead numbers were rarely entered (18.2% and 23.4%, respectively). CONCLUSION: The programming possibilities of PMs have advanced greatly. Nonetheless, improvements in individual PM programming are still needed as demonstrated by the findings in this study, e.g., PMs with manufacturer settings and lack of individual data.

Hysterosalpingography prior to the gonadotropin stimulated intrauterine insemination improves clinical pregnancy rates in women with unexplained infertility.

PURPOSE OF INVESTIGATION: Gonadotropin stimulated intrauterine insemination (IUI) cycles performed following one month after hysterosalpingography (HSG) are associated with improvement in clinical pregnancy rates in unexplained infertile couples. MATERIALS AND METHODS: A retrospective cohort study was performed between 2008 and 2014. A total of 92 unexplained infertile couples undergoing their first cycle IUI stimulated by gonadotropins were included in the analysis. Participants were classified into two groups according to IUI cycles performed one month (Group A, n = 25 cycles) or longer than one month (Group B, n = 67 cycles) after the HSG procedure. RESULT: The overall clinical pregnancy rate was found as 25% (23 clinical pregnancies / 92 cycles). Clinical pregnancy rate was 44 % (11/25) for Group A and 17.9 % (12/67) for Group B. In Group A, there were significantly higher clinical pregnancy rates compared to Group B (OR: 3.6, 95% CI, 1.3-9.8; p = 0.012). CONCLUSIONS: It has been demonstrated that fertility improving effect of HSG was most prominent in the first six months after procedure. Likewise, in gonadotropin stimulated IUI cycles performed following one month after HSG, there seems to be an improvement in pregnancy rates in unexplained couples. In unexplained cases, it may be a reasonable approach to plan IUI cycles in the first month after HSG in clinical practice.

Generation of improved human cerebral organoids from single copy DYRK1A knockout induced pluripotent stem cells in trisomy 21: hypothetical solutions for neurodevelopmental models and therapeutic alternatives in down syndrome.

Dual-specificity thyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a strong therapeutic target to ameliorate cognitive functions of Down Syndrome (DS). Genetic normalization of Dyrk1a is sufficient to normalize early cortical developmental phenotypes in DS mouse models. Gyrencephalic human neocortical development is more complex than that in lissencephalic mice; hence, cerebral organoids (COs) can be used to model early neurodevelopmental defects of DS. Single copy DYRK1A knockout COs (scDYRK1AKO-COs) can be generated from manipulated DS derived (DS-) induced pluripotent stem cells (iPSCs) and genetic normalization of DYRK1A is expected to result in corrected neurodevelopmental phenotypes that can be reminiscent of normal COs. DYRK1A knock-in (DYRK1AKI) COs can be derived after genetic manipulations of normal iPSCs and would be valuable to evaluate impaired neocortical development as can be seen in DS-COs. DYRK1A mutations cause severe human primary microcephaly; hence, dose optimization studies of DYRK1A inhibitors will be critical for prenatal therapeutic applications in DS. Several doses of DYRK1A inhibitors can be tested in the neurodevelopment process of DS-COs and DS-scDYRK1AKO-COs would be used as optimum models for evaluating phenotypic ameliorations. Overdose drug exposure in DS-COs can be explained by similar defects present in DS-baDYRK1AKO-COs and DYRK1AKO-COs. There are several limitations in the current CO technology, which can be reduced by the generation of vascularized brain-like organoids giving opportunities to mimic late-stage corticogenesis and complete hippocampal development. In the future, improved DS-DYRK1AKO-COs can be efficient in studies that aim to generate efficiently transplantable and implantable neurons for tissue regeneration alternatives in DS individuals.

Importance of Myc-related microRNAs in induced pluripotency.

Pluripotent stem cells (PSCs) have the capacity to differentiate into any cell type of the body. Therefore, induced pluripotent stem cells (iPSCs) are seen as a promising solution for patient-specific cell therapies. However, the safety is major issue for in vitro methods that are used in induction of pluripotency and also in differentiation of PSCs toward specific cell types. In pioneer studies of iPSC generation, the role of c-Myc has been highlighted as a possible master regulator of pluripotency, but direct c-Myc overexpression is known to prompt drawbacks, especially in human cells. In recent studies, the role of non-protein coding RNA molecules such as microRNAs (miRNAs) has been shown in enhanced reprogramming efficiency. In addition, new reprogramming methods have been ultimately improved by adding miRNAs, in the absence of previous factors. Cross interaction between miRNAs and c-Myc has been also found in differentiation of iPSCs, as well as in reprogramming and self-renewing the pluripotent state. Thence, miRNAs are promising solution for efficiency and safety of iPSC derivation and differentiation methods. The purpose of the present review is to evaluate interaction mechanisms of miRNAs with c-Myc and in iPSC technology.

Preventing intraperitoneal adhesions with ethyl pyruvate and hyaluronic acid/carboxymethylcellulose: a comparative study in an experimental model.

OBJECTIVE: To compare the effectiveness of ethyl pyruvate (EP) with that of hyaluronic acid+carboxymethyl cellulose (Seprafilm) for the prevention of intraperitoneal adhesions. Seprafilm has been shown to be effective in many experimental and clinical studies. STUDY DESIGN: Thirty rats were divided into three groups at random, and uterine horn abrasion was performed by laparotomy. One group received no treatment (control group), one group received a single intraperitoneal dose of EP 50mg/kg (EP group), and a 2×1-cm patch of Seprafilm was applied in the third group (Seprafilm group). All rats were killed 14 days after surgery. Macroscopic and histopathological evaluation were performed by a surgeon and a pathologist who were blinded to group allocation. Histopathologically, inflammation, fibroblastic activity, foreign body reaction, collagen proliferation, vascular proliferation, Masson-Trichrome score, matrix metalloproteinase-2 score and vascular endothelial growth factor score were studied. RESULTS: Median macroscopic intraperitoneal adhesion scores for the control, EP and Seprafilm groups were 2.8, 1.2 and 1.1, respectively. Multiple comparisons between groups showed a significant difference (p<0.05). In binary comparisons, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.05). No significant difference was found between the adhesion scores for the EP group and the Seprafilm group (p>0.05). After histopathological evaluation, significant differences in all parameters were found between the groups (p<0.05). In the paired comparison, significant differences were found between the control group and the EP group, and between the control group and the Seprafilm group (p<0.0167), but no significant difference was found between the EP group and the Seprafilm group (p>0.0167). CONCLUSIONS: In comparison with the untreated control group, EP and Seprafilm were found to reduce the formation of intraperitoneal adhesions. No significant difference was found between EP and Seprafilm.

Effects of long-term fasting on female hormone levels: Ramadan model.

BACKGROUND: Ramadan fasting is a special model of hunger and particularly affects metabolic processes, including carbohydrate and lipid levels. Endocrine changes induced by Ramadan fasting are not well known. OBJECTIVE: The aim of this article was to evaluate the changes in hormone levels in women before and after the special Muslim fasting period of Ramadan. MATERIALS AND METHODS: This study was performed in 30 healthy women in Obstetrics and Gynecology department during the Ramadan month of2011. Patients during and after the first menstrual period had menstrual cycles fasting blood samples taken on the same days. Luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, and prolactin (PRL) levels were determined. RESULTS: Before and during fasting LH, FSH, E2, testosterone and PRL levels were not statistically different. CONCLUSION: Despite the limited available studies on these subjects in women, effect of Ramadan fasting on hormone levels were found to be within the normal limits.

A rare complication of vaginal delivery: labial adhesion.

UNLABELLED: Labial adhesions are mostly seen in teenagers and menopausal women, however they may be encountered rarely in the postpartum period. Surgical division under local anesthesia is more effective than topical estrogen. CASE: In this article a young women at the age of 23 years, who gave normal vaginal birth 12 months prior and who had difficulty in coitus because of labial sinechia is reported. During physical examination, an adhesion between right and left labia minora approximately three cm in length was observed. The adhesion was seperated under local anesthesia and the patient was discharged from the hospital on the same day. On postoperative seventh day control, she had neither complaints nor complications. CONCLUSION: Labial adhesions are rarely encountered after normal vaginal childbirth. The most effective treatment of labial sinechia is surgical division under local anesthesia.

[A case of cardiac AA amyloidosis]. / AA-Amyloidose mit kardialer Beteiligung.

HISTORY AND CLINICAL FINDINGS: A 51-year-old woman was referred for kidney transplant evaluation. An HIV infection had been diagnosed ten years ago, viral load being negative at present. Renal type AA-amyloidosis was demonstrated by kidney biopsies. The patient had no symptoms. Clinical examination revealed no significant abnormalities with exception of a systolic murmur. A 12-channel electrocardiogram demonstrated peripheral low voltage. Echocardiography showed severe diastolic dysfunction, ventricular hypertrophy and biatrial dilatation. In addition, the aortic valve displayed a calcified mass. TREATMENT AND COURSE: Treatment with an ACE-inhibitor for diastolic heart failure was continued, and the patient was included into the renal transplantation program. CONCLUSIONS: Amyloidosis is characterized by an abnormal folding of certain proteins and their extracellular deposition in several organs. This leads to corresponding dysfunction and can result in organ failure. Cardiac involvement is usually associated with immunoglobulin-light-chain (AL) - or familial transthyretin-associated (ATTR) - amyloidosis and indicates a poor prognosis. This report demonstrates a rare case of pronounced cardiac manifestation of the amyloid protein A (AA) - amyloidosis.

[Apixaban: pharmacology and action profile]. / Apixaban: Pharmakologie und klinisches Wirkprofil.

Vitamin K antagonists are currently the most frequently used anticoagulants. However, practical limitations of their application, such as variability in dose response, a narrow therapeutic index and numerous drug and dietary interactions, have lead to development of new oral anticoagulants with better efficacy and safety profile. Recent advances included the development of orally active FXa inhibitors rivaroxaban and apixaban. Rivaroxaban received its marketing approval in September 2008. Apixaban has recently been approved for prevention of venous thromboembolism after total hip or knee replacement. This review describes the pharmacological properties of apixaban and discusses the latest findings from clinical trials.

[Natriuretic peptides in the therapy of acute decompensated heart failure]. / Akut dekompensierte Herzinsuffizienz: klinischer Stellenwert einer Therapie mit natriuretischen Peptiden.

Heart failure is the most frequent cause of hospitalization in elderly population. Unlike the therapy of congestive heart failure, there was only a modest progress in the medical treatment for acutely decompensated heart failure over the past several decades. Moreover, current treatment is associated with many limitations in clinical practice. The family of natriuretic peptides consists of several structurally similar polypeptides (ANP, BNP, CNP, urodilatin, DNP). ANP and BNP are the most characterized substances and represent an important compensatory mechanisms in heart failure because of their vasodilatory, natriuretic and antiproliferative effects. Nesiritide is a recombinant human BNP which has been shown to be effective in treating heart failure in several clinical trials. However, a recent meta-analysis revealed a nesiritide-associated increased 30-day-mortality rate. The results of initial small-sized trials suggest beneficial hemodynamic effects of urodilatin in decompensated heart failure. Despite of being approved for the treatment of decompensated heart failure in some countries, the clinical relevance of nesiritide is currently unclear. Urodilatin might represent a potential alternative.

[Treatment of pseudoaneurysms by thrombin injection]. / Perkutane Thrombininjektion bei Aneurysma Spurium.

The incidence of pseudoaneurysms after percutaneus arterial procedures is a quite common complication. Ultrasound-guided thrombin injection is an effective and elegant therapy with a low procedural risk, when the physician is trained in the technique. This paper provides a tutorial for physicians including tips and pitfalls.

[ADP receptor blockers: new insights in the therapy and prophylaxis of ischemic heart disease]. / ADP-Rezeptor-Antagonisten: neue Erkenntnisse zur Therapie und Prophylaxe der ischämischen Herzerkrankung.

Adenosine diphosphate (ADP)-induced platelet activation plays a pivotal role in the thrombocyte aggregation and pathogenesis of ischemic heart disease. The long-term benefit of dual anti-platelet therapy with ADP-receptor antagonists, such as clopidogrel, in combination with aspirin is well established for patients following coronary stent implantation. This review discusses latest developments in the field of ADP-receptor antagonists.

[Hemodynamic monitoring in the intensive care unit: pulmonary artery catheter versus PiCCO]. / Hämodynamisches Monitoring auf der Intensivstation: Pulmonalarterienkatheter versus PiCCO.

Hemodynamic monitoring is essential in the diagnosis and management of critically ill patients. Cardiac output represents a major monitoring parameter. There are a number of methods for measurement of cardiac output with various invasive capacities and functional reliability. Thermodilution pulmonary artery catheter and pulse contour analysis by PiCCO are widely used techniques to measure cardiac output in intensive care unit. This review describes the basic principles, limitations and complications of both monitoring tools.

[Platelet inhibition with prasugrel]. / Hemmung der Thrombozytenaggregation mit Prasugrel.

Platelet activation plays a pivotal role in the pathogenesis of coronary artery disease. The long-term benefit of dual anti-platelet therapy with clopidogrel and aspirin is well established for patients with acute coronary syndrome and for secondary prophylaxis of coronary artery disease. This review discusses latest developments in the field of the thienopyridines. Particularly, we focus on the evidence-based use of prasugrel or prasugrel versus clopidogrel in clinical practice.