http://repository.usmf.md:80/handle/20.500.12710/10713 Fri, 25 Sep 2026 20:10:19 GMT 2026-09-25T20:10:19Z http://repository.usmf.md:80/handle/20.500.12710/29004 Title: Assessment of the cases of postpartum hemorrhage in multiparous women Authors: Cemortan, Maria; Bubulici, Cristina; Vicol, Maria-Magdalena; Grajdean, Elena; Scripnic, Gabriela; Manic, Milena Abstract: 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/handle/20.500.12710/29004 2024-01-01T00:00:00Z http://repository.usmf.md:80/handle/20.500.12710/28498 Title: Adeno-associated virus (AAV) - based gene therapies for retinal diseases Authors: Ciolac, Maria Abstract: 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. Description: 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/handle/20.500.12710/28498 2024-01-01T00:00:00Z http://repository.usmf.md:80/handle/20.500.12710/28463 Title: The influence of type 2 pregestational diabetes mellitus on the fetus Authors: Surlaru, Valeria Abstract: Introduction. The prevalence of type 2 diabetes among women of reproductive age is increasing. According to the latest data from the International Diabetes Federation in 2019, one in six live births is affected by hyperglycemia during pregnancy, that represents a risk for the intrauterine development of the fetus, and despite significant advances in glycemic control of pregnancies with diabetes, adverse outcomes for the fetus are still very common. Aim of study. To elucidate the biochemical mechanisms of influence of type 2 diabetes on the intrauterine development of the fetus with the aim of improving diagnosis, treatment and preventing the occurrence of adverse effects. Methods and materials. To achieve the proposed goal, a bibliographic search was performed using 10 bibliographic sources, between the 2018-2023, including those of the Medical Scientific Library of USMF "Nicolae Testemitanu", data of the electronic libraries such as PubMed, MedScape, Medline, Diabetes Care and Diabetologia. Results. Maternal hyperglycemia increases apoptosis in the embryo, which is specifically observed in neuroepithelial cells. An important role also has oxidative stress, which increases the BAX:BCL-2 ratio- indicator of apoptosis level in glioma cells, associated with the increase of cytochrome C in mitochondria and the activation of caspase 3 in embryonic cells. Increased glucose transfer from mother to the fetus induces fetal hyperglycemia, pancreatic β-cell hyperplasia, and consequently fetal hyperinsulinemia (FHI). Insulin influences glucose uptake and lipogenesis via the glucose transporter GLUT-4, expressed in fetal adipose tissue and induces fetal macrosomia. The placenta acts as a passive conduit for maternal glucose to the fetus, especially towards the end of gestation. Therefore, increased glucose transport from diabetic mothers, together with FHI, stimulates fetal triacylglycerol formation and deposition of excess fetal adipose tissue. FHI can delay lung development in the fetus of a diabetic mother. A physiological level of insulin plays a role as a stimulatory hormone in the synthesis of surfactant, but a high level of insulin can inhibit the lipid components of the surfactant: phosphatidylcholine (PC), phosphatidylglycerol (PG) and phosphatidylinositol (PI) and low level of surfactant protein expression.Thus, it decreases the ability of surfactant to reduce alveolar surface tension, increasing the risk of respiratory distress syndrome (RDS). Pregnant women usually have a pathological weight gain, associated with a high production of pro-inflammatory cytokines and adipokines TNF-α, IL-1β, IL-6, responsible for insulin resistance. Conclusion. Maintaining maternal glucose in optimal parameters is essential for the normal development of the fetus by reducing the risk of congenital malformations and preventing postpartum complications. According to the latest data from the International Di abetes Federation in 2019, one in six live births is affected by hyperglycemia during pregnancy, that repr esents a risk for the intrauterine development of the fetus, and despite significant advances in glycemic control of pregnancies with diabetes, adverse outcomes for the fetus are still ver y common. Aim of study. To elucidate the biochemical mechanisms of influence of t ype 2 diabetes on the intrauterine development of the fetus with the aim of improving diagnosis, treatment and preventing the occurrence of adverse effects. Methods and materials. To achieve the proposed goal, a bibliographic search was perfo rmed using 10 bibliographic sources, between the 2018-2023, including those o f the Medical Scientific Library of USMF "Nicolae Testemitanu", data of the electronic libraries such as PubMed, MedScape, Medline, Diabetes Care and Diabetologia. Results. Maternal hyperglycemia increases apoptosis in the embryo, which is specifically observed in neuroepithelial cells. An important role also ha s oxidative stress, which increases the BAX:BCL-2 ratio- indicator of apoptosis level in glioma c ells, associated with the increase of cytochrome C in mitochondria and the activation of ca spase 3 in embryonic cells. Increased glucose transfer from mother to the fetus induces fetal hyperglycemia, pancreatic β-cell hyperplasia, and consequently fetal hyperinsulinemia (FHI). Ins ulin influences glucose uptake and lipogenesis via the glucose transporter GLUT-4, expressed in fetal adipose tissue and induces fetal macrosomia. The placenta acts as a passive conduit for maternal glucose to the fetus, especially towards the end of gestation. Therefore, increased glucose transport from diabetic mothers, together with FHI, stimulates fetal triacylglycerol form ation and deposition of excess fetal adipose tissue. FHI can delay lung development in the fetus of a diabetic mother. A physiological level of insulin plays a role as a stimulatory hormone in the s ynthesis of surfactant, but a high level of insulin can inhibit the lipid components of the surfactant: phosphatidylcholine (PC), phosphatidylglycerol (PG) and phosphatidylinositol (PI) and low level of surfactant protein expression.Thus, it decreases the ability of surfactant to reduce alveolar surface tension, increasing the risk of respiratory distress syndrome (RDS). Pregnant women usually have a pathological weight gain, associated with a high production of pro-inflamm atory cytokines and adipokines TNF-α, IL-1β, IL-6, responsible for insulin resistance. Conclusion. Maintaining maternal glucose in optimal parameters is e ssential for the normal development of the fetus by reducing the risk of congenital malformations and preventing postpartum complications. Description: 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/handle/20.500.12710/28463 2024-01-01T00:00:00Z http://repository.usmf.md:80/handle/20.500.12710/28487 Title: Fundoplication-induced hyperinsulinemic hypoglycemia Authors: Bogdanov, Alan; Louka, George Abstract: 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. Description: 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/handle/20.500.12710/28487 2024-01-01T00:00:00Z