Medicine and Pharmacy Reports

The association between exocrine pancreatic insufficiency and changes in gut microbiota: a narrative review

2025-01-31T09:55:08+00:00

Due to their physical proximity, the healthy pancreas and the gut microbiome are known to interact in a variety of ways. The gut microbiota has been recognized as a potential factor in the development and progression of exocrine pancreatic insufficiency through several mechanisms. Pancreatic diseases like chronic and acute pancreatitis or pancreatic cancer are frequently accompanied by pancreatic exocrine insufficiency which affects the gut microbiota. Firstly, the gut microbes are controlled by antimicrobial pancreatic secretions, while themselves induce the secretion of substances by the pancreas through metabolite production, such as short chain fatty acids. Secondly, dysbiosis, the alteration in the abundance and diversity of different species, has been observed in patients with pancreatic diseases. Dysbiosis influences carcinogenesis in pancreatic cancer in ways that are either procarcinogenic or anticarcinogenic and finding these connections will have clinical implications. Identifying microbial biomarkers allow for an earlier diagnosis, improved therapy and prognosis in pancreatic cancer. The gut microbiome has a role in the pathogenesis of pancreatitis by either a bacterial translocation or a host immune response mechanism. The disruption of the normal gut barrier is believed to be the primary source of bacteria in acute pancreatitis which leads to infected pancreatic necrosis.

In this paper, we review the current data about the association between pancreatic diseases linked to exocrine insufficiency and gut microbiota.

The immunomodulatory potential of vitamin D on Th17 lymphocytes in systemic lupus erythematosus - a literature review

2025-01-31T09:55:09+00:00

This review offers insight into the complex interplay between cytokines and vitamin D, with focus on its role in systemic lupus erythematosus (SLE) pathogenesis. It offers a helpful resource for researchers and clinicians seeking to better understand and treat SLE and related autoimmune conditions. The pathogenesis of SLE is complex and involves a wide range of cytokines, primarily of the Th2 type; these cytokines mediate hyperactivity in B lymphocytes and antibody production. Notably, vitamin D is found to suppress the activity of critical Th17-related cytokines like IL-23 and IL-6, which is pivotal for Th17 cell development and function. This ultimately leads to reduced IL-17 production, an increase in regulatory T lymphocytes, and subsequent secretion of IL-10. Supplementation with vitamin D is seen to have positive effects on SLE, leading to lower disease activity scores, decreased levels of autoantibodies, and a reduction of fatigue.

Patient - prosthesis mismatch and its influence on immediate postoperative Von Willebrand factor levels in aortic valve replacement surgery

2025-01-31T09:55:09+00:00

Background and aims. Aortic stenosis (AS) often requires surgical aortic valve replacement (SAVR). Patient-prosthesis mismatch (PPM) can lead to suboptimal outcomes. Von Willebrand factor (VWF), crucial for hemostasis, is altered in AS patients. As part of an ongoing study, this research focuses on the impact of PPM on immediate postprocedural VWF levels in SAVR patients, building upon our previous publication on short-term VWF dynamics in SAVR and TAVR.

Methods. This prospective study included 31 consecutive patients with severe AS undergoing SAVR. Preoperative and postoperative VWF levels were measured. PPM was assessed based on the indexed effective orifice area of the implanted valve.

Results. PPM was observed in 61.29% of patients. Postoperative VWF antigen levels increased significantly (131.37 ± 64.82 IU/dL to 311.01 IU/dL, p<0.01). However, PPM did not significantly influence postoperative VWF antigen levels (285.43 IU/dL vs. 293.30 IU/dL, p=0.88), VWF activity (178.33% vs. 204.76%, p=0.56), or Factor VIII levels (100.38 IU/dL vs. 97.10 IU/dL, p=0.79).

Conclusions. While SAVR led to increased VWF levels, PPM did not impact short-term VWF dynamics. This study provides insights into PPM and VWF relationships in SAVR patients, informing valve selection and perioperative management strategies. A future paper will reveal long-term follow-up results, completing this comprehensive investigation of VWF dynamics in aortic valve interventions.

Impact of CFTR modulatory therapies on liver function and fibrosis indices in cystic fibrosis patients: a retrospective analysis from two Romanian medical centers

2025-01-31T09:55:09+00:00

Background. Patients with cystic fibrosis (CF) frequently require modulatory therapies such as Lumacaftor/Ivacaftor (LI) and Elexacaftor/Tezacaftor/Ivacaftor (ETI) to manage their condition. Given the potential hepatic complications associated with CF, it is critical to understand the impact of these therapies on liver function and fibrosis indices. This study aimed to evaluate the changes in liver function markers and fibrosis indices in CF patients undergoing LI and ETI therapies, with a specific focus on the influence of underlying hepatic disease.

Methods. In this retrospective analysis, liver function markers and fibrosis indices were assessed in CF patients receiving ETI (n=24), LI (n=4), or a combination of both (LI/ETI, n=8). Key liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, platelet count, and fibrosis indices (APRI and FIB-4), were measured at baseline and at various time points up to 12 months.

Results. In patients receiving LI therapy, ALT and AST levels demonstrated a slight but non-significant decrease over six months, accompanied by significant fluctuations in total bilirubin levels. Among those receiving ETI therapy, ALT and AST levels initially increased but stabilized over time, while total bilirubin levels significantly increased from baseline to 12 months. No significant differences were observed in liver function markers between patients with and without hepatic disease under ETI therapy. Trends in fibrosis indices (APRI and FIB-4) were modest and largely non-significant across both therapies.

Conclusions. ETI therapy appears to be safe for CF patients, including those with pre-existing hepatic disease, with no significant deterioration in liver function over a 12-month period. However, the observed fluctuations in bilirubin levels underscore the necessity for ongoing monitoring. Further research is warranted to investigate the long-term hepatic effects of LI and ETI therapies.

Real world outcomes with Ibrutinib monotherapy in Chronic Lymphocytic Leukemia: a single center experience

2025-01-31T09:55:09+00:00

Introduction. The advent of Bruton’s tyrosine kinase (BTK) inhibitors brought about a paradigm shift in the management of chronic lymphocytic leukemia (CLL), by offering a well-tolerated chemotherapy-free approach. Here, we share the experience with ibrutinib of a major Romanian regional cancer center.

Methods. We screened patients treated for CLL in our center over 6 years (2017- 2022) and included those who were treated with ibrutinib either in the first line of therapy or in subsequent lines.

Results. We enrolled 61 patients, 40 with treatment-naïve (TN) CLL and 21 with relapsed/refractory (R/R) CLL, with a median age at treatment initiation of 65 years. Concerning the prognostic-predictive workup, IgHV mutational status was available for 78.7% of the patients, TP53 sequencing for 82%, assessment of 17p deletion for 82%, and CD38 marker analysis was performed for 70.5%. With a median follow-up period of 55 months, the overall response rate (ORR) was 90.2%, with a median progression-free survival (PFS) of 33 months and a median overall survival (OS) that has not been reached. In our cohort, albeit non-significant statistically, patients with TP53 mutation had a shorter OS and those with mutated IgHV, a shorter PFS. Rai 3-4 and Binet C stages at diagnosis were associated with a shorter PFS, but not OS. In our cohort, the correlation between survival and high Cumulative Illness Rating Scale (CIRS) index was not statistically significant. Ibrutinib was generally well tolerated in our cohort, as only 14.8% of our patients discontinued treatment due to adverse effects.

Conclusion. Our study suggests that ibrutinib is a valid therapeutic option for TN or R/R CLL patients, with a high ORR and a good safety profile.

Evaluation of oxidative stress biomarkers for differentiating bacterial and viral infections: a comparative study of glutathione disulfide (GSSG) and reduced glutathione (GSH)

2025-01-31T09:55:09+00:00

Background and aims. This study evaluates the potential of oxidative stress biomarkers, specifically glutathione disulfide (GSSG) and reduced glutathione (GSH), for differentiating bacterial and viral infections. Oxidative stress plays a crucial role in the immune response, and glutathione is a key regulator of cellular redox balance. The aim was to assess whether differences in GSH and GSSG levels could be used as diagnostic markers for infection type.

Methods. A chemiluminescence-based method evaluated GSH and GSSG as potential biomarkers for distinguishing between bacterial and viral infections. The GSH and GSSG concentrations were analyzed across bacterial, viral, and control groups.

Results. Our data revealed significant differences in the GSH/GSSG ratio between the analyzed groups, with bacterial infections showing higher oxidative stress markers compared to viral infections. A combined analysis of GSH and GSSG concentrations, visualized through heatmaps and ROC curves, improved diagnostic accuracy, with clustering patterns distinguishing infection types.

Conclusions. These findings suggest that the GSH/GSSG ratio could be used as a biomarker in distinguishing between bacterial and viral infections, offering potential clinical applications for more accurate diagnosis. Further research is required to validate these results in larger cohorts and to explore the underlying mechanisms of oxidative stress in pathogen-specific immune responses.

Severity, outcomes, and vaccination status in hospitalized children who tested positive for SARS-CoV-2 during two pandemic waves

2025-01-31T09:55:09+00:00

Background. The infection with SARS-CoV-2 in children usually manifests as a mild respiratory tract infection. The aim of this study was to evaluate the severity, outcome and vaccination status in children hospitalized for COVID-19 in a single center during two pandemic waves determined by different SARS-CoV-2 variants of concern (VOCs).

Methods. A retrospective study on 656 consecutive pediatric patients was performed from September 1, 2021, to April 30, 2023. The study interval was divided into waves, according to official data on the circulation of Delta and Omicron VOCs. Data collected included sex, age, comorbidities, date of diagnosis, duration of hospitalization, vaccination status, clinical outcome.

Results. The Delta group consisted of 234 children with a mean age of approximately 9 years, while the Omicron group included 422 children with a mean age of around 2.5 years. Most cases were mild, although in the Omicron wave the hospitalization rate was higher and 41.7% of the cases were medium in severity. The presence of comorbidities was not linked to an increase in severity. Vaccination rates were low in both groups, with a mean of 4% for the total of eligible patients.

Conclusion. This pioneering study highlights the nature of COVID-19 in children, focusing on both clinical aspects and public health issues.

The effects of active and relaxing music on the short-term memory, attention and metabolic parameters of type 2 diabetes patients (T2DM)

2025-01-31T09:55:09+00:00

Objective. Metabolic parameters and cognition are known to be impaired in diabetes, while music seems to have an impact on both. We aimed to study the effects of active and relaxing music on the short-term memory, attention and metabolic parameters of type 2 diabetes patients (T2DM).

Methods. A two-day interventional, within-subject study was carried on 89 T2DM patients treated only with metformin and 67 age- and sex-matched control. The Pieron Toulouse test and Word Recognition Test were used to evaluate attention and short-term memory. The music listened to was the Allegro, respectively the Andante parts of 2 Mozart Sonatas. Cognitive tests, blood pressure and blood

glucose measurements were performed before and after each 20 minutes of music intervention.

Results. Baseline attention performance was better in the control group compared to T2DM (p<0.000). Performance improved significantly in both groups under both types of music, however the last to the first measurement difference was higher in the control group (p=0.04). Female T2DM participants had better improvement under active music (p<0.01). Short-term memory improved during active music, but this was significant only in the control group (p=0.041). Both types of music were associated with significantly lower systolic blood pressure (p=0.00), while relaxing music significantly reduced blood glucose levels (p=0.00).

Conclusion. Our study highlighted the beneficial effect of music on metabolic and cognitive parameters, however, its impact depends on the type of music listened. Furthermore, cognitive scores of T2DM, especially in men, were less influenced by music than those of the control group.

Cognitive decline and diabetes in the clinical setting

2025-01-31T09:55:09+00:00

Objective. The aim of our study was to evaluate the prevalence of cognitive decline in patients with diabetes in the clinical setting and to identify patient characteristics directly associated with this condition. patients with diabetes in the clinical setting and to identify patient characteristics directly associated with this condition.

Methods. In our cross-sectional study, we applied the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to determine cognitive function in 172 diabetic patients, in the clinical setting. We included 120 patients with type 2 diabetes (T2DM), 42 cases with type 1 diabetes (T1DM) and 10 patients with confirmed secondary diabetes (SDM). The mean age of the participants was 62.4 years (±1.01, min: 26 years, Max: 87 years), with median diabetes duration of 15±11.8 years.

Results. More than half (55.23%) of the subjects presented cognitive deterioration, which was diabetes type-specific (p<0.05). Mild forms affected mostly T1DM and SDM cases (31.5% and 30% vs. T2DM: 14.5%, p=0.00), whereas moderate cognitive decline was more predominant in T2DM (21.9% vs. T1DM: 7.1%, p=0.1). A higher prevalence of severe cognitive impairment was present in T1DM (14.5% vs. T2DM: 8.7%, p=0.1).

The middle-aged category (40-64 years) was characterized by a more significant reduction of cognitive function in comparison with other age groups (p=0.02).

No gender-related difference in the prevalence of cognitive decline was found (female: 45.83% vs male: 45.71%, p=0.98), although severe forms were significantly more suggestive for men (15.27% vs. 4.18%, p=0.04).

Diabetic ketoacidosis (DKA) at admission was more frequently associated with cognitive deterioration, in comparison with hypoglycemic events (p=0.03).

In T2DM, cognitive decline (p=0.006, r=-0.342) was associated with the presence of anemia.

In T2DM women, treatment with calcium-channel blockers facilitated cognitive decrement (p=0.01, r=-0.339), whereas in men, therapy for distal symmetric polyneuropathy resulted in higher MMSE/ MoCA test scores (p=0.00, r=0.72).

In T1DM, a higher glycemic burden evidenced by increased HbA1c (p=0.03, r=- 0.364) and glycemia at admission (p=0.01, r=-0.389) was suggestive to a more severe form of cognitive impairment. Distal symmetrical polyneuropathy (p=0.05, r=-0.305) and diabetic retinopathy (p=0.03, r=-0.102) was often co-occurring with cognitive decline.

Cognitive deterioration was associated with insulin therapy (p=0.05, r=-0.232).

Conclusion. The prevalence of cognitive decline is high in the diabetic population. Risk stratification must start at diagnosis and physicians should follow disease progression periodically, with special attention attributed to T1DM and the middle-aged population.

The relationship between anxiety, depression, and COVID-19 diagnosis in term pregnancy: a hospital-based Romanian study

2025-01-31T09:55:10+00:00

Background and aim. There are few published data on the mental health problems of women with pregnancy complicated by SARS-CoV-2 infection. Our study aimed to evaluate anxiety and depression related to a COVID-19 diagnosis in women who gave birth in a Romanian tertiary maternity.

Methods. A hospital-based cross-sectional study was conducted between September 2020 and October 2021 on 105 women admitted for term delivery; 51 women were diagnosed with SARS-CoV-2 infection just before delivery, and 54 without infection. Participants were assessed during the first 72 hours postpartum (T1) and the following two weeks postpartum (T2). Hospital Anxiety and Depression Scale (HADS) was used for anxiety and depression assessment at T1. The COVID-19 Pandemic Mental Health Questionnaire (CoPaQ) was applied at T2 only in the COVID-positive cases identified at T1.

Results. Postnatal anxiety levels were higher in COVID-positive women compared to COVID-negative women (p = .004), but there were no differences in the postnatal depression level between the groups. Psychological manifestations related to the pandemic, such as contamination anxiety, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD) symptoms, were positively related to HADS anxiety scores, while maintaining social relationships were negatively associated with the scale. The COVID-19 diagnosis was found to be a significant predictor for adverse pregnancy outcomes (APOs), with COVID-positive women having a 4.72-fold higher risk of developing them than those who tested COVID-negative (OR=4.72, 95% CI [2.05; 10.86]). The multivariate analysis using anxiety and depression as dependent variables indicated a significant effect for COVID-19 diagnosis, Wilks’ Lambda = 0.940, p = 0.048.

Conclusion. Increased levels of anxiety, PTSD, and obsessive-compulsive symptoms were associated with the postpartum period in pregnant women with COVID-19 infection during delivery. Maintaining social interaction proved to be a protective factor against the increased anxiety reported by COVID-19-infected women.

Umbilical cord blood collection through elective cesarean section in an ovine model – a pilot study

2025-01-31T09:55:10+00:00

Background. Despite advancements in congenital heart surgery, long-term outcomes remain challenging, with many patients developing heart failure and requiring transplants at a young age. Stem cell therapy, particularly using umbilical cord-derived mesenchymal stem cells, is emerging as a promising adjunct treatment. Adult studies suggest functional improvements, but pediatric research remains sparse. This pilot study aimed to establish surgical and anesthetic protocols for elective cesarean section in an ovine model to enable umbilical cord blood collection.

Methods. Three pregnant sheep aged 2–6 years and weighing 40–45 kg underwent elective cesarean section. Gestational age was confirmed using ultrasound and clinical signs. Preoperative preparation involved fasting, dexamethasone administration to prevent respiratory distress, and shaving surgical sites. Local anesthesia and mild sedation (medetomidine) minimized fetal exposure to anesthetics. Two umbilical cord blood collection methods were tested: active aspiration and gravitational collection.

Results. We established efficient anesthetic and surgical protocols for elective cesarean section and described a safe and easy method for umbilical cord blood collection with minimal risk. Elective cesarean section ensures a sterile environment, crucial for stem cell isolation. Local anesthesia with mild sedation proved safe and provided proper comfort for animals and operators. Accurate gestational estimation and effective postnatal care were critical.

Conclusions. This study provides a reliable protocol for elective cesarean section and umbilical cord blood collection in an ovine model, offering a valuable foundation for research in stem cell therapy. However, larger sample sizes are needed to validate these methods and enhance their applicability in translational research.

Assessing the quality of life of schizophrenia patients and their family caregivers in a Romanian sample: the role of clinical, sociocultural, and demographic factors

2025-01-31T09:55:10+00:00

Background. Schizophrenia is a chronic mental health disorder significantly impacting the Quality of Life (QOL) of both patients and their family caregivers. In Romania, approximately 193,000 individuals are affected by schizophrenia, with most relying on non-professional family caregivers. These caregivers face substantial psychological, physical, financial, and social challenges, which remain understudied and often overlooked by health policymakers. This research employs a biopsychosocial framework to explore the interconnected clinical, cognitive, and sociocultural factors influencing the QOL of schizophrenia patients and their caregivers.

Objectives. This study aims to assess the QOL of schizophrenia patients and their family caregivers in a Romanian sample, focusing on key determinants such as social support, financial stressors, and caregiving burden, to provide insights for interventions and possibly policy development.

Methods. This cross-sectional study included 156 individuals: 52 schizophrenia patient-family caregiver pairs (n = 104) and a control group of 52 participants recruited from an occupational health clinic. The control group was matched with the patient-caregiver pairs on demographic characteristics, including age, gender, education, and socioeconomic status. Controls were selected to reflect similar socioeconomic and health-related challenges but excluded individuals with a history of mental health disorders. Schizophrenia diagnoses were established using ICD-10 criteria (F20.0– 9). QOL was assessed using the Heinrichs-Carpenter Quality of Life Scale (QLS) exclusively for schizophrenia patients, while the WHOQOL-BREF was administered to all participants to ensure comparability. Additional assessments included the Beck Depression Inventory (BDI) for depressive symptoms, the Montreal Cognitive Assessment (MoCA) for cognitive functioning, the Eppendorf Schizophrenia Inventory (ESI) for caregiver psychopathology, and the Global Assessment of Functioning (GAF) scale to measure functional status.

Results. Caregivers exhibited elevated depressive symptoms, with a mean Beck Depression Inventory (BDI) score of 25 (≥20 indicates moderate depression), highlighting the significant psychological burden associated with caregiving. In contrast, the control group had a mean BDI score of 15, below the clinical threshold. Additionally, caregivers demonstrated reduced cognitive functioning, with a mean Montreal Cognitive Assessment (MoCA) score of 24, compared to 28 in the control group (<26 suggests mild cognitive impairment). These findings underscore the biopsychosocial stressors faced by caregivers.

Conclusions. This study highlights the significant cognitive, psychological, and sociocultural burdens associated with schizophrenia for patients and caregivers, advancing understanding of these challenges in a Romanian context. By emphasizing the need for integrated, culturally sensitive care models, our findings offer actionable insights to inform national and international mental health policies and future research on caregiver support and QOL enhancement.

Cost-effectiveness analysis of the 13-valent pneumococcal conjugate vaccine administered to children under 5 years of age in the Republic of Moldova

2025-01-31T09:55:10+00:00

Background. The Moldovan health authorities introduced the 13 valent pneumococcal conjugate vaccine into the national immunization schedule for children in 2013. This study aimed to evaluate the cost-effectiveness of the pneumococcal conjugate vaccine compared to a no-vaccination strategy in children under 5 Years of age in the Republic of Moldova.

Methods. We used UNIVAC (version 1.7), a static decision model, to evaluate the health and economic outcomes of vaccination in a single-cohort of children under five years. We modeled vaccine introduction over 10 birth cohorts starting in 2013. We assumed a 2+1 (two doses + booster) schedule and a vaccination price of US$ 16.34 per dose. We used locally-specific data for pneumonia incidence, mortality, treatment, and costs. Model outcomes included pneumonia cases, hospitalizations, deaths, disability-adjusted life years, and costs presented in USD. Cost-effectiveness was reported as Incremental Cost Effectiveness Ratio. The Incremental Cost Effectiveness Ratio was calculated to estimate the additional cost to save an additional life year.

Results. From the governmental health sector the Incremental Cost Effectiveness Ratio was $5939 and from society perspective, $7272, respectively. Withal cost per disability-adjusted life years (DALY) averted was US$ 6311. PCV-13 was projected to prevent 2310 hospitalizations due to pneumococcal disease, including 118 deaths. Vaccination could potentially reduce the highest treatment cost from the payer perspective at $ 4 081 412 for the 13 valent pneumococcal conjugate vaccine.

Conclusion. This study evidenced that cost per DALY averted is US$ 6311, which is between one and three times Gross Domestic Product (GDP) per capita, these findings extrapolate PCV-13 as a cost-effective intervention. Considering the scenario of Republic of Moldova the PCV program is a cost effective intervention and justifies the introduction of PCV into routine immunization schedule throughout the country in order to reduce morbidity and mortality among the under-five-year-old children.

Assessing personal and health system barriers to breast cancer early diagnosis practices for women over 20 years old in Cluj-Napoca, Romania

2025-01-31T09:55:10+00:00

Background and aims. Breast cancer diagnosis is established late in Romania. This led to 3918 potentially avoidable deaths by breast cancer in 2020. Statistics show that women seldom perform monthly breast self-examinations or mammographies. This research aims to identify personal and health system barriers to breast cancer screening, with the purpose of enabling participation in future breast screening programs.

Methods. A quantitative cross-sectional, online survey of a convenience sample of 184 women aged 20-65 years old from Cluj-Napoca, Romania was used to evaluate the practice of breast self-exam and ammographies and personal and health system barriers against them.

Results. The sample’s mean age was 34.73 years (SD=11.31, range 20-65). Women in the sample had a high level of education, most holding a Master’s degree (36.4%). The majority declared practicing breast self-examinations from time to time (57.2%) and only (35.5%) did it monthly as per existing guidelines. Personal barriers to breast examination were lack of knowledge (16.3%) and mistrust in self examination (10.3%). Women with higher education engaged in the examination of the breast at least once (X2= (0.047, N = 184), p = 0.003, (CI 95%: 5.515–6.773). Concerning health system barriers, access to information from public health authorities on the availability of mammographies was rated very poor (21.7%). The cost was not a significant barrier to mammographies for 72.8% of the women in the sample.

Conclusions. Our study contributes to the limited data on preventive practices for breast cancer in Romania, the EU country that ranks last for breast control among females and where 13% of the 9000+ cases diagnosed annually are stage IV cancers. Based on the reported factors of a successful breast cancer screening program by our sample, we suggest valuable insights to be taken into consideration when organizing a future breast screening program. Both personal and system barriers to breast self-exam and mammographies must be considered in organizing breast cancer screenings. The focus should be on educational initiatives to improve women’s knowledge about the process of self-screening and on improving access to information on the availability of free screening and mammograms as part of a well-promoted screening program designed with a simple enrolment process.

Identification of urinary metabolites correlated with tacrolimus levels through high-precision liquid chromatography-mass spectrometry and machine learning algorithms in kidney transplant patients

2025-01-31T09:55:10+00:00

Background and aim. Tacrolimus, a widely used immunosuppressive drug in kidney transplant recipients, exhibits a narrow therapeutic window necessitating careful monitoring of its concentration to balance efficacy and minimize dose-related toxic effects. Although essential, this approach is not optimal, and tacrolinemia, even in the therapeutic interval, might be associated with toxicity and rejection within range. This study aimed to identify specific urinary metabolites associated with tacrolimus levels in kidney transplant patients using a combination of serum high-precision liquid chromatography-mass spectrometry (HPLC-MS) and machine learning algorithms.

Methods. A cohort of 42 kidney transplant patients, comprising 19 individuals with high tacrolimus levels (>8 ng/mL) and 23 individuals with low tacrolimus levels (<5 ng/mL), were included in the analysis. Urinary samples were subjected to HPLC-MS analysis, enabling comprehensive metabolite profiling across the study cohort. Additionally, tacrolimus concentrations were quantified using established clinical assays.

Results. Through an extensive analysis of the HPLC-MS data, a panel of five metabolites were identified that exhibited a significant correlation with tacrolimus levels (Valeryl carnitine, Glycyl-tyrosine, Adrenosterone, LPC 18:3 and 6-methylprednisolone). Machine learning algorithms were then employed to develop a predictive model utilizing the identified metabolites as features. The logistic regression model achieved an area under the curve of 0.810, indicating good discriminatory power and classification accuracy of 0.690.

Conclusions. This study demonstrates the potential of integrating HPLC-MS metabolomics with machine learning algorithms to identify urinary metabolites associated with tacrolimus levels. The identified metabolites are promising biomarkers for monitoring tacrolimus therapy, aiding in dose optimization and personalized treatment approaches.

Implications of type 1 diabetes mellitus in the etiology and clinic of dento-maxillary anomalies - questionnaire-based evaluation of the dentists’ opinion

2025-01-31T09:55:10+00:00

Background and aims. Type 1 diabetes is one of the most common chronic childhood diseases, which can be diagnosed at any age, with implications on the general development, but also on the craniofacial structure. It is widely speculated that diabetes occurs when inherited genetic characteristics are triggered by environmental factors. Oral pathology is complex and it includes a series of clinical entities: dental caries, periodontal disease, dento-maxillary anomalies, diseases of the oral mucosa, which implies a significant responsibility for the doctor, but also for society. This study aims to highlight the association of dento-maxillary anomalies with juvenile diabetes, starting from its increased prevalence among children and adolescents, the oral manifestations of diabetes mellitus and its influence on the oral microbiome, the increased incidence of periodontal and dental diseases, by means of a questionnaire.

Method. A cross-sectional study was carried out on a number of 60 dentists, between 01.01.2023 and 01.03.2024, using a questionnaire with 14 items, which was distributed by e-mail and social networks to dentists of different specialties, from various university. Before completing the questionnaire, the doctors were informed about the purpose of the study and that their answers were anonymous and did not imply any responsibility.

Results. Our results indicated awareness of the association between oral health, the presence of dento-maxillary anomalies and the pathology of type 1 diabetes, among dentists of different specialties. The most frequent changes that occur in the oral cavity in the examined patients are represented by carious lesions, reported by 21 examiners (35.00%), of which 18 (39.13%) are female, aged between 25-35 years.

Among the reported dentomaxillary anomalies, those of Angle class II were the most frequent - 17 examiners (28.33%), of which 12 (26.09%) are female reported the presence of these anomalies. The presence of Angle class I anomalies was reported by 13 examiners (21.67%) of which 9 (19.57%) are female, while 6 examiners (10.00%) reported the presence of Angle class III anomalies.

Conclusions. The evaluation of modern therapeutic methods through questionnaires distributed online represents a feedback of the tested activity and shows that most doctors know the correlations between diabetes and oro-dental diseases and have an obvious healthy attitude. The possible association between oral diseases and the presence of type 1 diabetes was reported by most of the dentists interviewed, however the information on the correlations between oral health and the presence of type 1 diabetes in children was not sufficiently explored by dentists. The dentist must know the clinical particularities of diabetes mellitus and its implications on the oral status, in order to be able to intervene effectively in reducing the oral and systemic complications of diabetes.

Severe hypocalcaemia and hypophosphatemia following Denosumab administration in a multi-comorbidity patient

2025-01-31T09:55:08+00:00

The case is presented of an elderly patient (DCP) with extensive medical history, including osteoporosis, who developed hypocalcaemia and hypophosphataemia whilst treated with denosumab, while prescribed concomitant calcium and vitamin D therapies. The management of this complex case involved a multidisciplinary team (MDT) approach, incorporating the patient’s wishes. It included discontinuation of denosumab and intravenous (IV) and oral mineral supplementation that yielded gradual amelioration of calcium and phosphate levels. This case demonstrates the importance of vigilant monitoring and appropriate management in patients receiving denosumab, particularly those with multiple comorbidities. It carries important considerations for using denosumab for osteoporosis treatment in patients with complex medical backgrounds. Ethical clearance waiver was granted by the Trust Research Ethics Committee on 18/01/2024.

Clinical and ultrasonographic evaluation of breast lipofilling after expander extrusion. Case report

2025-01-31T09:55:09+00:00

Background. Breast cancer treatment often involves mastectomy and adjuvant therapies such as radiotherapy, which can lead to complications in reconstructive procedures. Tissue expanders are commonly used for immediate breast reconstruction post-mastectomy, but radiation therapy increases the risk of complications like expander extrusion. Lipofilling has emerged as a promising technique to address tissue damage and improve reconstructive outcomes. This case illustrates the utility of ultrasonography in measuring fat thickness before and after the lipofilling procedure and calculating the resorption rate for managing complex post-radiation complications.

Case description. We report the case of a 38-year-old patient born and raised in Romania with a history of right breast cancer, who initially underwent mastectomy followed by immediate reconstruction with a subpectoral tissue expander. The patient subsequently received adjuvant radiotherapy, which led to the extrusion of the tissue expander and chronic pain with skin redness. Due to significant damage to the surrounding tissue and chest wall, lipofilling was employed as a reconstructive approach to enhance skin quality and support tissue regeneration. Fat grafting was performed in multiple sessions, with ultrasonographic evaluations conducted before and after each session to monitor volumetric changes in the reconstructed breast. Following lipofilling, the patient experienced marked improvements in skin texture and breast volume, with no recurrence of complications. Later that year we performed a DIEP flap.

Conclusions. This case demonstrates the efficacy of ultrasonography in measuring fat graft and fat resorption after lipofilling as a reconstructive strategy in patients who experience complications from tissue expander extrusion post-radiation. Lipofilling, in combination with thorough imaging assessments, can significantly enhance the outcomes of breast reconstruction following radiotherapy.

Dimitrie Cantemir (1683-1723) and his important contribution to the history of inguinal hernia repair

2025-01-31T09:55:08+00:00

In 2023 we celebrated 350 years since the birth, and 300 years since the death of Dimitrie Cantemir (1673-1723), scholar of European prominence, encyclopedic spirit, Prince of Moldavia, first Romanian member of the Berlin Academy of Sciences, and the first in Eastern Europe. Cantemir described for the first time the transperitoneal approach to inguinal hernia repair in his famous work “The History of the Growth and Decay of the Othman Empire”. The work was written in Latin, revised in 1714-1716 and translated into English by N. Tindal and published in 1734. We briefly present a history of the main existing therapeutic procedures for inguinal hernia repair until the Cantemir’s presentation. The description of the procedure is in “Annotationes”, in the chapter entitled “Avlonia”, a region from Albania. The Albanians were famous for their skill in repairing inguinal hernias. Cantemir witnessed a hernia repair performed on his secretary in his palace in Istanbul. He gives a detailed description of the procedure, the abdominal incision, reduction of hernial sac content, closing and cauterizing of the hernial orifice with the preservation of the testicle, and the evolution of the patient during the 30 days of follow-up. The postoperative mortality was 1-2%. The surgical technique presented was a progress towards the operations practiced at the time in Europe, mainly cautery and castration. The history of inguinal hernia repair is a mirror of surgical history. The presentation of the transperitoneal approach of the inguinal hernia by the Romanian scholar is of a great importance for the history of surgery and medicine.

Reviewers list for year 2024

2025-01-31T10:05:38+00:00