Cariprazine in Psychiatry: A Comprehensive Review of Efficacy, Safety, and Therapeutic Potential.

This article provides a comprehensive review of recent developments regarding a new atypical antipsychotic drug - cariprazine - considering the mechanism of action, efficacy, safety, and promising therapeutic option for various psychiatric disorders, including schizophrenia and bipolar disorder, therapy of addictions, and treatment in the pediatric population. Its distinct pharmacological profile, characterized by partial agonism at dopamine D2 and D3 receptors, as well as serotonin receptors - 5HT1A with a preference for the D3 receptor - sets it apart from other antipsychotics. The unique mechanism of action contributes to cariprazine's positive impact on negative symptoms in schizophrenia and an antidepressant effect. Its relatively low risk of adverse effects, such as sedation, metabolic issues, and hypotension, enhances its tolerability. In bipolar affective disorder, cariprazine exhibits effectiveness in managing both depressive and manic episodes. Ongoing research in pediatric populations suggests potential benefits in schizophrenia, bipolar I disorder, and autism spectrum disorder, but further research is necessary to establish safety and efficacy. Moreover, cariprazine shows promise in addiction therapy, particularly with coexisting psychiatric disorders. Continued research and clinical exploration may discover additional insights, broadening its use in diverse patient populations. This article aims to review the role of cariprazine, a dopamine D2/D3 and serotonin 5-HT1A receptor partial agonist, in the management of psychotic illnesses, including schizophrenia, bipolar disorder, addiction therapy, and pediatric treatment.

Advances in Mood Disorder Pharmacotherapy: Evaluating New Antipsychotics and Mood Stabilizers for Bipolar Disorder and Schizophrenia.

This article provides a narrative review of recent developments in mood-stabilizing drugs, considering their mechanism of action, efficacy, safety, and therapeutic potential in the treatment of mood disorders, particularly bipolar disorder and schizophrenia. The review focuses on the mechanism and clinical aspects of second-generation antipsychotic medications; aripiprazole, classified as a third-generation antipsychotic medication; lamotrigine, as a representative of antiepileptic drugs; and lurasidone, a novel second-generation antipsychotic medication. Moreover, the article refers to one of the newest and most highly effective normothymic drugs, cariprazine. The potential of new mood stabilizer candidates lumateperone and brexpiprazole is also presented. Covered topics include the clinical efficacy of new drugs in reducing manic and depressive symptoms during acute episodes, as well as their role in preventing relapse. In addition, we analyzed the incidence of adverse effects of each drug. Many of the new drugs have strong potential to be beneficial and safe in cases of many comorbidities, as they do not cause many adverse effects and do not require high doses of use. The results underscore the importance of ongoing and future research to better understand the action and efficacy of these mood stabilizers and their implications in the treatment of mood disorders, aiming to achieve euthymia and improve the quality of life of affected patients. In this article, we aim to review current drug treatments for the management of mood disorders, including bipolar disorder and schizophrenia.

Diagnostic Value and Molecular Function of MicroRNAs in Endometrial Diseases: A Systematic Review.

The human endometrium experiences significant cyclic morphological and biochemical changes throughout the menstrual cycle to prepare for embryo implantation. These processes are meticulously regulated by ovarian steroids and various locally expressed genes, encompassing inflammatory reactions, apoptosis, cell proliferation, angiogenesis, differentiation (tissue formation), and tissue remodeling. MicroRNAs (miRNAs) have been recognized as crucial regulators of gene expression, with their altered expression being linked to the onset and progression of various disorders, including cancer. This review examines the expression of miRNAs in the endometrium and their potential regulatory roles under pathological conditions such as endometriosis, recurrent implantation failure and endometrial cancer. Given miRNAs' critical role in maintaining gene expression stability, understanding the regulatory mechanisms of endometrial miRNAs and identifying their specific target genes could pave the way for developing preventive and therapeutic strategies targeting specific genes associated with these reproductive disorders.

Super Bolus: a remedy for a high glycemic index meal in children with type 1 diabetes on insulin pump therapy?-study protocol for a randomized controlled trial.

BACKGROUND: Postprandial hyperglycemia (PPH) is a common clinical problem among patients with type 1 diabetes (T1D), which is related to high glycemic index (h-GI) meals. The main problem is linked to high, sharp glycemic spikes following hypoglycemia after h-GI meal consumption. There is a lack of effective and satisfactory solutions for insulin dose adjustment to cover an h-GI meal. The goal of this research was to determine whether a Super Bolus is an effective strategy to prevent PPH and late hypoglycemia after an h-GI meal compared to a Normal Bolus. METHODS: A total of 72 children aged 10-18 years with T1D for at least 1 year and treated with continuous subcutaneous insulin infusion for more than 3 months will be enrolled in a double-blind, randomized, crossover clinical trial. The participants will eat a h-GI breakfast for the two following days and receive a prandial insulin bolus in the form of a Super Bolus 1 day and a Normal Bolus the next day. The glucose level 90 min after the administration of the prandial bolus will be the primary outcome measure. The secondary endpoints will refer to the glucose levels at 30, 60, 120, 150, and 180 min postprandially, the area under the blood glucose curve within 180 min postprandially, peak glucose level and the time to peak glucose level, glycemic rise, the mean amplitude of glycemic excursions, and the number of hypoglycemia episodes. DISCUSSION: There are still few known clinical studies on this type of bolus. A Super Bolus is defined as a 50% increase in prandial insulin dose compared to the dose calculated based on the individualized patient's insulin-carbohydrate ratio and a simultaneous suspension of basal insulin for 2 h. Our patients reported the best experience with such a combination. A comprehensive and effective solution to this frequent clinical difficulty of PPH after an h-GI meal has not yet been found. The problem is known and important, and the presented solution is innovative and easy to apply in everyday life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04019821.

Continuous glucose monitoring systems in well-controlled children with type 1 diabetes mellitus.

INTRODUCTION: Numerous studies have demonstrated the clinical benefits of using continuous glucose monitoring (CGM) systems among patients with type 1 diabetes (T1D). Aim of the study was to assess the effectiveness of CGM on metabolic control in children with T1D and well-controlled disease prior to the study. MATERIAL AND METHODS: This prospective analysis included 99 children (46 girls) at the median age of 11.23 years and diabetes duration of at least 1 year (median: 5.16 years), generally well controlled metabolically (median HbA1c: 7.0%), and treated with continuous subcutaneous insulin infusion (CSII). The patients had used CGM for at least 150 days. We analysed the participants in subgroups based on baseline HbA1c < 7%, ≥ 7%, age, and sex. RESULTS: Children with baseline HbA1c < 7% were characterized by significantly increased HbA1c after the median of 273 days (217; 320) of CGM usage (6.3% vs. 6.6%, respectively; p = 0.002). No significant change in HbA1c was noted in children with baseline HbA1c ≥ 7% (7.5% vs. 7.4%, respectively; p = 0.191), but 20% of the group reached the target of HbA1c < 7.0%. The analysis of CGM data revealed that no group achieved the CGM targets of good metabolic control. Total daily insulin requirements remained stable in both groups (p = 0.752; p = 0.274), but the amount of basal insulin increased statistically in both groups (p = 0.009; p ≤ 0.001). CONCLUSIONS: The application of CGM provides detailed information concerning glycaemic control and is beneficial in some, but not all, T1D children with good diabetes control.

Serum galectin-3 and galectin-3 binding protein levels in systemic lupus erythematosus and cutaneous lupus erythematosus.

INTRODUCTION: The roles of galectin-3 (Gal-3) and galectin-3 binding protein (G3BP) in systemic lupus erythematosus (SLE) are of ongoing interest, but the data are insufficient due to highly limited available studies. There are no data on cutaneous lupus erythematosus (CLE). AIM: To assess serum Gal-3 and G3BP concentrations in SLE patients with and without LE-specific skin lesions, CLE patients and to correlate levels of proteins with clinical and laboratory parameters. MATERIAL AND METHODS: The study included 71 SLE patients with and without LE-specific skin lesions, 23 CLE patients and 40 controls. Gal-3 and G3BP were measured by specific enzyme-linked immunosorbent assays (ELISA). RESULTS: Serum Gal-3 and G3BP concentrations were significantly higher in SLE with and without LE-specific lesions compared to controls, but without differences between SLE groups. Gal-3 and G3BP levels were also elevated in CLE compared to controls (p = 0.001, p = 0.005; respectively). There was a positive correlation between G3BP level and CLASI activity score both in CLE (r = 0.55, p = 0.006) and in SLE patients with LE-specific lesions (r = 0.36, p = 0.02). G3BP and Gal-3 levels did not differ in SLE with LE-specific lesions and CLE. There was a positive correlation between serum G3BP level and the SLEDAI score in SLE patients (r = 0.26, p = 0.03). CONCLUSIONS: Our findings indicate that serum G3BP and Gal-3 are elevated in CLE. Additionally, G3BP might be associated with the extent of skin lesions. There are no differences between G3BP and Gal-3 concentrations in SLE with and without LE-specific skin lesions.

Clinical characteristics of pruritus in patients with bullous pemphigoid: a preliminary questionnaire-based study.

INTRODUCTION: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Although pruritus is a leading symptom in BP, its specific characteristics have not been explored. AIM: To determine the itch characteristics in newly diagnosed BP patients by using the Questionnaire of Descriptive Assessment of Pruritus and visual analogue scale (VAS) and to correlate itch with disease severity. MATERIAL AND METHODS: The study included 32 patients with BP (mean age: 75.4 ±12.2 years; 20 women, 12 men), who filled in the questionnaire. Bullous Pemphigoid Disease Area Index (BPDAI) was assessed. RESULTS: In 78.1% of BP patients pruritus occurred at least once daily. Pruritus was most frequent in the evening and at night and frequently persisted for more than 10 min in more than a half of patients (long itch episodes). Aggravating factors were sweating (50.0%), heat (59.4%) and stress (46.9%), but the major relieving factor was cold (34.4%). Itch intensity in BP was assessed as moderate (mean VAS score: 5.8 points) and did not correlate with disease severity (BPDAI). BP patients declared difficulties caused by pruritus: falling asleep (53.1%) and awakening at night (50%). CONCLUSIONS: This study provided detailed characteristics in BP patients confirming that pruritus is classified as an important troublesome symptom. Therefore there is a need to search for therapeutic solutions.

The risk of small bowel adenocarcinoma in patients with Crohn's disease.

INTRODUCTION: Small bowel adenocarcinoma (SBA) is an unusual complication of Crohn's disease (CD). AIM: To describe the incidence rate, clinical features, and outcomes of SBA in a group of subsequent patients with CD. MATERIAL AND METHODS: We retrospectively analysed outpatient and hospital records and identified a group of patients with diagnosed CD. Then we reviewed all medical records of patients who reported for follow-up visits in a 14-year period. We identified a group of 103 patients, whose medical records were evaluated for the presence of SBA. RESULTS: Long-term follow-up carried out in the group of consecutively treated patients with CD revealed an 0.97% incidence rate of SBA. Cancer was located in the ileum and the clinical presentation was subileus and anaemia. The patient underwent ileocaecal resection, and the postoperative period was uneventful. CONCLUSIONS: SBA is a rare complication of CD. Although the authors are aware that the number of patients enrolled in the study is insufficient to draw far-reaching conclusions, the results obtained are significant for determination of the incidence rate of SBA in the Caucasian population of patients with CD. The key issue of effective treatment of patients with SBA was early detection of the lesion and R0 resection with proper lymphadenectomy. However, it is worth noting that in more advanced stages of SBA the future belongs to, and outcome improvement depends on, new regimes of adjuvant personalised chemotherapies. Further studies on the mechanisms of carcinogenesis in patients with CD are essential.

The association between neurological diseases, malignancies and cardiovascular comorbidities among patients with bullous pemphigoid: Case-control study in a specialized Polish center.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune bullous disease associated with higher mortality and coexisting comorbidities. The strongest relationship has been reported with neurological diseases (NDs) but the particular type of ND differed depending on the study. There are some doubts on the prevalence of other comorbidities. OBJECTIVES: The aim of this study was to compare the incidence of various comorbidities in a cohort of BP patients with controls. MATERIAL AND METHODS: A cohort of 218 patients (137 females, 81 males, aged 76.2 ±11.6 years) with newly diagnosed BP who were hospitalized at a specialized center in Poland in the years 2000-2014 was included in this retrospective study. The controls consisted of 168 sexand age-matched individuals. Univariate and multivariate logistic regression analyses were performed to assess the association between the groups studied. RESULTS: At least 1 ND was present in 33.5% of BP patients vs 11.3% of controls. A strong association between the incidence of NDs and BP was found (OR = 3.76; 95% CI = 2.13-6.65; p < 0.001), especially for dementia (20.6% vs 2.9%, OR = 7.89; 95% CI = 2.99-20.85; p < 0.001). Surprisingly, BP patients with ND were older than the BP patients without ND (79.2 vs 74.7 years), and similarly for dementia (81.08 vs 74.90 years). The same was observed in comparison with controls. Arterial hypertension, among other comorbidities, was a strong independent factor associated with BP (OR = 2.17; 95% CI = 1.35-3.49; p < 0.001). Malignancies were observed more frequently in BP patients than in controls (12.8% vs 9%) but such association was significant in univariate analysis only. CONCLUSIONS: Neurological diseases, particularly dementia, had a significant association with BP. A strong relationship with arterial hypertension and weak relationship with malignancies were noted. Thus, for appropriate medical care, patients with BP need accurate screening for dementia and control of comorbidities with interdisciplinary management.

Tetracycline, nicotinamide, and lesionally administered clobetasol as a therapeutic option to prednisone in patients with bullous pemphigoid: a comparative, retrospective analysis of 106 patients with long-term follow-up.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease associated with preexisting comorbidities and higher mortality. The interest in using therapy other than oral steroids in BP management results from severe complications and increased risk of death. The efficacy of oral doxycycline or whole-body application of topical clobetasol has been proven in randomized controlled trials. The case series study suggested that combination of tetracycline, nicotinamide, and lesionally administered clobetasol may also be useful. METHODS: We conducted a clinical 3-year retrospective study of treatment with tetracycline, nicotinamide, and lesionally administered clobetasol (TNC) in comparison to prednisone (P). Out of 106 patients (mean age 78 ± 9.9 years) with newly diagnosed BP, 59 received tetracycline 1.5 g/daily, nicotinamide 1.2 g/daily, and 0.05% lesionally administered clobetasol cream, and 47 patients - prednisone 0.5 mg/kg daily. RESULTS: The median time to disease control was achieved after 7 days in both groups. At 4 weeks, 93.2% of patients treated with TNC and 89.1% from P group achieved disease control. The median period between complete remission and relapse was 60 days in the TNC group and 90 days in the P group (P = 0.84). At least one relapse within 1 year was noted in 32.1% of patients from the TNC group and 50% from the P group (P = 0.09). The 1-year survival for the TNC and P groups was 83% and 65.9%, respectively (P = 0.04), and the 3-year survival was 71.2% and 48% (P = 0.019), respectively. CONCLUSIONS: Tetracycline and nicotinamide combined with lesionally administered clobetasol is an alternative, effective treatment with better survival rates compared to prednisone in BP.

Sex differences in outcomes of primary prevention implantable cardioverter-defibrillator therapy: combined registry data from eleven European countries.

Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials. Methods and results: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47-0.79; P = 0.0002). Conclusion: Our retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks.

Primary small bowel adenocarcinoma: current view on clinical features, risk and prognostic factors, treatment and outcome.

Small bowel adenocarcinoma (SBA) is a rare but increasing cause of gastrointestinal malignancy, being both a diagnostic and therapeutic challenge. The goal of treatment is margin negative resection of a lesion and local lymphadenectomy, followed by modern adjuvant chemotherapy combinations in selected cases. Improved outcomes in patients with SBA are encouraging, but elucidation of mechanisms of carcinogenesis and risk factors as well as improved treatment for this malignancy is very needed.

Giant gastrointestinal stromal tumour of rare sarcomatoid epithelioid subtype: case study and literature review.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract, but they represent less than 3% of all gastrointestinal tract malignancies. This is a detailed case study of a 52-year-old male patient treated for very uncommon histological subtype of gastric GIST with atypical clinical presentation, asymptomatic progress and late diagnosis. The resected tumour, giant in diameters, was confirmed to represent the most rare histopathologic subtype of GISTs - sarcomatoid epithelioid GIST. We report this case and review the literature with a special focus on pathomorphological evaluation, biological aggressiveness and prognostic factors. To our knowledge this is the first report of giant GIST of very uncommon sarcomatoid epithelioid subtype. It is concluded that clinicians should pay attention to the fact that initial diagnosis may be delayed due to mildly asymptomatic and non-specific clinical presentation. Asymptomatic tumours diagnosed at a late stage, which is often the case, can be large on presentation. Prognosis for patients diagnosed with GIST depend on tumour size, mitotic rate, histopathologic subtype and tumour location. That is why early diagnosis and R0 resection, which is usually feasible and safe even in giant gastric sarcomatoid epithelioid subtype of GISTs, are the key factors for further treatment and good prognosis.