Individual Cases Research Articles

The use of emicizumab in children with hemophilia A without inhibitors in the real-world clinical setting

In our country, the use of emicizumab in children with hemophilia A without inhibitors (HA) in the real-world clinical setting is limited and is available only as few individual case reports. Our aim was to evaluate the effectiveness and safety of the prophylactic use of emicizumab in children with severe HA in the real-world clinical setting. We conducted a retrospective analysis of medical records of children with HA who had received emicizumab at 9 centers based in the Russian Federation. We assessed the annualized bleeding rate (ABR), annualized spontaneous bleeding rate (ASBR), annualized joint bleeding rate (AJBR), annualized bleeding rate for bleeding episodes that required additional treatment with FVIII concentrate (ABRRT) and the number of hospital admissions for bleeding both before and after the treatment with emicizumab, as well as the occurrence and severity of adverse events during the therapy. Ethics committee approval was not required for this study because it involved the use of aggregated retrospective data from routine clinical practice that were fully anonymized. Two emicizumab administration regimens were compared with regard to their effectiveness. Before the treatment with emicizumab, ABR was 5.38 (95% confidence interval (CI) 3.90–7.64), ASBR – 4.16 (95% CI 2.99–5.94), AJBR – 2.7 (95% CI 1.87–4.03), and ABRRT – 4.8 (95% CI 3.37–7.08). After the initiation of the treatment with emicizumab, the bleeding rate plummeted: ABR decreased by 93.9% (95% CI 88.8–96.7), ASBR – by 96.9% (95% CI 93.1–98.6), AJBR – by 96.1% (95% CI 90.4–98.4%) and ABRRT – by 95.1% (95% CI 90.0–97.6). During the treatment with emicizumab, the rate of bleeding episodes that required hospital admission decreased from 1.58 (95% CI 0.98–2.68) to 0.04 (0.01–0.10), which amounted to 97.6% (95% CI 91.1–99.4). The median follow-up time for the patients treated with emicizumab was 15.5 months (range 9–29 months). When comparing the annualized bleeding rates in the groups of the patients who were preventively treated with emicizumab at doses of 3 mg/kg (administered once every 2 weeks) and 1.5 mg/kg (once per week), we didn't find any statistically significant differences. In the real-world clinical setting, the use of emicizumab in the children with HA led to a significant reduction in all bleeding episodes (by more than 90%), regardless of the administration regimen.

Homeopathy for Major Depressive Disorder: protocol for N-of-1 studies (HOMDD-1 Studies)

BACKGROUND. Using the N-of-1 methodology, we will investigate the effectiveness and safety of a standardized homeopathy protocol in treating ten individual cases of major depression. PATIENTS. Women and men at age over 18 years with a diagnosis of a Major Depressive Episode given by a psychiatrist, who have presented a therapeutic response (reduction ≥ 50% of the baseline depression score, kept for at least four weeks) during a prior open homeopathic treatment following the protocol of the sixth edition of the Organon, with or without concomitant use of psychotropic drugs. METHODS. Interventions: individualized homeopathy following the same protocol, administered in a solution containing a globule of the fifty-millesimal potency diluted in 20 ml of 30% alcohol; placebo - a hydroalcoholic solution containing 20 ml of 30% alcohol, in the same posology as the individualized homeopathic medicine. Crossover study: the participant will go through three consecutive treatment blocks, with two random and masked treatment periods (A or B) each, corresponding to homeopathy or placebo. Treatment periods will have two, four, and eight weeks in the first, second, and third blocks, respectively. A clinically significant worsening (characterized by an augmentation in BDI inclusion score ≥ 30%) will result in the termination of participation in the study and resumption of the open treatment. Primary measure: behavior of the score of the Beck-II Depression Inventory (BDI-II), self-evaluated by participants at weeks 0-2-4-8-12-16-20-24-28 and analyzed throughout the study concerning homeopathy and placebo partitions. Secondary measures: score of the Clinical Global Impression Scale; mental and physical health scores assessed by the 12-Item Short-Form Health Survey; participant's blind preference for treatment A or B at each block; clinical worsening and Adverse Events. The participant, assistant physician, evaluator, and statistician will remain blinded for the study treatments until the completion of data analysis from every participant.

Vampires, Revenant Souls, and Objects of Healing

This study searches for the characteristic features of religious healing in three phenomena of the seventeenth and eighteenth centuries: veneration of miraculous images, apparitions from Purgatory, and vampire incidences. All the examples originate from the Czech lands, and all were in some way related to the Catholic renewal or strengthening the Catholic faith in this region. Individual cases have been analyzed with regard to the social relevance of religious remedies, their connection to social problems, and the interaction between the actors involved. The authors draw attention to the link between physical and mental healing and show the key role of local spiritual authorities, especially members of religious orders and parish priests, in spreading practices of spiritual healing. The study reveals that, however theologically sensitive they might have been, the practices analyzed were apparently encouraged by the clergy and the social elites in the local communities, therefore they can hardly be associated only with the so-called popular piety of the rural folk.

Moral Capital as an Element of Successful Transitions

Moral capital is of great importance for both the economic and non-economic well-being of a society. However, moral capital is likely to erode during transitions, especially economic ones. The aim of the work is to determine the mechanisms through which the economic and political transition contributes to the erosion of moral capital, but also which measures can affect the rebuilding of moral capital. Analyzing individual cases, especially in Serbia, we draw general conclusions about the impact of economic and political transition on the decline of moral capital in transition countries. In this paper, we argue that the processes put in motion during economic and political transitions that lead to loss of moral capital are likely to result in a new equilibrium state. This state is characterized by the migration of the bearers of moral capital both to the margins of society and out of society and is highly unlikely to be reversed without a focused intervention by the state and society. We further argue that economic theory could both offer a justification for such an intervention and inform on the most effective way to conduct it. This is because the loss of moral capital can be seen as an instance of market failure in transition, one in which parts of the transitional elite are imposing a negative externality on the rest of society. Internalizing this externality -by making the culprits responsible could make the transition more successful; it would benefit justice and prosperity not only in the current economic transition but also in the future restructuring of the national economy and society. We argue that measures to restore moral capital ought to combine monetary transfers, improvement of institutional framework, and immaterial incentives with the aim of initiating processes that could benefit the whole society. Legally required monetary transfers should repair direct damage caused by corrupt actions, but should not benefit any particular individual, while immaterial incentives should be initiated both by the state and the wider society. We found out that activities of transition elites contribute to negative externalities, such as deterioration of moral capital, which results in less social and economic well-being. Additionally, we propose measures which can contribute to the internalization of these externalities.

Педагогические кейсы в системе высшего образования

Introduction. In the system of domestic higher education, the creation of individual cases on pedagogical situations in higher education, and then the formation of their base is in demand. The purpose of the study is to develop a version of the pedagogical case on the situation in the system of higher education as a model for creating a bank of similar cases in the future. Theoretical analysis. When teaching disciplines in the field of higher education for future teachers, cases on various pedagogical situations are used. At the same time, publications on pedagogy consider professional trainings and similar cases on certain situations in preschool and school education, but cases on pedagogical situations that arise in the process of university educational activities are not presented in scientific literature. Results and their discussion. The author’s definition of the case is formulated; the case study on the pedagogical situation when an exam on a discipline is taken ahead of schedule is proposed in the basic and extended version and its solution based on the legislative framework, life and pedagogical experience of the author is given. Conclusion. The formation of the bank of cases on pedagogical situations that characterize the educational process in higher education is only at the initial stage. They have to be worked out and improved in the context of the transformation of higher education in order to effectively solve the problems facing the national higher school today.

Unraveling the Natural History of Good’s Syndrome: A Progressive Adult Combined Immunodeficiency

Good's syndrome (GS) is a rare immune deficiency described almost 6 decades ago. Despite numerous published individual case reports and data collected in cross-sectional studies of small cohorts, the natural history and long-term outcomes of this disease remain unknown. We aimed to determine the clinical and laboratory evolution of 8 adults diagnosed with GS and consecutively evaluated between 1983 and2023. In this prospective, longitudinal cohort study, newly diagnosed patients with GS were followed through repeated measures of clinical, immune, and hematologic changes, as well as targeted genetic screening. All patients reported a healthy childhood and adolescence with symptom onset during the third or fourth decade of life. All presented to our center with recurrent bacterial sinopulmonary infections, thymoma, hypogammaglobulinemia, and absence of B cells. The median age of GS diagnosis was 57 years. During follow-up, immunoglobin replacement therapy effectively minimized sinopulmonary infections. However, the majority experienced severe and systemic viral or fungal infections, 3 developed basal cell carcinomas, and 5 had progressive bronchiectasis and persistent splenomegaly. The most notable clinical feature was opportunistic infections and invitro evidence of cellular immune deficiency, which resulted in the death of 2 individuals. We also report a statistically significant, multidecade progressive decline in lymphocytes, platelets, hemoglobin, and red blood cells in our cohort, suggesting gradual bone marrow failure. Knowledge of the unique phenotype and temporal evolution of GS has allowed us to develop a more comprehensive diagnostic framework. It can be investigated as part of broader research into disease pathophysiology.

Child Fatality Individual Case Reports: A 24‐Year National State‐by‐State Review

AbstractThis study focused on the content of 1186 Child Fatality Review Board individual case reports collected nationally over a 24‐year period (1995–2019). This information, in contrast to group data, may yield important insights into the causative factors, especially for child fatality resulting from neglect and inflicted injury. The reports were collected from six of the 50 states and evaluated for the quality and amount of information. They were also surveyed for data identifying causative factors for neglect and inflicted injury. Only 25 (2 per cent) of 1186 reports that are publicly available contained sufficient information about the four major causative factors—cause of death, prior child protection agency involvement by the family, evidence of professional negligence or error and family history of at‐risk circumstances. The 25 cases were then reviewed and coded for presence of information about these factors. The findings demonstrate the need for federal intervention to provide specific guidelines for the states to track their cases, to use a common nomenclature, to investigate common causative factors and to practice common reporting procedures. In this way, a robust national database can be developed.

Evaluation of humoral immune responses of experimental animals to the recombinant SARS-CoV-2 spike ectodomain with the ISCOM adjuvant

Scientific relevance. The use of recombinant antigens in vaccine production is limited because vaccines based on such antigens tend to have low immunogenicity. However, a COVID-19 vaccine that combines recombinant SARS-CoV-2 spike glycoprotein as its antigen and virus-like immune-stimulating complexes (ISCOMs) as its adjuvant (Nuvaxovid) induces a protective virus-neutralising response. The State Research Center of Virology and Biotechnology “Vector” (hereinafter, Vector) has developed the ISCOM adjuvant Matrix-V, which plays a key role in inducing virus-neutralising antibodies. Studying Matrix-V will provide for the wide use of recombinant antigens combined with this adjuvant in the development and production of novel Russian vaccines.Aim. This study aimed to evaluate the humoral immune responses of experimental animals to intramuscular injections of a complex combining the recombinant Wuhan-type SARS-CoV-2 spike RBD antigen and the virus-like ISCOM adjuvant containing Quillaja saponaria saponins.Materials and methods. The Matrix-V ISCOM adjuvant was produced using Vector’s proprietary technology, which involves cross-flow filtration through Sartorius VivaFlow cassettes. To determine the saponin and residual detergent concentrations in Matrix-V, the authors conducted high-performance liquid chromatography. Having produced the recombinant SARS-CoV-2 RBD antigen, the authors used electron microscopy to analyse the ultrastructure of the ISCOM–antigen complex. In the study of the ISCOM–antigen complex, 25 female Balb/c mice (5 groups) and 15 male and female outbred guinea pigs (3 groups) received two intramuscular injections with a 14-day interval. Serum tests relied on virus neutralisation (VN) and enzyme-linked immunosorbent assay (ELISA) methods and used antigens of 8 SARS-CoV-2 variants (State Collection of Viruses and Rickettsia, Vector). The authors used Statistica 10 to analyse the results.Results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) alone did not induce statistically significant virus-neutralising antibody responses, as shown by the VN results. Two injections of the SARS-CoV-2 RBD antigen (mice: 7 μg, guinea pigs: 1 μg) adjuvanted with Matrix-V (25 μg) resulted in geometric mean antibody titres of 1:83–1:178 (mice) and 1:174–1:587 (guinea pigs) in the VN tests with the Wuhan variant. One injection of the antigen (1 μg or 7 μg) with Matrix-V (25 μg) induced antibodies only in individual cases, as demonstrated by the VN and/or ELISA results. The most intensive immune response was observed in ELISA tests with the Delta variant after two injections of the Ecto-S-Wuhan (1 μg) and Matrix-V (25 μg) complex. Immune responses did not differ between the group that received two injections of the Ecto-S-Wuhan antigen (1 μg) without the ISCOM adjuvant and the negative control group (titres below 1:100; p=0.95). Two injections of the SARS-CoV-2 RBD antigen (7 μg) without the ISCOM adjuvant induced antibodies in mice (titres between 1:248 and 1:1477).Conclusions. Two intramuscular injections of the complex containing the recombinant SARS-CoV-2 RBD antigen and the Matrix-V ISCOM adjuvant induce virus-neutralising antibodies. The approach proposed by the authors has the potential for use in the development of immunobiological medicinal products to prevent and treat a wide range of infectious diseases.

Major in-hospital complications after catheter ablation of cardiac arrhythmias: individual case analysis of 43 031 procedures.

In-hospital complications of catheter ablation for atrial fibrillation (AF), atrial flutter (AFL), and ventricular tachycardia (VT) may be overestimated by analyses of administrative data. We determined the incidences of in-hospital mortality, major bleeding, and stroke around AF, AFL, and VT ablations in four German tertiary centres between 2005 and 2020. All cases were coded by the G-DRG- and OPS-systems. Uniform code search terms were applied defining both the types of ablations for AF, AFL, and VT and the occurrence of major adverse events including femoral vascular complications, iatrogenic tamponade, stroke, and in-hospital death. Importantly, all complications were individually reviewed based on patient-level source records. Overall, 43 031 ablations were analysed (30 361 AF; 9364 AFL; 3306 VT). The number of ablations/year more than doubled from 2005 (n = 1569) to 2020 (n = 3317) with 3 times and 2.5 times more AF and VT ablations in 2020 (n = 2404 and n = 301, respectively) as compared to 2005 (n = 817 and n = 120, respectively), but a rather stable number of AFL ablations (n = 554 vs. n = 612). Major peri-procedural complications occurred in 594 (1.4%) patients. Complication rates were 1.1% (n = 325) for AF, 1.0% (n = 95) for AFL, and 5.3% (n = 175) for VT. With an increase in complex AF/VT procedures, the overall complication rate significantly increased (0.76% in 2005 vs. 1.81% in 2020; P = 0.004); but remained low over time. Following patient-adjudication, all in-hospital cardiac tamponades (0.7%) and strokes (0.2%) were related to ablation. Major femoral vascular complications requiring surgical intervention occurred in 0.4% of all patients. The in-hospital mortality rate adjudicated to be ablation-related was lower than the coded mortality rate: AF: 0.03% vs. 0.04%; AFL: 0.04% vs. 0.14%; VT: 0.42% vs. 1.48%. Major adverse events are low and comparable after catheter ablation for AFL and AF (∼1.0%), whereas they are five times higher for VT ablations. In the presence of an increase in complex ablation procedures, a moderate but significant increase in overall complications from 2005-20 was observed. Individual case analysis demonstrated a lower than coded ablation-related in-hospital mortality. This highlights the importance of individual case adjudication when analysing administrative data.

Closed-loop Functional Electrical Stimulation (FES) – cycling rehabilitation with phase control Fuzzy Logic for fatigue reduction control strategies for stroke patients

Functional Electrical Stimulation (FES) cycling, or FES-Cycling, holds great therapeutic potential for individuals with paralysis, such as those with Spinal Cord Injury (SCI), traumatic brain injury, or stroke, aiming to restore mobility. However, the nonlinear nature of the musculoskeletal system poses a significant challenge in controlling FES-Cycling. To address this, an integrated closed-loop phase angle fuzzy-based system was developed. This system offers real-time control by adjusting stimulation intensity (pulse width) within the range of 50 to 200μs while maintaining a constant frequency of 35Hz, thereby ensuring precise pedaling trajectory and cadence patterns. An experimental study involved three healthy individuals (Cases A, B, and C) and one individual with hemiplegia stroke (Case D). Results showed that the proposed system consistently reduced average angle trajectory errors for Cases A, B, and C, with values of 2.6945, 3.2958, and 2.9922 degrees, respectively. Case D, affected by hemiplegia stroke, faced greater challenges and exhibited a higher error of 3.4562 degrees. Fatigue resistance, evaluated through fatigue indices, showed promising results for Cases A, B, and C with values of 0.10778, 0.06866, and 0.04603, respectively. However, Case D experienced higher fatigue (0.2304) due to the unique challenges of hemiplegia stroke. These findings highlight the effectiveness of the proposed control system in optimizing FES-Cycling, particularly for healthy individuals. For individuals with paralysis, like Case D, further research is needed to adapt the system to their specific conditions and cycling patterns. This system holds the potential for enhancing FES-Cycling as a therapeutic strategy and warrants additional investigation and customization for different patient populations.

Verbalization of the Lexeme «LOVE» in Modern Animated Films

The article discusses the verbalization of the lexeme «LOVE» in modern animated films of American production at the beginning of the XXI century (family and adventure genre). 
 In the theoretical part, lexicographic interpretations of love given in Russian and English dictionaries were presented, the study of this concept in the works of S.G. Vorkachev was considered, and a working definition of love as a feeling of deep sympathy or attachment to animate and inanimate objects was formulated.
 In the practical part of the study, 121 examples were identified and analyzed that maximally verbalize the lexeme «LOVE» in the monologue and cartoon characters' dialogical speech.
 As a result of the study, it was revealed that the feeling of deep attachment manifests itself in subject-subject relationships (in the family, between partners, friends, colleagues, fans, as well as to oneself) and subject-object relationships (to pets, actions, states, place of stay). Individual cases of love have been identified as destructive.
 A percentage analysis of the frequency of use of the lexical unit «LOVE»
 has established the leading position of the manifestation of a sense of deep affection in family relationships. This is followed by partner love, love for pets, objects,
 friendly love, love for states, for the place of stay, for actions, destructive love.
 The least number of examples fell on fanatical and selfish love.
 Thus, the manifestation of a sense of deep affection and sympathy between
 all family members is the main indicator of the strong and positive emotional and
 mental states of the American nation.

Resorbable magnesium metal membrane for sinus lift procedures: a case series

BackgroundThe purpose of this case series was to demonstrate the use of a magnesium membrane for repairing the perforated membrane in both direct and indirect approaches, as well as its application in instances where there has been a tear of the Schneiderian membrane.Case presentationThe case series included four individual cases, each demonstrating the application of a magnesium membrane followed by bone augmentation using a mixture of xenograft and allograft material in the sinus cavity. In the first three cases, rupture of Schneiderian membrane occurred as a result of tooth extraction, positioning of the dental implant, or as a complication during the procedure. In the fourth case, Schneiderian membrane was perforated as a result of the need to aspirate a polyp in the maxillary sinus. In case one, 10 mm of newly formed bone is visible four months after graft placement. Other cases showed between 15 and 20 mm of newly formed alveolar bone. No residual magnesium membrane was seen on clinical inspection. The vertical and horizontal augmentations proved stable and the dental implants were placed in the previously grafted sites.ConclusionWithin the limitations of this case series, postoperative clinical examination, and panoramic and CBCT images demonstrated that resorbable magnesium membrane is a viable material for sinus lift and Schneiderian membrane repair. The case series showed successful healing and formation of new alveolar bone with separation of the oral cavity and maxillary sinus in four patients.

Congenital anomalies of the kidneys and urinary tract (CAKUT) : Embryology in radiology and fetal magnetic resonance imaging

Congenital anomalies of the kidney and urinary tract (CAKUT) are very common findings in fetal diagnostics. Their effects range from variants without pathological significance to pronounced functional impairment with the need for renal replacement therapy in childhood. Sometimes the genital organs are also affected. The aim of the article is to provide an overview of embryology and examples of key findings. In the fetal period, magnetic resonance imaging (MRI) is used, while postnatally, sonography with the option of contrast-enhanced micturition urosonography (MUS, ceVUS) dominates imaging in pediatric radiology, supplemented in individual cases by fluoroscopy (micturition cysturethrography) and MRI. Quantitative methods for assessing kidney function and excretion (MAG3 scintigraphy, functional MR urography) are essential when planning further therapeutic procedures, especially in obstructive uropathies. Imaging plays an essential role in the assessment of abnormalities of the kidneys and urinary tract both pre- and postnatally. Knowledge of embryology facilitates anatomical understanding and assessment of pathologies.

DAPD Set of Pd-Containing Diatomic Molecules: Accurate Molecular Properties and the Great Lengths to Obtain Them.

In the present study, we obtained reliable bond energy, bond length, and zero-point vibrational frequency for a set of diatomic Pd species (the DAPD set). It includes PdH, Pd2, and PdX (X = B, C, N, O, F, Al, Si, P, S, and Cl). Our highest-level protocol (W4X-L) represents scalar and spin-orbit relativistic, valence- and inner-valence correlated, extrapolated CCSDTQ(5) energy. The DAPD set of molecules is challenging for computational chemistry methods in different manners; for Pd2, the spin-orbit contribution to the bond energy is fairly large, whereas for PdC and PdSi, the post-CCSD(T) correlation components are considerable. The diverse range of requirements represents a significant challenge for lower-level methods. While density functional theory (DFT) methods generally yield good agreements for bond lengths and vibrational frequencies, large deviations are found for bond energies. In general, hybrid DFT methods are more accurate than nonhybrid functionals, but the agreement in individual cases varies. This illustrates the critical role that new high-quality reference data would play in the continual development of lower-cost methods.

Energy cost optimization through load shifting in a photovoltaic energy-sharing household community

Home energy management systems are essential for the optimization of resources in complex demand scheduling problems that require energy efficiency in homes. This can be achieved through the use of Renewable Electricity Sources (RES), for cleaner and more sustainable energy generation, as well as participation in Demand Response (DR) programs, for lower energy prices. The problem becomes more complex when it is considered a community of households. This paper aims to address individual and community household participation in DR programs and RES sharing while considering constraints imposed on the operation schedule of appliances, through load shifting optimization. For that, a Genetic Algorithm is proposed, implemented, and validated, which focuses on minimizing energy costs. It takes into account dynamic pricing, distributed generation, and household community energy sharing. Using real household workload data, two case studies are presented, one for the cost optimization of an individual household and another for a photovoltaic energy-sharing household community containing twenty houses. Both case studies represent five days of scheduling, where each house can have up to five appliances able to shift. The business as usual costs are 16.74 EUR and 269.99 EUR for the individual and community case studies, respectively. Results show improvements of up to 24.3% (12.67 EUR in the optimized schedule, 4.07 EUR in savings) for the individual case study and 11.8% (238.21 EUR in the optimized schedule, 31.78 EUR in savings) for the household community. In a community, households can expect cost reductions of 1.5%–26.8% when compared to individual scheduling.

Machine learning models reveal how biochar amendment affects soil microbial communities

The biochar amendment plays a vital role in maintaining soil health largely due to its effects on soil microbial communities. However, individual cases and the variability in biochar properties are not sufficient to draw universal conclusions. The present study aimed to reveal how the biochar application affects soil microbial communities. Metadata of 525 ITS and 1288 16S rRNA sequencing samples from previous studies were reanalyzed and machine learning models were applied to explore the dynamics of soil microbial communities under biochar amendment. The results showed that biochar considerably changed the soil bacterial and fungal community composition and enhanced the relative abundances of Acidobacteriota, Firmicutes, Basidiomycota, and Mortierellomycota. Biochar enhanced the robustness of the soil microbial community but decreased the interactions between fungi and bacteria. The random forest model combined with tenfold cross-validation were used to predict biomarkers of biochar response, indicating that potentially beneficial microbes, such as Gemmatimonadetes, Microtrichales, Candidatus_Kaiserbacteria, and Pyrinomonadales, were enriched in the soil with biochar amendment, which promoted plant growth and soil nutrient cycling. In addition, the biochar amendment enhanced the ability of bacteria to biosynthesize and led to an increase in fungal nutrient patterns, resulting in an increase in the abundance and diversity of saprophytic fungi that enhance soil nutrient cycling. The machine learning model more accurately revealed how biochar affected soil microbial community than previous independent studies. Our study provides a basis for guiding the reasonable use of biochar in agricultural soil and minimizing its negative effects on soil microecosystem.Graphical

In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs?

PICO Question In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs or improving the canine inflammatory bowel disease (IBD) activity index (CIBDAI) or the canine chronic enteropathy clinical activity index (CCECAI)? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed One double-blinded randomised control trial. Strength of evidence Moderate. Outcomes reported The outcome of this study identified that no significant differences in remission rates (> 75% decrease in CIBDAI scores) were observed between the prednisone and budesonide groups. Frequency of adverse effects were also similar between the two groups. Conclusion A single study with moderate power of evidence alongside some significant limitations, particularly population size, cannot be used as the sole provider of an answer to the PICO question. As such, further studies with greater power would be required before a definitive assessment of comparative treatment efficacy can be made. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Clinical and Histopathologic Spectrum of Toxic Erythema of Chemotherapy: A Series of 56 Cases From a Single Institution.

Although many individual cases and small series of toxic erythema of chemotherapy (TEC) have been described, the full spectrum of findings is not well understood. To provide a comprehensive review of the clinical and histopathologic features of TEC with an emphasis on novel histopathologic findings. We searched our electronic medical record for "toxic erythema of chemotherapy" or "neutrophilic eccrine hidradenitis." Fifty-six cases meeting clinical and histopathologic criteria were identified. The electronic medical record and accompanying hematoxylin and eosin-stained slides were retrospectively reviewed. The clinical findings were heterogeneous but included classic presentations such as intertriginous eruptions (34%) and acral erythema (25%). The most common histopathologic features were apoptotic keratinocytes (95%), basal vacuolar change (91%), and epithelial dysmaturation (79%). Eccrine squamous syringometaplasia was seen in over half of the cases (33/56; 59%), whereas neutrophilic eccrine hidradenitis was uncommon (16%). Interestingly, many cases showed prominent interstitial histiocytes (55%). Other novel findings included irregular orthohyperkeratosis (23%), irregular epidermal hyperplasia (14%), and acantholysis (9%). As a retrospective study, it is subject to information bias. This is the largest reported series of TEC. In addition to confirming previously reported features, we identify novel histopathologic findings to add to the spectrum of TEC.

Can Civil Courts Save the Climate? Strategic Climate-change Litigation Before Civil Courts

Climate change is an urgent global problem, and national legislatures must enhance their efforts to reduce carbon dioxide emissions drastically. Individuals and NGOs have filed public law actions against national legislators before international courts (prominently the ECHR) and several constitutional courts to allege violations of constitutional and human rights. In a more recent development, civil courts too are being seized with climate‑change litigation. In 2021, a Dutch court ruling on an action by an NGO against the Royal Dutch Shell Group held that Shell is obliged to reduce its CO2 emissions considerably. This judgment, based on the Dutch Civil Code’s general tort regulations, has triggered a wave of similar actions before German courts. Such cases of individual plaintiffs, supported by NGOs, suing private companies for damages or for an immediate reduction of emissions are examples of ‘strategic litigation’ aimed at bringing about broad societal changes beyond the scope of the individual case at hand. The article analyses the political implications, tackles the question of whether general tort law is a suitable instrument to address the climate‑change problem, and discusses how civil courts may handle these cases. Climate change is a complex, multi-stakeholder issue that requires a difficult process of balancing social, legal, and economic interests – which is the task of democratically legitimised parliaments, not primarily a task of courts.

Reliability of retrospective assessment of the age of first menstruation

The age of the first menstruation is one of the indicators for assessing the course of puberty. It is also a sensitive indicator of the economic situation of individual professional groups or societies, and the low average age of menarche is widely recognized as a marker of society’s well-being. The aim of the study was to analyse the reliability of the retrospective method of assessing the age at menarche by comparing the results to the age obtained from continuous research. Data regarding the age at menarche came from longitudinal somatic development and physical fitness studies conducted between 1976 and 2022. In 2022, 47 women were examined. In continuous studies, the prospective method was used in the assessment of the age of first menstruation while in the 2004 and 2022 studies a retrospective method was applied. Only in 4 out of 47 women the age of the first menstruation declared in 2004 and 2022 (the women were 32–34 and 50–52 years old, respectively) was consistent with the one found in continuous studies. In other cases, there was a discrepancy between the age found in continuous studies and self-reported in 2004 or 2022 or between the age stated in 2004 and 2022. Of those women who were present for the 2022 study, 36 had information about the age of first menstruation from continuous studies and the age of menarche in 2004 was given. For this sample the arithmetic mean and the standard deviation of the age at menarche were calculated. It was found that the retrospective method often used in the assessment of the age of the first menstruation is not fully reliable, as the average discrepancy in the assessment ranged from nearly 1 month (0.05 years) to over 2 months (0.19 years) compared to the prospective method. Women surveyed in 2004 determined the age of the first menstruation more accurately compared to statements obtained 18 years later from the same women. This study suggests that long-term memory (LTM) of a significant life event of every woman is unreliable, as indicated by the difference in the declared age of the first menstruation of women examined in 2004 and 2022, which, in individual cases, was up to 3, 4 or 5 years.