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Despite the absence of a pattern of use or not of vitamin D in osteoporotic patients by health authorities, vitamin D remains widely prescribed by doctors. This dissonance can give rise to inappropriate prescriptions. This study made it possible to take stock of the prescription of vitamin D in patients taking anti-osteoporotic drugs in Occitanie, as well as to evaluate the prescription methods for cholecalciferol. [ABSTRACT FROM AUTHOR]

Male hypogonadism, which is characterized by low testosterone levels, has a significant impact on male sexual function, overall health, and fertility. Testosterone replacement therapy (TRT) is the conventional treatment for this condition, but it has potential adverse effects and is not suitable for men seeking to conceive. Testosterone plays an essential role in male sexual function, metabolism, mood, and overall well-being. Clomiphene citrate, a drug originally developed for female infertility, has recently gained attention as an off-label treatment for male hypogonadism. By blocking the negative feedback of estrogen on the hypothalamus and pituitary glands, clomiphene stimulates gonadotropin secretion, leading to increased endogenous testosterone production, which, in turn, improves sperm parameters and fertility and alleviates the symptoms of hypogonadism. Regarding the safety profile of clomiphene compared with TRT, clomiphene appears to confer a lower risk than TRT, which is associated with adverse effects such as polycythemia. Furthermore, combination therapy with clomiphene and anastrozole or human chorionic gonadotropin has been investigated as a potential approach to enhancing the effectiveness of treatments for improving hypogonadism symptoms. In conclusion, clomiphene citrate may offer a promising alternative to TRT for men with hypogonadism, particularly those desiring fertility preservations. However, its long-term efficacy and safety remain inadequately understood. Future research should focus on exploring the benefits of combination therapies and personalized treatment strategies based on individual patient characteristics. [ABSTRACT FROM AUTHOR]

Context Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). Objective To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. Design Open-label, phase 2 study. Participants Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16). Intervention Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). Main outcomes Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs). Results After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. Conclusion Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover. [ABSTRACT FROM AUTHOR]

Brain metastases represent a formidable challenge in cancer management, impacting a significant number of patients and contributing significantly to cancer-related mortality. Conventional diagnostic methods frequently fall short, underscoring the imperative for non-invasive alternatives. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), present promising avenues for exploration. These ncRNAs exert influence over the prognosis and treatment resistance of brain metastases, offering valuable insights into underlying mechanisms and potential therapeutic targets. Dysregulated ncRNAs have been identified in brain metastases originating from various primary cancers, unveiling opportunities for intervention and prevention. The analysis of ncRNA expression in bodily fluids, such as serum and cerebrospinal fluid, provides a noninvasive means to differentiate brain metastases from primary tumors. NcRNAs, particularly miRNAs, assume a pivotal role in orchestrating the immune response within the brain microenvironment. MiRNAs exhibit promise in diagnosing brain metastases, effectively distinguishing between normal and cancer cells, and pinpointing the tissue of origin for metastatic brain tumors. The manipulation of miRNAs holds substantial potential in cancer treatment, offering the prospect of reducing toxicity and enhancing efficacy. Given the limited treatment options and the formidable threat of brain metastases in cancer patients, non-coding RNAs, especially miRNAs, emerge as beacons of hope, serving as both diagnostic tools and therapeutic targets. Further clinical studies are imperative to validate the specificity and sensitivity of ncRNAs, potentially reshaping approaches to tackle this challenge and elevate treatment outcomes for affected patients.

Background. The significance of this study lies in the fact that short stature is highly prevalent among children, affec­ting 1–5 % of the population and having diverse causes. The child’s growth potential in the long term is largely depends on the effectiveness of the diagnostic system and the level of adherence to the prescribed therapy. The purpose was to improve the diagnosis of growth hormone deficiency (GHD) in children and adherence to recombinant human growth hormone (rhGH) therapy based on information about the regional prevalence of the disease and barriers to adherence. Materials and methods. A follow-up study was conducted from 2012 to 2020 at the Odesa Regional Children’s Hospital. The cohort included 94 children with GHD. The prevalence was determined by calculating the ratio of the number of all detected GHD cases to the children population per 100,000. Adherence was measured using the Morisky Medication Adherence Scale. The statistical processing of the results was done using t-test and chi-square methods, and p-values less than 0.05 were considered statistically significant. Results. An assessment of GHD prevalence, the level of adherence and the frequency of continuity of rhGH therapy in children in the Odesa region at the end of 2014 revealed the incompleteness of regional diagnosis of the disease (in Odesa, 1 : 11,200; in the Odesa region, 1 : 10,800), as well as a low level of acceptable adhe­rence (in 57.4 %) and insufficient frequency of continuity of therapy (in 76.9 %). These data formed the basis of the regional program for optimizing the identification and management of GHD in children, which included organizational, medical and social measures. By the end of 2020, the prevalence of GHD in Odesa was 1 : 4,300, and in the Odesa region, 1 : 5,100. The rate of acceptable adherence to rhGH therapy increased to 80.0 %, and frequency of continuity of therapy to 91.1 %. Conclusions. The regional program designed to improve the detection and management of GHD in children has been found to improve the diagnosis of the disease, increase adhe­rence to rhGH therapy, and the frequency of continuity of treatment. High adherence to treatment is a bioethical issue because it signifies a good partnership between physicians, children, and parents and indicates respect for patient autonomy.

Tobacco smoking has been highlighted as a major health challenge in modern societies. Despite not causing death directly, smoking has been associated with several health issues, such as cardiovascular diseases, respiratory disorders, and several cancer types. Moreover, exposure to nicotine during pregnancy has been associated with adverse neurological disorders in babies. Nicotine Replacement Therapy (NRT) is the most common strategy employed for smoking cessation, but despite its widespread use, NRT presents with low success and adherence rates. This is attributed partially to the rate of nicotine metabolism by cytochrome P450 2A6 (CYP2A6) in each individual. Nicotine addiction is correlated with the high rate of its metabolism, and thus, novel strategies need to be implemented in NRT protocols. Naturally derived products are a cost-efficient and rich source for potential inhibitors, with the main advantages being their abundance and ease of isolation. This systematic review aims to summarize the natural products that have been identified as CYP2A6 inhibitors, validated through in vitro and/or in vivo assays, and could be implemented as nicotine metabolism inhibitors. The scope is to present the different compounds and highlight their possible implementation in NRT strategies. Additionally, this information would provide valuable insight regarding CYP2A6 inhibitors, that can be utilized in drug development via the use of in silico methodologies and machine-learning models to identify new potential lead compounds for optimization and implementation in NRT regimes. [ABSTRACT FROM AUTHOR]

We have reviewed the literature for circular RNAs (circRNAs) with efficacy in preclinical pancreatic-cancer related in vivo models. The identified circRNAs target chemoresistance mechanisms (n=5), secreted proteins and transmembrane receptors (n=15), transcription factors (n=9), components of the signaling- (n=11), ubiquitination- (n=2), autophagy-system (n=2), and others (n=9). In addition to identifying targets for therapeutic intervention, circRNAs are potential new entities for treatment of pancreatic cancer. Upregulated circRNAs can be inhibited by antisense oligonucleotides (ASO), small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs) or clustered regularly interspaced short-palindromic repeats-CRISPR associated protein (CRISPR-CAS)-based intervention. The function of downregulated circRNAs can be reconstituted by replacement therapy using plasmids or virus-based vector systems. Target validation experiments and the development of improved delivery systems for corresponding agents were examined. [ABSTRACT FROM AUTHOR]

Plasminogen deficiency type 1 (PLGD-1, hypoplasminogenemia) is an ultra-rare, lifelong disease associated with development of fibrinous lesions in multiple organ systems. Depending on lesion location, clinical manifestations of PLGD-1 can result in acute and/or chronic respiratory airway disease which can compromise respiratory function leading to life-threatening events. Early recognition and effective treatment of airway obstruction caused by fibrinous lesions are critical to prevent morbidity due to respiratory compromise. However, physicians may not be familiar with the clinical presentation and management of PLGD-1, causing delays in diagnosis and treatment and potentially contributing to morbidity. Presented here is a case series of one adult and three pediatric patients with severe respiratory complications of PLGD-1 successfully managed by infusions of plasminogen, human-tvmh replacement therapy. Patients’ respiratory symptoms were resolved or greatly improved, and treatment was generally well tolerated. In all patients, baseline plasminogen activity was substantially increased with plasminogen replacement therapy administered initially every one to two days followed by extended interval dosing as symptoms were controlled or resolved. All four described cases support the clinical benefit of replacement therapy with plasminogen, human-tvmh in the resolution of life-threatening respiratory complications associated with PLGD-1. Clinical manifestations in addition to respiratory lesions were also improved or resolved with continued treatment.

This retrospective cohort study evaluates the safety and efficacy of replacement therapy with regard to pregnancy outcomes in hemophilia carriers. Hemophilia carriers face elevated bleeding risks during pregnancy, necessitating meticulous management, including replacement therapy with clotting factors. This research examines the records of 64 pregnant hemophilia carriers at King Fahad Medical City, Riyadh, from January 2010 to December 2023, analyzing their demographic details, hemophilia type and severity, replacement therapy specifics, and pregnancy outcomes. The study found that 62.5% of the participants had hemophilia A, with 43.8% categorized as severe. Most subjects (87.5%) received recombinant factor VIII at a median dosage of 30 IU/kg weekly. Adverse pregnancy outcomes included gestational hypertension (15.6%), preterm labor (18.8%), and postpartum hemorrhage (12.5%). The cesarean section rate was 28.1%. Neonatal outcomes were generally favorable, with median birth weights at 3100 g and mean Apgar scores of 8.2 and 9.1 at 1 and 5 min, respectively. Logistic regression analysis revealed no significant association between adverse events and therapy type or dosage, though a trend towards significance was noted with once-weekly administration (p = 0.082). The study concludes that replacement therapy is a viable method for managing hemophilia in pregnant carriers, leading to generally favorable maternal and neonatal outcomes. However, it underscores the importance of individualized treatment plans and close monitoring to effectively manage the risks associated with hemophilia during pregnancy. [ABSTRACT FROM AUTHOR]

For more than 50 years, immunoglobulin replacement therapy (IRT) has been a widely used and effective treatment for primary immunodeficiencies. It is also prescribed to patients who have certain autoimmune diseases like immune thrombocytopenia (ITP) and Guillain Barre syndrome. In these cases, immunoglobulin replacement therapy can help modify the course of the disease (immunomodulation). Although IRT therapy has been successful in treating ITP, it is costly and currently not covered by insurance for this condition. We report a clinical case of a boy with Evans-Fisher syndrome in whom genetic testing revealed carriage of several genetic variants with uncertain significance in genes associated with immune deficiency, legally allowing us to initiate regular reimbursed IRT therapy with a favorable response. Acknowledgments: This work was supported by a grant from the Medical University of Sofia (Council of Medical Science, project no. 7346/2021), grant no. 171/2022 and Sobi Grant 202. [ABSTRACT FROM AUTHOR]

Hypothyroidism is one of the common endocrine diseases. Its established treatment involves only various forms of levothyroxine (T4). Regardless of achieving normal levels of thyroid hormones with optimal doses of levothyroxine, a significant proportion of patients continue to have unexplained complaints and report a reduced quality of life. Attempts to find an individualized formula for the treatment of hypothyroidism, including a small dose of triiodothyronine (T3 ), have been ongoing for many decades. Interest in combined T4 /T3 treatment experiences high and low tides of scientific and practical interest. This review focuses on some aspects of levothyroxine treatment and on the alternative views offered in recent years about the place of combined T4 /T3 therapy in a very small proportion of patients. The opinions of the leading experts in Europe were used as a basis. Practical approaches to switching to such treatment are outlined. Attention has been drawn to the fact that informed consent from the patient is necessary for the application of such non-traditional schemes. Isolated treatment with T3 or dried extracts is strictly not recommended. In conclusion, adherence to the guidelines for good clinical practice established in the country and the algorithms of the NHF guarantees sustainable results and a legal basis for the replacement treatment in hypothyroidism. [ABSTRACT FROM AUTHOR]

Hemophilia is an inherited bleeding disorder caused by malfunctioning or lacking blood coagulation factor VIII (hemophilia A) or IX (hemophilia B). Currently, the main treatments for these X-linked diseases are replacement therapy using periodic and regular injections of plasma-derived coagulation factors or their recombinant products. The use of recombinant coagulation factors is due to the need for periodic and regular injections to prevent bleeding in the acute type of hemophilia and in turn imposing a financial burden on patients. On the other hand, this treatment method is not available to all patients, especially those in developing countries. Recently, gene therapy has been proposed as a suitable, cost-effective, and permanent treatment option for hemophilia. This method is expected to solve the problems we currently face in treating hemophilia. Hemophilia is suitable for gene therapy since an abnormal gene is responsible for the disease. During the last two years, successful clinical trials for gene therapy using vectors derived from adeno-associated virus for both hemophilia A and hemophilia B have been conducted and approved for administration. Moreover, new methods based on gene-cell therapy and genome editing are under investigation for the treatment of hemophilia. This review article deals with different approaches for hemophilia treatments from the past to the present, particularly gene therapy methods.

Male hypogonadism, which is characterized by low testosterone levels, has a significant impact on male sexual function, overall health, and fertility. Testosterone replacement therapy (TRT) is the conventional treatment for this condition, but it has potential adverse effects and is not suitable for men seeking to conceive. Testosterone plays an essential role in male sexual function, metabolism, mood, and overall well-being. Clomiphene citrate, a drug originally developed for female infertility, has recently gained attention as an off-label treatment for male hypogonadism. By blocking the negative feedback of estrogen on the hypothalamus and pituitary glands, clomiphene stimulates gonadotropin secretion, leading to increased endogenous testosterone production, which, in turn, improves sperm parameters and fertility and alleviates the symptoms of hypogonadism. Regarding the safety profile of clomiphene compared with TRT, clomiphene appears to confer a lower risk than TRT, which is associated with adverse effects such as polycythemia. Furthermore, combination therapy with clomiphene and anastrozole or human chorionic gonadotropin has been investigated as a potential approach to enhancing the effectiveness of treatments for improving hypogonadism symptoms. In conclusion, clomiphene citrate may offer a promising alternative to TRT for men with hypogonadism, particularly those desiring fertility preservations. However, its long-term efficacy and safety remain inadequately understood. Future research should focus on exploring the benefits of combination therapies and personalized treatment strategies based on individual patient characteristics.

Factor XIII deficiency is an extremely rare autosomal recessive genetic disorder, occurring in 1 of 3–5 million people, and is associated with perinatal complications, such as habitual abortion and prolonged bleeding. Although plasma‐derived factor XIII (Fibrogamin®) carries a risk of infection and contains very low concentrated forms of factor XIII (FXIII) used for a pregnant woman with congenital coagulation factor XIII deficiency, recombinant factor XIII (rFXIII, Novo Thirteen®; Tretten®, Novo Nordisk, Bagsværd, Denmark), which has no risk of infection and is highly concentrated, has emerged as a novel formulation. Herein, we report the first case of a Japanese pregnant woman with congenital coagulation factor XIII deficiency successfully managed by rFXIII. She had a good perinatal course without pregnancy‐related complications and transfusion through the perinatal period. [ABSTRACT FROM AUTHOR]

Hereditary factor X deficiency (HFXD) is a rare genetic bleeding disorder, affecting approximately 1 in 1,000,000 individuals globally, and resulting in abnormally low activity of clotting factor X (FX). Diagnosis may occur early in life, particularly in patients with a family history of the disorder or severe deficiency, or later in life for those with mild-moderate deficiency. Regardless of age at diagnosis, this disorder can significantly impact the lives of patients, as well as those of caregivers and/or family members. Alongside a wide historical array of HFXD treatments, including supportive care with blood transfusions, FX replacement with fresh frozen plasma or prothrombin complex concentrates, specific replacement has been made possible with the isolation and concentration of human plasma-derived FX for therapeutic use, offering the potential for a streamlined prophylactic regimen and improved quality of life and wellbeing. Two recent case studies describe the diagnosis and management of children with HFXD in India and the Philippines, both of whom were diagnosed in infancy following severe bleeding episodes. They share important similarities but highlight key differences in the experience of diagnosis and management of HFXD. Together they illustrate the lack of a specific target population subgroup for this rare but serious bleeding disorders, and the importance of checking FX levels (among other clotting factors) when prothrombin time (PT) and partial thromboplastin time (PTT) are prolonged.

Tobacco smoking has been highlighted as a major health challenge in modern societies. Despite not causing death directly, smoking has been associated with several health issues, such as cardiovascular diseases, respiratory disorders, and several cancer types. Moreover, exposure to nicotine during pregnancy has been associated with adverse neurological disorders in babies. Nicotine Replacement Therapy (NRT) is the most common strategy employed for smoking cessation, but despite its widespread use, NRT presents with low success and adherence rates. This is attributed partially to the rate of nicotine metabolism by cytochrome P450 2A6 (CYP2A6) in each individual. Nicotine addiction is correlated with the high rate of its metabolism, and thus, novel strategies need to be implemented in NRT protocols. Naturally derived products are a cost-efficient and rich source for potential inhibitors, with the main advantages being their abundance and ease of isolation. This systematic review aims to summarize the natural products that have been identified as CYP2A6 inhibitors, validated through in vitro and/or in vivo assays, and could be implemented as nicotine metabolism inhibitors. The scope is to present the different compounds and highlight their possible implementation in NRT strategies. Additionally, this information would provide valuable insight regarding CYP2A6 inhibitors, that can be utilized in drug development via the use of in silico methodologies and machine-learning models to identify new potential lead compounds for optimization and implementation in NRT regimes.

Background. Patients with hemophilia are protected from thrombosis by a deficiency of one of coagulation factors, therefore thrombotic complications are rare in them. Currently, few descriptions of spontaneous venous thrombosis in adult hemophiliacs can be found in the literature. Even fewer data of thromboembolic complications are reported in pediatric practice. At present, no clear recommendations are given for the management of thrombotic complications in children with hemophilia, which requires further study of this issue to develop prevention and treatment regimens, including otogenic sinus thrombosis in this category of patients.Case description. A 7-year-old boy was transferred from the Somatic Hospital to the Intensive Care Unit of Regional Clinical Hospital No. 2 in Tyumen (Russia) with an Otorhinolaryngology Unit. He was diagnosed with non-perforative form of acute right-sided suppurative otitis media, acute right-sided mastoiditis, thrombosis of the right sigmoid sinus. The anamnesis shows that the child is diagnosed with hemophilia A, of moderate severity (factor VIII level — 5%), for which he has been receiving factor VIII replacement therapy for the last year. Upon admission, a general blood test revealed no abnormalities, with a slight increase in acute-phase parameters: C-reactive protein, fibrinogen, signs of hypocoagulation. Due to negative dynamics, the child underwent anthromastoidotomy against the background of intensive replacement therapy. Surgery revealed the presence of granulation tissue with hemorrhagic thrombi in the antrum and aditus. In the postoperative period, replacement therapy was accompanied with antibacterial and anticoagulant therapy.Conclusion. The management of patients with otogenic sinus thrombosis against the background of hereditary factor VIII deficiency is a difficult task. On the one hand, it requires surgical intervention and anticoagulant therapy in order to prevent further thrombosis, on the other hand — intensive replacement therapy in order to reduce the risks of hemorrhagic complications. The described case demonstrates the need for an interdisciplinary approach to the diagnosis and treatment of a patient with otogenic thrombosis of lateral sinus against the background of hemophilia A. The approach is to minimize the risks of intraoperative complications and insure a favorable outcome.

Aim: An open‐label phase 2/3 study of plasminogen, human‐tvmh administered intravenously in paediatric and adult subjects with type 1 plasminogen deficiency was conducted. Interim data was previously reported. The final data on 15 subjects who completed the study up to a maximum of 124 weeks are reported here. Methods: The primary objectives were to evaluate efficacy of plasminogen replacement therapy on clinically evident or visible lesions during 48 weeks of dosing and to achieve an increase in trough plasminogen activity levels by at least an absolute 10% above baseline during 12 weeks of treatment. Results: The primary efficacy endpoint was achieved, as 100% of subjects (n = 11) with visible and assessable non‐visible lesions at baseline demonstrated ≥ 50% improvement after 48 weeks of study drug treatment with plasminogen, human‐tvmh. All subjects achieved the targeted ≥ 10% increase in trough plasminogen activity above baseline through Week 12. Plasminogen, human‐tvmh at a dose of 6.6 mg/kg administered every 2–5 days for 48 weeks and every 1–7 days for up to 124 weeks was well tolerated. Conclusion: This study provides additional evidence regarding the long‐term safety and clinical utility of replacement therapy with human plasminogen for the treatment of children and adults with type 1 plasminogen deficiency. Plasminogen, human‐tvmh received marketing approval on June 4, 2021. This trial was registered at www.clinicaltrials.gov as #NCT02690714. [ABSTRACT FROM AUTHOR]

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This retrospective cohort study evaluates the safety and efficacy of replacement therapy with regard to pregnancy outcomes in hemophilia carriers. Hemophilia carriers face elevated bleeding risks during pregnancy, necessitating meticulous management, including replacement therapy with clotting factors. This research examines the records of 64 pregnant hemophilia carriers at King Fahad Medical City, Riyadh, from January 2010 to December 2023, analyzing their demographic details, hemophilia type and severity, replacement therapy specifics, and pregnancy outcomes. The study found that 62.5% of the participants had hemophilia A, with 43.8% categorized as severe. Most subjects (87.5%) received recombinant factor VIII at a median dosage of 30 IU/kg weekly. Adverse pregnancy outcomes included gestational hypertension (15.6%), preterm labor (18.8%), and postpartum hemorrhage (12.5%). The cesarean section rate was 28.1%. Neonatal outcomes were generally favorable, with median birth weights at 3100 g and mean Apgar scores of 8.2 and 9.1 at 1 and 5 min, respectively. Logistic regression analysis revealed no significant association between adverse events and therapy type or dosage, though a trend towards significance was noted with once-weekly administration (p = 0.082). The study concludes that replacement therapy is a viable method for managing hemophilia in pregnant carriers, leading to generally favorable maternal and neonatal outcomes. However, it underscores the importance of individualized treatment plans and close monitoring to effectively manage the risks associated with hemophilia during pregnancy.

Hyperkalemia, metabolic acidosis, and acute uremia are the main symptoms in patients with severe acute renal failure (SARF). Its clinical symptoms are obvious, and it is extremely harmful. It needs to take active and effective measures for treatment. CRRT refers to any extracorporeal blood purification treatment technique designed to replace impaired renal function for 24 h or nearly 24 h. Hemodialysis treatment is a treatment process in which the patient's blood is discharged from the body, passes through the dialysis membrane and dialysis machine, removes excess toxins and water in the body, corrects electrolyte and acid-base disorders, and then returns the blood to the body. In order to explore the efficacy of replacement therapy and hemodialysis in the treatment of severe acute renal failure, the data samples were randomly divided into observation group and control group, who were given conventional treatment, hemodialysis and replacement therapy, respectively. Clinical data show that after replacement therapy and hemodialysis in patients with severe acute renal failure in the observation group, the levels of parathyroid hormone, renin, and quality of life were all improved, with an improvement rate of 9.47%, which has certain promotional value. [ABSTRACT FROM AUTHOR]

Summary: Objective: To investigate the feasibility and clinical efficacy of laparoscopic ureteroplasty with oral mucosal graft for ureteral stricture and describe the initial experience of eighteen operations. Methods: A retrospective analysis was performed on the clinical data of 18 patients who underwent laparoscopic ureteroplasty with oral mucosal graft for long segment or complex ureteral stricture admitted to the Second Affiliated Hospital of Anhui Medical University from July 2018 to June 2021. After the stricture ureter segment was freed during the operation, the ureteral stenosis segment was longitudinally cut. The required oral mucosa is removed according to the length of the stenosis. Oral mucosal grafts were harvested and placed in the ureter as an anterior onlay with omental wrapping. Results: Ureteral repair was performed laparoscopically in all cases, with no conversion to open surgery and no serious complications. The median length of ureteral stenosis was 3 cm (range, 2–7 cm), the mean operative time was 205.8 ± 33.4 min, indwelling time of the drainage tube was 4.9 ± 1.6 days, and the median length of postoperative stay was 7 days (range, 4–14 days). The double J tube was removed three to six weeks postoperatively. One of the eighteen patients had restenosis after surgery, and the other patients showed no deterioration of the severity of the obstructive uropathy after follow-up imaging examination. Conclusion: Laparosopic ureteroplasty with oral mucosal graft is a simple, safe and efficient option for the treatment of ureteral stricture. Although the results of the initial experience are encouraging, a large cohort study with longer follow-up period is need to be done.

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency. One hundred and sixteen CLL patients were recruited, 63% were males, and the median age was 68 years; 44% had bronchiectasis and 76% never smoked. Forty-nine patients received IVIG and 88 SCIG, including 28 patients who shifted from IVIG to SCIG. Despite similar baseline IgG levels, patients receiving SCIG achieved higher IgG after at least +6 months (p = 0.0009). We observed that SCIG can decrease the cumulative incidence of first (HR 0.39 p < 0.0001) and second (HR 0.56 p = 0.0411) infection more than IVIG. The effect was remarkable in that patients were able to reach at least 6 g/L of IgG after 6 months of treatments (p < 0.0001). Replacement therapies were well tolerated with less adverse events and a lower discontinuation rate in patients was managed with SCIG than IVIG. In this study we describe the clinical features of a large cohort of CLL with secondary antibody deficiency receiving IG. We demonstrated that SCIG are active and well tolerated drugs that allows to reach higher IgG levels and decrease the rate of infections better than IVIG, in particular when IgG levels reach 6 g/L.

Hypogonadism is a condition associated with a decrease in the functional activity of the testicles, accompanied by a decrease in the level of androgens and (or) a violation of the process of spermatogenesis. It is known that androgens and their main representative, testosterone, are of fundamental importance for the development and maintenance of the reproductive and sexual functions of the male reproductive system. At the same time, low testosterone levels are associated with both reproductive and metabolic disorders, including phosphorus-calcium, fat, carbohydrate, and protein metabolism. In addition, to date, data have been accumulated on the correlation of hypogonadism with cardiovascular diseases, which once again emphasizes the problem of testosterone deficiency, especially for patients of the middle and older age groups. However, carrying out testosterone replacement therapy always requires a strict and competent choice of a «target audience» among patients from a specialist. Today, on the pharmaceutical market, there is a wide arsenal of testosterone-containing drugs in various forms for use, which have an unequal «efficacy-safety» profile. In this review, we have analyzed modern approaches to the diagnosis and treatment of hypogonadism, the selection of a target group of patients to obtain the most effective and safe treatment outcome and described testosterone preparations and their dosage forms with potential advantages and disadvantages. Thus, the information presented in the article is aimed at optimizing the management of men with hypogonadism.

Endometriosis is a chronic inflammatory estrogen-dependent disease characterized by the growth of endometrial-like tissue outside the physiological region. Despite the fact that this disease is common, laparoscopic surgery is currently the gold standard in the treatment of endometriosis. In this regard, it is necessary to develop new effective methods of minimally invasive therapy for endometriosis. One of the promising areas in the treatment of endometriosis is cell therapy. Cellular therapy is a vast branch of therapeutic methods with various agents. Potential cell therapies for endometriosis may be based on the principle of targeting aspects of the pathogenesis of the disease: suppression of estrogen receptor activity, angiogenesis, fibrosis, and a decrease in the content of stem cells in endometriosis foci. In addition, immune cells such as NK cells and macrophages may be promising agents for cell therapy of endometriosis. Standing apart in the methods of cell therapy is the replacement therapy of endometriosis. Thus, many studies in the field of the pathogenesis of endometriosis can shed light not only on the causes of the disease and may contribute to the development of new methods for personalized cell therapy of endometriosis. [ABSTRACT FROM AUTHOR]

The fact that growth hormone (GH) plays an important role in health after the cessation of growth requiring replacement therapy in adult life has only been recognised in the last three decades. This has only been made possible by recombinant technology providing GH supplies required to undertake investigations in the physiology of GH action and the benefits of replacement therapy in patients identified by rigorously validated diagnostic tests for GH deficiency (GHD). Human studies have revealed important regulatory roles in substrate metabolism, sodium homeostasis, body composition, and physical function. GH-induced anabolism is achieved by stimulating amino acid incorporation into protein while reducing oxidative loss simultaneously enhancing lipid utilisation by stimulating fatty acid oxidation and reducing lipid storage. Sodium and fluid retention are enhanced by activating the renin–angiotensin system and distal renal tubular reabsorption. GH stimulates the aerobic and anaerobic energy systems that underpin muscle and cardiovascular function. These pleiotropic actions explain the clinical picture of increased adiposity, reduced lean mass, and impaired physical and psychological function in the GHD adult, all of which are reversed when GH is replaced. Women require a greater replacement dose of GH than men. This is because androgens enhance while oestrogens attenuate GH action. The oestrogen effect is route-dependent, occurring with oral delivery blunting the liver-mediated actions of GH by directly inhibiting GH receptor signalling, global experience spanning over 30 years has attested to the safety, efficacy, and benefits of replacement therapy for adults with GHD. [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) is a common complication of severe burn injuries and contributes to morbidity and mortality. It is exacerbated in burn patients by elevated serum creatinine and pro-inflammatory cytokines, leading to immune dysregulation. Chronic renal replacement therapy is standard of care and removes cytokines to return the body to homeostasis. Continuous veno-venous hemodiafiltration (CVVHDF) is a high-filtration method to enhance cytokine clearance; we analyze a step-down approach for improved outcomes in burn patients. Methods: This study reviewed 15 burn patients at Akron Children's Hospital stratified into 2 groups: high-flow CVVHDF with step-down approach versus standard CVVHDF. A normocarbia bicarbonate-based dialysate solution and citrate anticoagulation was applied, and blood flow rate was maintained greater than 200 mL/min. Results: Fifteen burn patients at Akron Children's Hospital were separated into groups managed with high-flow CVVHDF (n = 9) and standard-flow CVVHDF (n = 6). All 15 developed AKI symptoms and diuretic-resistant fluid overload, with 4/15 displaying fluid overload greater than 40%. The most common indication for hemofiltration was acute tubular necrosis (11/15). Average time on CVVHDF was 20.2 days and length of admission was 58.6 days. Vasodepressor dependency index was significantly reduced in the high-flow group at 48 h, but no significant difference in mortality was identified. No significant difference was identified in adverse reactions, notably electrolyte imbalances. Conclusion: The literature on the efficacy of high-flow CVVHDF is limited. This study suggests improved mortality rates and length of stay with high flow compared to the literature. Further studies with multicenter involvement are necessary. [ABSTRACT FROM AUTHOR]

Therapy for hemophilia B is aimed at replacing the congenital deficiency of coagulation factor IX (FIX). For replacement therapy, several FIX concentrates derived from donated human plasma or engineered by recombinant DNA technology are currently commercially available. The use of these products is well established and permit patients a relatively normal life. To further improve treatment efficacy, recombinant FIX products with a prolonged half-life have been developed, allowing relaxed prophylactic dosing and reducing treatment burden. In this review, we explore the current FIX replacement options for hemophilia B patients by analyzing the outcomes of their main clinical trials. We cover advances in the FIX molecules with extended half-life (EHL). Published literature on products for replacement of hemophilia B was retrieved using PubMed with no temporal limits. The recent introduction of recombinant EHL FIX products has represented a major advance in the therapeutic management of hemophilia B patients, permitting both a reduction of treatment burden and improving patients' compliance to prophylaxis and, ultimately, quality of life. [ABSTRACT FROM AUTHOR]

Patients with adrenal insufficiency (AI) are treated with conventional or modifiedrelease glucocorticoid (GC) replacement therapy (GRT). Although current GRT regimens aim to mimic the physiological circadian pattern of cortisol secretion, temporary phases of hypo- and hypercortisolism are common. There is good evidence that prolonged phases of hypo- or hypercortisolism are associated with impaired cognitive functioning. However, little is known about cognitive functioning in patients with AI regarding the effects of dosage and duration of glucocorticoid replacement therapy. There is also little data available comparing the effects of GC therapy on patients with primary and secondary forms of AI as well as with respect to different formulas. This Mini-Review gives an overview of the current studies on GRT for primary and secondary AI and their impact on cognition. Strengths and weaknesses of the studies and their Implications for clinical daily routine are discussed with a special emphasis on practical considerations for the treating endocrinologist. [ABSTRACT FROM AUTHOR]

Abstract Ichthyosis covers a wide spectrum of diseases affecting the cornification of the skin. In recent years, new advances in understanding the pathophysiology of ichthyosis have been made. This knowledge, combined with constant development of pathogenesis-based therapies, such as protein replacement therapy and gene therapy, are rather promising for patients with inherited skin diseases. Several ongoing trials are investigating the potency of these new approaches and various studies have already been published. Furthermore, a lot of case series report that biological therapeutics are effective treatment options, mainly for Netherton syndrome and autosomal recessive congenital ichthyosis. It is expected that some of these new therapies will prove their efficacy and will be incorporated in the treatment of ichthyosis.

This paper summarized the perioperative nursing experience of a child with hemophilia B and adenoid hypertrophy undergoing surgery. The treatment and nursing plan was formed based on the multidisciplinary consultation and discussion. Health education about usage and precautions of prothrombin complex concentrate in replacement therapy was carried out before treatment. Based on the theory of enhance recovery after surgery, a comprehensive perioperative nursing interventions were carried out, including diet care, pain management, body temperature management, preoperative adaptive training. An effort was also made to enhance the psychological care, pre-discharge readiness assessment, discharge planning and guidance and continuous care after discharge. (本文总结1例血友病B患儿腺样体肥大围手术期的护理经验。经多学科会诊讨论并制定治疗护理方案, 告知替代治疗中凝血酶原复合物的使用方法及注意事项, 实施基于加速康复外科理念的围术期护理(饮食护理、疼痛管理、体温管理、术前适应性锻炼), 加强心理干预、出院前的出院准备度评估、出院计划与指导、出院后延续护理等。)

Patients with adrenal insufficiency (AI) are treated with conventional or modified-release glucocorticoid (GC) replacement therapy (GRT). Although current GRT regimens aim to mimic the physiological circadian pattern of cortisol secretion, temporary phases of hypo- and hypercortisolism are common. There is good evidence that prolonged phases of hypo- or hypercortisolism are associated with impaired cognitive functioning. However, little is known about cognitive functioning in patients with AI regarding the effects of dosage and duration of glucocorticoid replacement therapy. There is also little data available comparing the effects of GC therapy on patients with primary and secondary forms of AI as well as with respect to different formulas. This Mini-Review gives an overview of the current studies on GRT for primary and secondary AI and their impact on cognition. Strengths and weaknesses of the studies and their Implications for clinical daily routine are discussed with a special emphasis on practical considerations for the treating endocrinologist.

Summary: Congenital factor VII (FVII) deficiency is a rare bleeding disorder characterised by a wide molecular and clinical heterogeneity. We investigated the clinical phenotype of 193 patients and F7 genotype of 55/193 patients with FVII deficiency throughout China and showed their current status of management. The most frequent bleeding symptoms were epistaxis (44.6%), cutaneous (38.9%), oral cavity (40.4%) bleeding and menorrhagia (44.3% of females of reproductive age). Fatal central nervous system bleeding and disabling joint bleeding occurred in three patients each. The majority of patients (89.6%) had FVII activity (FVII:C) ≤10% and the proportion of symptomatic patients in this group (79.8%) was significantly higher than that in the groups with FVII:C >10%–25% (41.7%) and >25%–50% (37.5%) (χ2 = 13.641, p = 0.001). Major bleeds occurred only in patients with FVII:C ≤10%. In total 55 patients underwent genotype analysis: most variants were missense (62.5%) and most patients had homozygous/compound heterozygous (85.4%) variants. Prothrombin complex concentrates (72.4%) were the most frequently used on‐demand replacement therapy. Prophylaxis before delivery decreased the risk of postpartum bleeding in women (χ2 = 69.243, p = 0.000). Our study provides useful information on the phenotype, genotype and current status of FVII‐deficiency patients management and may promote further exploration and care of this population in the future. [ABSTRACT FROM AUTHOR]

To investigate the feasibility and clinical efficacy of laparoscopic ureteroplasty with oral mucosal graft for ureteral stricture and describe the initial experience of eighteen operations. A retrospective analysis was performed on the clinical data of 18 patients who underwent laparoscopic ureteroplasty with oral mucosal graft for long segment or complex ureteral stricture admitted to the Second Affiliated Hospital of Anhui Medical University from July 2018 to June 2021. After the stricture ureter segment was freed during the operation, the ureteral stenosis segment was longitudinally cut. The required oral mucosa is removed according to the length of the stenosis. Oral mucosal grafts were harvested and placed in the ureter as an anterior onlay with omental wrapping. Ureteral repair was performed laparoscopically in all cases, with no conversion to open surgery and no serious complications. The median length of ureteral stenosis was 3 cm (range, 2–7 cm), the mean operative time was 205.8 ± 33.4 min, indwelling time of the drainage tube was 4.9 ± 1.6 days, and the median length of postoperative stay was 7 days (range, 4–14 days). The double J tube was removed three to six weeks postoperatively. One of the eighteen patients had restenosis after surgery, and the other patients showed no deterioration of the severity of the obstructive uropathy after follow-up imaging examination. Laparosopic ureteroplasty with oral mucosal graft is a simple, safe and efficient option for the treatment of ureteral stricture. Although the results of the initial experience are encouraging, a large cohort study with longer follow-up period is need to be done. • Laparoscopic ureteroplasty with oral mucosa graft is suitable for long-segment and multi-segment ureteral stricture. • Laparoscopic ureteroplasty with oral mucosa graft has the advantages of good effect, less trauma and quick recovery • Oral mucosa is more likely to survive after repair and has a lower probability of contracture and postoperative restenosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Although craniopharyngiomas are pathologically defined as benign tumors, their lesions could involve the hypothalamic–pituitary axis and adjacent to several important anatomical structures. Treatment strategies, including surgery and radiation, have a higher risk of damaging these important structures, which leads to excess recurrence and disability rates. Endocrine deficiencies caused by hypothalamic–pituitary axis damage are the most common symptoms and postoperative complications of craniopharyngioma patients, which severely affect perioperative and long-term treatment effects. However, limited studies have focused on the endocrine deficiencies of craniopharyngioma patients. In this study, the influencing factors and replacement therapies for pre- and postoperative pituitary hormone deficiency were retrospectively analyzed in 126 craniopharyngioma patients, which provides evidence for surgical strategy selection and long-term management during craniopharyngioma treatments. Background: Pituitary hormone deficiency (PHD) is one of the most common symptoms and postoperative complications of craniopharyngiomas (CPs). However, the risk factors for PHD in CPs are little known. The purpose of this study was to analyze the risk factors of pre- and postoperative PHD and to investigate replacement therapy for CP patients. Methods: A retrospective study of 126 patients diagnosed with CP was performed. Univariate analysis was performed using Pearson's chi-squared test or Fisher's exact test, and a multiple logistic binary regression model was used to identify the influencing factors of pre- and postoperative PHD in craniopharyngioma. Results: Children and patients with hypothalamic involvement were more likely to have preoperative PHD. Patients with suprasellar lesions had a high risk of postoperative PHD, and preoperative PHD was a risk factor for postoperative PHD. Conclusion: Children have a high incidence of preoperative PHD. Preoperative PHD can serve as an independent risk factor for postoperative PHD. Preoperative panhypopituitarism can serve as an indication of pituitary stalk sacrifice during surgery. The management of replacement therapy for long-term postoperative endocrine hormone deficiency in patients with craniopharyngioma should be enhanced. [ABSTRACT FROM AUTHOR]

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency. One hundred and sixteen CLL patients were recruited, 63% were males, and the median age was 68 years; 44% had bronchiectasis and 76% never smoked. Forty-nine patients received IVIG and 88 SCIG, including 28 patients who shifted from IVIG to SCIG. Despite similar baseline IgG levels, patients receiving SCIG achieved higher IgG after at least +6 months (p = 0.0009). We observed that SCIG can decrease the cumulative incidence of first (HR 0.39 p < 0.0001) and second (HR 0.56 p = 0.0411) infection more than IVIG. The effect was remarkable in that patients were able to reach at least 6 g/L of IgG after 6 months of treatments (p < 0.0001). Replacement therapies were well tolerated with less adverse events and a lower discontinuation rate in patients was managed with SCIG than IVIG. In this study we describe the clinical features of a large cohort of CLL with secondary antibody deficiency receiving IG. We demonstrated that SCIG are active and well tolerated drugs that allows to reach higher IgG levels and decrease the rate of infections better than IVIG, in particular when IgG levels reach 6 g/L. [ABSTRACT FROM AUTHOR]

Objective: To understand differences in thyroid hormone replacement therapy with levo‐thyroxine (l‐T4) between acquired and congenital hypothyroid (CH) patients. Design: We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy. Patients and Measurements: A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18−58). Serum TSH, FT3, FT4, l‐T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups. Results: The daily weight‐based l‐T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p =.03). FT3/FT4 ratio was significantly higher in the EU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in the TP group, but not in the EU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects. Conclusions: Adult CH patients require a higher daily l‐T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic−pituitary−thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH. [ABSTRACT FROM AUTHOR]

To compare healthcare costs in patients with non-inhibitor hemophilia A treated with Rurioctocog Alfa Pegol (FVIII-PEG) versus Antihemophilic Factor (Recombinant), FC Fusion Protein (rFVIIIFc). Administrative claims data from the Merative MarketScan Commercial (Commerical) and Medicaid (Medicaid) databases were used for these analyses. Males with non-inhibitor hemophilia A treated with FVIII-PEG or rFVIIIFc from 1 January 2016 to 31 March 2021 were identified (earliest treatment = index). Patients were required to have continuous database enrollment for six months before and after the index date. Follow-up was variable in length until disenrollment or study end. All-cause and hemophilia-related healthcare costs were reported per-patient per month [PPPM] and the average weekly dose during follow-up was compared between treatment groups. Generalized linear regressions were used to estimate multivariable-adjusted differences in total costs and weekly dosage in the two treatment groups. A total of 131 FVIII-PEG (66 Commercial; 65 Medicaid) and 204 rFVIIIFc (111 Commercial; 93 Medicaid) patients were eligible. Mean age was 20.5 and 24.4 for FVIII-PEG and rFVIIIFc in Commercial and 14.9 and 17.5 for FVIII-PEG and rFVIIIFc in Medicaid. PPPM mean (standard deviations [SD]) total healthcare costs in Commercially insured patients were $35,868 [$21,717] for FVIII-PEG vs $40,424 [$25,882] for rFVIIIFc. Costs in Medicaid were $27,495 [$23,243] for FVIII-PEG vs $30,237 [$28,430] for rFVIIIFc. After adjusting for baseline characteristics, the costs for rFVIIIFc (vs FVIII-PEG) were higher by $5,215 in Commercial and $3,895 in Medicaid, but the differences were not statistically significant (p > 0.05). Similar findings were observed for hemophilia-specific healthcare costs. The adjusted mean weekly dose was 6,047 vs 4,892 IU, p = 0.21 for FVIII-PEG vs rFVIIIFc in Commercial and 5,549 vs 7,228 IU, p = 0.07 for FVIII-PEG vs rFVIIIFc in Medicaid. Healthcare costs and treatment dosing were similar (p > 0.05) for non-inhibitor hemophilia A patients treated with FVIII-PEG and rFVIIIFc. [ABSTRACT FROM AUTHOR]

Aim of the research was to study and analyze the features of opioids and narcotics using by drug addicted people and the role of replacement drugs in treatment and recovery of the patient. Materials and methods: We conducted a systematic review and meta-analysis of studies. Were used Systematic literature reviews and meta-analyses. The material of the article was data from the scientific literature, processed and analyzed by generalization and systematization. The scientific research ensues the fundamentals of assessment development of significant reviews. The ensuing databases were used: (for searching considerable literature to study and analyze the features of opioids and narcotics using by drug addiction people and the role of replacement drugs in treatment and recovery of the patient) Pub Med, Web of Science, Clinical key, Tomson Routers, Google Scholar, Cochrane Library, and Elsevier bases. Additionally studied national and internationals policy and guidelines and also grey literature. Results: Addiction is well known to be associated with its high level of physical and mental disorders. Most chronic chemical dependencies of drug addiction are also associated with its very high mortality rates, estimated to be several times those of the non-clinical population. Since addictive substances are known to disrupt cell growth and cell division, it can be assumed, that they particularly affect dividing cells, such as stem cell pools and progenitor cells. It is also known, that they either individually or in combination potentiate apoptosis, i.e., contribute to this effect. The medicine of aging in recent times has become an independent scientific discipline. The cellular aging hypothesis suggests the aging phenotype. The organism is associated with cellular correlates of age associated changes including cell loss, reduced cell velocity, renewal and more aging, negligible functional and non-replicating cells in tissues. So, the anti-growth effects of drug addiction can reasonably occur throughout the body. Expect signs of accelerated aging to be evident. One would expect such a putative progeroid effect to occur subject to increased morbidity and mortality rates, clinically observed almost identically in drug addicts as is the case in the geriatric population. In this connection there are various changes, consideration of all clinical aspects' expression of this general toxicology hypothesis of opioids is needed. Conclusion: Pharmacological management of drug use should be only one component of treatment for drug needs, tailored to a comprehensive needs assessment of the child or young person, carried out in conjunction with appropriate psychological therapy and mental health interventions, and in the context of a clear and applied approach to the clinical management system. Caution is required when leaving these establishments due to the risk of overdose and in the transition to adult services. Physicians should carefully consider the degree of dependence on any substance, especially when alcohol and other substances, such as opiates, are used together. The full implementation of treatment, rehabilitation and harm reduction services will reduce the negative health, social and economic consequences of drug use for individuals, communities and society as a whole. The number of drug users will increase, those involved in counseling, treatment, rehabilitation and harm reduction programs [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer (GC) is one of the main causes of death from diseases, especially in developing countries. MicroRNAs (miRNAs) are important modulators of the messenger RNAs expression. Among these miRNAs, MiR-143 is a tumor suppressor miRNA and its irregular expression has been revealed in a diversity of malignancies such as GC. Methods: In this study, we have attempted to restore the miR-143 expression in MKN-45 cells by introducing pCMV-miR-143 plasmid vectors. The consequences of exogenous expression of miR-143 on cell proliferation and migration were assessed by MTT and scratch tests, respectively. In addition, the DAPI staining assay was applied for apoptosisquantification. Following miR-143 transfection, the changes in K-Ras, C-Myc, MMP9, Bax, Caspase-3, and Caspase-9 mRNA levels were assessed. Results: The results indicated that the enhanced expression of miR-143 had negative effects on MKN-45 cells proliferation and invasion. Moreover, decreased expressions of K-Ras, MMP9, and C-Myc and up-regulation of Bax, Caspase-3, and Caspase-9 as downstream targets of miR-143 were recognized. Conclusion: These experimental results indicate that reversing the miR-143 expression, by novel techniques, including miRNA replacement could be considered as an efficient approach to reduce cell survival and metastasis.

Introduction: Hemophilia A is managed with coagulation clotting factor VIII (FVIII) therapy that poses significant challenges, such as a high treatment burden, immunogenicity, inconsistent hemostatic cover, poor treatment outcomes, and musculoskeletal progression despite adequate prophylactic treatment. Various non-factor therapies, such as several natural anticoagulant inhibitors and factor FVIII mimetics, have been developed to address these unmet needs. However, the role of emicizumab in addressing these unmet needs remains underexplored., Areas Covered: This review delves into the evolution of hemophilia A replacement clotting therapy from plasma-derived products to recombinant products and, more recently, nonfactor therapies. It underscores the unmet needs of replacement therapy and explores the nonfactor therapies developed to address them. The review then comprehensively summarizes the clinical trial and real-world experience data, demonstrating how emicizumab tackles these unsatisfied demands., Expert Opinion: Replacement clotting factor therapies as the standard of care has exposed several needs that have yet to be addressed. However, data from numerous emicizumab clinical trials and real-world experience offer a promising outlook, suggesting that it may effectively address many unmet needs. As hemophilia treatment goals continue to evolve, the role of currently developed nonfactor therapies in hemophilia management is yet to be fully defined.

Plasminogen deficiency type 1 (PLGD-1, hypoplasminogenemia) is an ultra-rare, lifelong disease associated with development of fibrinous lesions in multiple organ systems. Depending on lesion location, clinical manifestations of PLGD-1 can result in acute and/or chronic respiratory airway disease which can compromise respiratory function leading to life-threatening events. Early recognition and effective treatment of airway obstruction caused by fibrinous lesions are critical to prevent morbidity due to respiratory compromise. However, physicians may not be familiar with the clinical presentation and management of PLGD-1, causing delays in diagnosis and treatment and potentially contributing to morbidity. Presented here is a case series of one adult and three pediatric patients with severe respiratory complications of PLGD-1 successfully managed by infusions of plasminogen, human-tvmh replacement therapy. Patients' respiratory symptoms were resolved or greatly improved, and treatment was generally well tolerated. In all patients, baseline plasminogen activity was substantially increased with plasminogen replacement therapy administered initially every one to two days followed by extended interval dosing as symptoms were controlled or resolved. All four described cases support the clinical benefit of replacement therapy with plasminogen, human-tvmh in the resolution of life-threatening respiratory complications associated with PLGD-1. Clinical manifestations in addition to respiratory lesions were also improved or resolved with continued treatment., Competing Interests: Authors CN and AS received research funding from Kedrion SpA, authors HM and JP were consultants to Kedrion SpA, and author KT was employed by Kedrion SpA. The authors declare that this study received funding from Prometic Biotherapeutics and Kedrion SpA. The funders had the following involvement in the study: the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, approval of and decision to submit the manuscript for publication. Prometic Biotherapeutics was acquired by Kedrion in October 2021 and merged with Kedrion in 2023. CN: Research funding – Kedrion SpA (legacy Prometic Biotherapeutics). HM: was a consultant to Kedrion SpA and clinical trial investigator (legacy Prometic Biotherapeutics). JP: Consultant to Kedrion, SpA. KT: Current employee of Kedrion, SpA. AS: Research funding – Agios, BioMarin, Bioverativ, Daiichi Sankyo, Genentech/Roche, Glover Blood Therapeutics, Kedrion Biopharma, Novartis, Novo Nordisk, Pfizer, Prometic Biotherapeutics, Takeda, Regeneron, Be Biopharma; Consultancy – Bioverativ, Prometic Biotherapeutics, Novo Nordisk Membership on entity's Board of Directors or advisory committees – Bioverativ, Genentech/Roche, Novo Nordisk, Takeda, Novo Nordisk Hemophilia Foundation Speakers Bureau – Novo Nordisk, Genentech/Roche, Bioverativ. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (© 2024 Nakar, McDaniel, Parker, Thibaudeau, Thukral and Shapiro.)

Background/aim: MicroRNAs play crucial roles in controlling cellular biological processes. miR-143 expression is usually downregulated in different cancers. In this study, we focused on exploring the role of miR143 in NSCLC development. Methods: Bioinformatics analyses were used to detect the expression level of miR-143 in lung tumors. The cells were transfected by pCMV-miR-143 vectors. The efficacy of transfection was verified by Flow cytometry. The influence of miR-143 replacement on NSCLC cells migration, proliferation, and apoptosis was detected using wound-healing assay, MTT assay, and DAPI staining, respectively. Results: MTT assay revealed that overexpression of miR143 inhibited cell growth and proliferation. Scratch assay results demonstrated that restoration of miR143 suppressed cell migration. The qRT-PCR assay was further used to detect the assumed relationship between miR143 and apoptotic and metastatic-related genes. Conclusion: The findings showed that miR-143 could reduce cell proliferation, invasion, and migration by reducing CXCR4, Vimentin, MMP-1, Snail-1, C-myc expression level, and increasing E-cadherin expression levels in lung cancer cells and might be a potential target in NSCLC's targeted therapy. [ABSTRACT FROM AUTHOR]