http://repository.usmf.md:80/xmlui/handle/20.500.12710/10713 Sat, 11 Apr 2026 14:27:57 GMT 2026-04-11T14:27:57Z http://repository.usmf.md:80/xmlui/handle/20.500.12710/29004 Assessment of the cases of postpartum hemorrhage in multiparous women Cemortan, Maria; Bubulici, Cristina; Vicol, Maria-Magdalena; Grajdean, Elena; Scripnic, Gabriela; Manic, Milena Introduction. Postpartum hemorrhage (PPH) is one of the leading obstetric complications, affecting 5-15% births. Being a major factor in maternal mortality and morbidity, PPH causes about 25% of maternal deaths worldwide. Aim of study. The aim of the study was to assess the cases of PPH in multiparous women, admitted to the Tertiary Perinatal Center. Methods and materials. The retrospective study was performed by assessing 81 clinical cases of PPH in multiparous women. Total blood loss in labor or C-section was performed by using graduated vessels, and all the sterile material used was weighted. For continuous variables, the mean values and standard deviation of the mean were calculated; the median (Me) as well as the interquartile range (Q1;Q3) in the case of a distribution of characteristics that differs from the normal. Results. The average age of women was 31.6±5.5 years (Me 32 (28;35.5)), varying in the limits of 20-42 years. The majority of participants delivered for the second time - 38 cases (46.9% (95% CI 33.3-59.9)), however, 30 women (37.0% (95% CI 25.9-48.2)) gave birth for the third time, and 13 women (16.1% (95% CI 8.5-27.4)) had 4th – 9th delivery. In 41 cases (50.6% (95% CI 40.7- 61.7)) a c-section was performed. The mean blood loss in vaginal delivery was 850±308 (Me 800 (600;1050)) mL, varying in the limits of 500– 1600 mL. Compared to the mean blood loss in Csection – 1752±1093 (Me 1500 (1100;1850)) mL, varying in the limits of 1000 – 5250 mL. In the structure of PPH there were assessed 26 cases (32.1% (95% CI 20.9-47.0)) of the placental defect or placenta adherens, 15 cases (18.5% (95% CI 10.3-30.5)) of lacerations of the birth canal, 11 cases (13.6% (95% CI 7.4-23.4)) of uterine atonia, and 2 cases (2.5% (95% CI 0-7.3)) of uterine rupture. Hence, in 46 women (56.8% (95% CI 44.6-69.1)) it was applied conservative management of the cases. However, in 20 cases (24.6% (95% CI 15.0-38.1)) an operative management was applied, from which 7 cases (8.6% (95% CI 3.7-14.7)) hemostatic sutures were applied. In 13 cases (16.0% (95% CI 8.5-27.4)) hysterectomy was performed, from which 9 cases (69.2% (95% CI 31.6-100)) subtotal hysterectomy without annexes was the elective method for definitive hemostasis. Conclusion. PPH is a major obstetric complication, which occurs more frequently in multiparous women, in association with placental pathology and birth canal trauma, explained by overextension of the uterus and coagulation disorders, requiring extensive surgical management. Mon, 01 Jan 2024 00:00:00 GMT http://repository.usmf.md:80/xmlui/handle/20.500.12710/29004 2024-01-01T00:00:00Z http://repository.usmf.md:80/xmlui/handle/20.500.12710/28498 Adeno-associated virus (AAV) - based gene therapies for retinal diseases Ciolac, Maria Introduction. Retinal degeneration and macular dystrophies are the leading causes of visual acuity loss and blindness in middle-aged people worldwide. Existing treatment, although considered effective, often does not lead to a complete recovery of the patient, which leads to the need to find new alternatives. It has been proven that genetic factors play an important role in the development of retinal degeneration. Consequently, gene therapy has always been of great interest to scientists as a very promising field of study. Aim of study. The adeno-associated virus has become the vector of choice for retinal diseases. This virus is very compact, has a high tropism to the retina and a relatively low immune response. The increased interest of the scientific community in this area led to the fact that in 2017 the FDA approved a gene therapy for Leber congenital amaurosis caused by the RPE65 mutation. Methods and materials. Hu ML, Edwards TL, O'Hare F, Hickey DG, Wang JH, Liu Z, Ayton LN. Gene therapy for inherited retinal diseases: progress and possibilities. Clin Exp Optom. 2021 May;104(4):444454. doi: 10.1080/08164622.2021.1880863. Epub 2021 Mar 2. PMID: 33689657. Bucher K, RodríguezBocanegra E, Dauletbekov D, Fischer MD. Immune responses to retinal gene therapy using adenoassociated viral vectors - Implications for treatment success and safety. Prog Retin Eye Res. 2021 Jul;83:100915. doi: 10.1016/j.preteyeres.2020.100915. Epub 2020 Oct 15. PMID: 33069860. Botto C, Rucli M, Tekinsoy MD, Pulman J, Sahel JA, Dalkara D. Early and late stage gene therapy interventions for inherited retinal degenerations. Prog Retin Eye Res. 2022 Jan;86:100975. doi: 10.1016/j.preteyeres.2021.100975. Epub 2021 May 29. PMID: 34058340. Ku CA, Pennesi ME. The new landscape of retinal gene therapy. Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):846-859. doi: 10.1002/ajmg.c.31842. Epub 2020 Sep 5. PMID: 32888388. Ail D, Malki H, Zin EA, Dalkara D. AdenoAssociated Virus (AAV) - Based Gene Therapies for Retinal Diseases: Where are We? Appl Clin Genet. 2023 May 30;16:111-130. doi: 10.2147/TACG.S383453. PMID: 37274131; PMCID: PMC10239239. Castro BFM, Steel JC, Layton CJ. AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies. BioDrugs. 2023 Oct 25. doi: 10.1007/s40259-023-00629-y. Epub ahead of print. PMID: 37878215. Results. Despite all the advantages, there are still many obstacles to the effective use of AAV for a wider range of retinal diseases. For example, the small size of AAV particles is also a disadvantage, since the viral capsid has a limited capacity. In addition, although the immune response is considered relatively low, various complications often occur that prevent the full delivery of AAV to the target organ. Conclusion. Gene editing and gene replacement techniques have become a real breakthrough in the treatment of inherited retinal diseases. However, this treatment is effective if it is applied at an early stage of the disease, before the degeneration of photoreceptors. In addition, taking into account the fact that the use of AAV still causes an immune response, it is important to distinguish between an acceptable immune response and a destructive one, which exacerbates the course of the disease and prevents effective treatment. and blindness in middle-aged people worldwide. Existing treatment, although considered effective, often does not lead to a complete recovery of the patient, which l eads to the need to find new alternatives. It has been proven that genetic factors play an important role in the development of retinal degeneration. Consequently, gene therapy has always been of great intere st to scientists as a very promising field of study. Aim of study. The adeno-associated virus has become the vector of choice fo r retinal diseases. This virus is very compact, has a high tropism to the retina and a rel atively low immune response. The increased interest of the scientific community in this area led to the fact that in 2017 the FDA approved a gene therapy for Leber congenital amaurosis caused by the RPE65 mutation. Methods and materials. Hu ML, Edwards TL, O'Hare F, Hickey DG, Wang JH, Liu Z, Ayton LN. Gene therapy for inherited retinal diseases: progress and possibiliti es. Clin Exp Optom. 2021 May;104(4):444454. doi: 10.1080/08164622.2021.1880863. Epub 2021 Mar 2. PMID: 33689657. Bucher K, RodríguezBocanegra E, Dauletbekov D, Fischer MD. Immune responses to retina l gene therapy using adenoassociated viral vectors - Implications for treatment succe ss and safety. Prog Retin Eye Res. 2021 Jul;83:100915. doi: 10.1016/j.preteyeres.2020.100915. Epub 2020 Oct 15. PMID: 33069860. Botto C, Rucli M, Tekinsoy MD, Pulman J, Sahel JA, Dalkara D. Early and late stage gene therapy interventions for inherited retinal degenerations. Prog Retin Eye Res. 2022 Jan;86:100975. d oi: 10.1016/j.preteyeres.2021.100975. Epub 2021 May 29. PMID: 34058340. Ku CA, Pennesi ME. Th e new landscape of retinal gene therapy. Am J Med Genet C Semin Me d Genet. 2020 Sep;184(3):846-859. doi: 10.1002/ajmg.c.31842. Epub 2020 Sep 5. PMID: 32888388. Ail D, Malki H, Zin EA, Dalk ara D. AdenoAssociated Virus (AAV) - Based Gene Therapies for Retinal D iseases: Where are We? Appl Clin Genet. 2023 May 30;16:111-130. doi: 10.2147/TACG.S383453. PMID: 37274131; PMCID: PMC10239239. Castro BFM, Steel JC, Layton CJ. AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Di abetic Retinopathy Therapies. BioDrugs. 2023 Oct 25. doi: 10.1007/s40259-023-00629-y. Epub ahead of print. PMID: 37878215. Results. Despite all the advantages, there are still many obstacles to the effective use of AAV for a wider range of retinal diseases. For example, the small size of A AV particles is also a disadvantage, since the viral capsid has a limited capacity. In addition, although the immune response is considered relatively low, various complications often occur that prevent the full delive ry of AAV to the target organ. Conclusion. Gene editing and gene replacement techniques have become a r eal breakthrough in the treatment of inherited retinal diseases. However, this tr eatment is effective if it is applied at an early stage of the disease, before the degeneration of photoreceptors. In ad dition, taking into account the fact that the use of AAV still causes an immune response, it is important to distinguish between an acceptable immune response and a destructive one, which exacerbates the course of the di sease and prevents effective treatment. Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica Moldova Mon, 01 Jan 2024 00:00:00 GMT http://repository.usmf.md:80/xmlui/handle/20.500.12710/28498 2024-01-01T00:00:00Z http://repository.usmf.md:80/xmlui/handle/20.500.12710/28499 Cystic fibrosis: current therapeutic targets based on symptoms occurred due to specific CFRT gene mutations Caraman, Daniela Introduction. Cystic fibrosis (henceforth CF) is autosomal recessive disease involving mucus and sweat producing cells affecting multiple organs with lungs most severely affected leading to death in 90% of patients . A mutation in Cystic fibrosis trans-membrane conductance regulator (henceforth CFTR) gene changes a protein (a regulated chloride channel), which regulate the activity of other chloride and sodium channels at the cell surface epithelium.This mutation and some others, have attracted much attention in recent years due to significant advances in the pharmacological targeting. However, increasing evidence points to the reduced efficacy of single treatments, thus reinforcing the need to combine several therapeutic strategies to effectively target the multiple basic defect(s).Also mechanistic subdivisions of some of the major classes of mutations can be a good support in order to improve the success of drug-selection strategies. Aim of study. Study about cystic fibrosis manifestation based on classes of CFRT mutations, and get acknowledged about currently approved drugs and exploration of future clinical development pipeline therapeutics for cystic fibrosis, and possible limitations in their use. Methods and materials. Extensive literature search using individual and a combination of key words related to cystic fibrosis therapeutics. Results. Cystic fibrosis is an autosomal recessive disorder results from mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene was identified in 1989, but more than 20 years later, the regulatory mechanisms controlling its complex expression are still not fully understood. Over the years, scientists have used several different ways of grouping these mutations into different classes. The most recent classification system groups mutations by the problems that they cause in the production of the CFTR protein: Protein production mutations (Class 1);Protein processing mutations (Class 2);Gating mutations (Class 3);Conduction mutations (Class 4);Insufficient protein mutations (Class 5) For many of the identified mutations, the disease liability is unknown, but efforts are under way to assess their functional consequence and clinical severity. Respiratory system and GIT are primarily involved but eventually multiple organs are affected leading to life threatening complications. Management requires drug therapy, extensive physiotherapy and nutritional support. Previously, the focus was on symptomatic improvement and complication prevention but recently the protein rectifiers are being studied which are claimed to correct underlying structural and functional abnormalities. Conclusion. The ultimate goal of theratyping is to achieve optimal correction of a specific mutant defect by selecting the most efficacious CFTR modulator(s), including correctors(s), potentiator(s), and/or read-through drugs, or a combination of these drugs. Based on accumulating observations, however, mechanistic subdivisions of some of the major classes of mutations (classes I, II, and III) may be necessary to further improve the success of drug-selection strategies. sweat producing cells affecting multiple organs with lungs most severely affected leading to death in 90% of patients . A mutation in Cystic fibrosis trans-membrane c onductance regulator (henceforth CFTR) gene changes a protein (a regulated chloride channel), which regul ate the activity of other chloride and sodium channels at the cell surface epithelium.T his mutation and some others, have attracted much attention in recent years due to significant advan ces in the pharmacological targeting. However, increasing evidence points to the reduced efficacy of single t reatments, thus reinforcing the need to combine several therapeutic strategies to effectiv ely target the multiple basic defect(s).Also mechanistic subdivisions of some of the major classes of mutat ions can be a good support in order to improve the success of drug-selection strategies. Aim of study. Study about cystic fibrosis manifestation based on classes of CFRT mutat ions, and get acknowledged about currently approved drugs and exploration of future clinica l development pipeline therapeutics for cystic fibrosis, and possible limitations in thei r use. Methods and materials. Extensive literature search using individual and a combination of k ey words related to cystic fibrosis therapeutics. Results. Cystic fibrosis is an autosomal recessive disorder results from mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene was iden tified in 1989, but more than 20 years later, the regulatory mechanisms controlling its comple x expression are still not fully understood. Over the years, scientists have used several different w ays of grouping these mutations into different classes. The most recent classification syste m groups mutations by the problems that they cause in the production of the CFTR protein: Protein production mutations (Class 1);Protein processing mutations (Class 2);Gating mutations (Class 3);Conduction mutations (Cl ass 4);Insufficient protein mutations (Class 5) For many of the identified mutations, the di sease liability is unknown, but efforts are under way to assess their functional consequence and cli nical severity. Respiratory system and GIT are primarily involved but eventually multiple organs are affecte d leading to life threatening complications. Management requires drug therapy, extensive physiot herapy and nutritional support. Previously, the focus was on symptomatic improvement and complication preve ntion but recently the protein rectifiers are being studied which are claimed to correct underlying structural and functional abnormalities. Conclusion. The ultimate goal of theratyping is to achieve optimal correction of a specific mutant defect by selecting the most efficacious CFTR modulator(s), incl uding correctors(s), potentiator(s), and/or read-through drugs, or a combination of these drugs. Based on ac cumulating observations, however, mechanistic subdivisions of some of the major classes of mutations (classes I, II, and III) may be necessary to further improve the success of drug-selection stra tegies. Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica Moldova Mon, 01 Jan 2024 00:00:00 GMT http://repository.usmf.md:80/xmlui/handle/20.500.12710/28499 2024-01-01T00:00:00Z http://repository.usmf.md:80/xmlui/handle/20.500.12710/28487 Fundoplication-induced hyperinsulinemic hypoglycemia Bogdanov, Alan; Louka, George Introduction. Hypoglycemia is often diagnosed in diabetic patients; however, this diagnosis is far rarer in non-diabetic patients. Hypoglycemia in non-diabetic persons is polyetiological. Patients often require an extensive history and array of investigations due to similar clinical presentations with insulinomas. Frequent hypoglycemic episodes in non-diabetic patients with a history of gastric surgery should raise concern for Late dumping syndrome (LDS). Case presentation. A 52-year-old woman was admitted to Republican Clinical Hospital in September 2023 with complaints of tremors, hyperhidrosis, palpitations, headache, foggy vision, fatigue, and low tolerance to exertion. She attributes her symptoms to hypoglycemia. Further workup confirms episodes of low blood glucose (1.3 mmol/l). She states these episodes have been ongoing for the last 5 years. Her medical history highlights the presence of an adrenal tumor and a Nissen fundoplication in 2018. The patient mentions that the hypoglycemic episodes appear 11.5 hours after the intake of food. Available imaging of the abdomen reveals a unilateral adrenal mass and no signs of tumor formation in/around the pancreas. A 72-hour fasting test was conducted and no hypoglycemia was registered. Bloodwork revealed normal C-peptide and insulin levels. Follow-up of the adrenal tumor included metanephrine levels, aldosterone/renin ratio assessment, and low-dose dexamethasone test. Results demonstrate a non-secretory adrenal tumor. The absence of hypoglycemia during the 72-hour fast, coupled with normal insulin and C-peptide levels, excluded an insulinoma, and late dumping syndrome (LDS) was suspected given a history of gastric surgery and postprandial hypoglycemia. Adjustments of the patient's diet subsequently resolved the episodes of hypoglycemia. Discussions. The work-up of a non-diabetic patient with episodic hypoglycemia is complex given the multifactorial etiologies. Things like alcohol or drug administration, liver, renal or primary adrenal failure, neoplasia, insulin/insulin receptor antibodies, insulinomas, and bariatric surgery could lead to hypoglycemia. Evaluation of the patient excluded endogenous hyperinsulinemia and ruled out most causes of hypoglycemia, apart from LDS – a possible adverse effect of the patient’s gastric surgery. Conclusion. This case represents the challenges of diagnosing hypoglycemia in non-diabetic patients. LDS can occur after gastric surgery. Patients experience episodes of postprandial hypoglycemia. A clinician’s awareness of the adverse effects of gastric surgery and patient education on proper diet following surgery may help prevent LDS. rarer in non-diabetic patients. Hypoglycemia in non-diab etic persons is polyetiological. Patients often require an extensive history and array of investiga tions due to similar clinical presentations with insulinomas. Frequent hypoglycemic episodes in non-diabe tic patients with a history of gastric surgery should raise concern for Late dumping syndrom e (LDS). Case presentation. A 52-year-old woman was admitted to Republican Clinical Hospit al in September 2023 with complaints of tremors, hyperhidrosis, palp itations, headache, foggy vision, fatigue, and low tolerance to exertion. She attributes her sym ptoms to hypoglycemia. Further workup confirms episodes of low blood glucose (1.3 mmol/l). She states these episodes have been ongoing for the last 5 years. Her medical history highlight s the presence of an adrenal tumor and a Nissen fundoplication in 2018. The patient mentions that the hypoglycemic episodes appear 11.5 hours after the intake of food. Available imaging of th e abdomen reveals a unilateral adrenal mass and no signs of tumor formation in/around the pancreas. A 72-hour fasting test was conducted and no hypoglycemia was registered. Bloodwork reveal ed normal C-peptide and insulin levels. Follow-up of the adrenal tumor included metaneph rine levels, aldosterone/renin ratio assessment, and low-dose dexamethasone test. Results de monstrate a non-secretory adrenal tumor. The absence of hypoglycemia during the 72-hour fast, coupled wit h normal insulin and C-peptide levels, excluded an insulinoma, and late dumping syndrome (LDS) was suspected given a history of gastric surgery and postprandial hypoglycemia. Adjustments of the patient's diet subsequently resolved the episodes of hypoglycemia. Discussions. The work-up of a non-diabetic patient with episodic hypoglyc emia is complex given the multifactorial etiologies. Things like alcohol or drug administration, liver, renal or primary adrenal failure, neoplasia, insulin/insulin receptor antibodi es, insulinomas, and bariatric surgery could lead to hypoglycemia. Evaluation of the patient excluded endogenous hyperinsulinemia and ruled out most causes of hypoglycemia, apart from LDS – a po ssible adverse effect of the patient’s gastric surgery. Conclusion. This case represents the challenges of diagnosing hypoglyc emia in non-diabetic patients. LDS can occur after gastric surgery. Patients ex perience episodes of postprandial hypoglycemia. A clinician’s awareness of the adverse effe cts of gastric surgery and patient education on proper diet following surgery may help prevent LDS. Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica Moldova Mon, 01 Jan 2024 00:00:00 GMT http://repository.usmf.md:80/xmlui/handle/20.500.12710/28487 2024-01-01T00:00:00Z