Classic and molecular cytogenetic findings in leukemia patients from the Western part of Romania.

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in childhood and rare in adults, while acute myeloid leukemia (AML) is less common in children and more common in older adults. The aim of the study was to present our experience for the diagnostic of leukemia by using the classic and molecular cytogenetic methods. The study was conducted between 2009 and 2019 within the Classic and Molecular Genetic Laboratory of the Oncohematology Department from the Louis Turcanu Emergency Hospital for Children, Timisoara, Romania. The study group included 337 children and adults, evaluated between 2009 and 2019. By using the conventional and molecular cytogenetic technique, the cytogenetic anomalies found were 35 numerical chromosomal abnormalities, 10 (9;22)(q34;q11) [four ALL, one AML, five chronic myeloid leukemia (CML)] translocations, nine (15;17)(q24;q21) translocations, three (14;14)(q11;q32) translocations, two (4;11)(q21;q23) translocations, one (1;14)(p32;q11) translocation, one (7;14)(qter;q11) translocation, one (8;21)(q22;q22) translocation, one (9;14)(p12;q32) translocation, seven rearrangements of the MLL gene and two rearrangements of the core-binding factor subunit beta∕myosin heavy chain 11 (CBFB∕MYH11) gene. The use of conventional and molecular cytogenetic analysis is one of the most important prognostic indicators in acute leukemia patients, allowing the identification of biologically distinct subtypes of disease and selection of appropriate treatment approaches.

A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis.

Background: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. Objective: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Methods: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. Results: A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 - 0.84). Conclusions: We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted.

Active Case-Finding: An Effective Solution for Tuberculosis Detection in Vulnerable Groups - The Romanian Experience.

Introduction: Tuberculosis (TB) remains a global health challenge, requiring enhanced active case finding (ACF) through screening strategies. This study assesses the effectiveness of such an approach in locating TB cases among vulnerable groups, such as homeless persons, injecting drug users, those detained in prison, and people living in rural areas. Methods: The study focuses on socio-economic characteristics and TB detection rates across Romanian counties using modern techniques including computer-aided detection of lesions on chest X-ray and GeneXpert tests. Results: The results highlight the disproportionate burden of TB in vulnerable groups, by revealing significant differences in TB detection rates between regions. Notably, the TB detection rates among these vulnerable groups (250.85 per 100,000 population) are five times higher than the national incidence rate (46.1). Discussion: These findings underscore the imperative integration of ACF into National TB Program to provide customized and efficient solutions for diverse vulnerable groups, thereby informing crucial public health initiatives and interventions.

Ammonia measurement in human breath of subjects with Helicobacter pylori using photoacoustic spectroscopy.

Helicobacter pylori (H. pylori) is a type of bacteria that infects the stomach. The detection of H. pylori is an essential part of current clinical practices because this disease can cause peptic ulcers, chronic inflammation of the stomach lining but also stomach cancer. Helicobacter pylori has a naturally occurring enzyme that hydrolyzes urea into ammonium carbonate called urease. Many methods exist for the detection of H. pylori infection, but an innovative approach is to detect the ammonia in the breath (ABT, Ammonia Breath Test). In this research study, using photoacoustic spectroscopy method, the ammonia concentration in the breathing zone of people with H. pylori were measured and were compared with ammonia concentration from the respiration of healthy people. From the ABT determinations of this study, the ammonia was established to be increased with 498 ppb at people with H. pylori when we compare with ABT of healthy people.

Integrative Approaches for the Diagnosis and Management of Erosive Oral Lichen Planus.

Erosive oral lichen planus (EOLP) represents a significant challenge in dental and medical management due to its chronic inflammatory nature, painful symptoms, and impact on quality of life. This study aims to evaluate the current diagnostic approach with novel non-invasive techniques, such as dermoscopy, and also the landscape of treatment options for EOLP, focusing on its efficacy, safety, and the challenges that it present in clinical practice. Through a comprehensive literature review, we explored the use of topical corticosteroids, systemic immunosuppressants, biologics, and Janus kinase (JAK) inhibitors in treating EOLP, alongside examining patient compliance, psychological impacts, and the risk of adverse effects and recurrence. Our findings reveal that while topical corticosteroids are the cornerstone of EOLP treatment, offering symptomatic relief, their long-term use is limited by side effects and tolerance development. Systemic therapies and biologics provide alternatives for refractory cases but necessitate careful adverse effect monitoring. JAK inhibitors show promise as an innovative treatment avenue but require more evidence on long-term safety and efficacy. This study highlights the necessity of personalized treatment approaches due to the variable disease course and response to treatment, underscoring the importance of a multidisciplinary strategy in managing EOLP. The complexity of EOLP treatment, compounded by its psychological and quality of life impacts, demands ongoing research into targeted therapies, the establishment of standardized treatment protocols, and the development of effective outcome measures to improve patient care and treatment outcomes.

Rare within Rare: A Girl with Severe Haemophilia A and Turner Syndrome.

A coincidental occurrence of severe haemophilia A and Turner syndrome in a female person is extremely rare (less than 10 cases published). In such challenging cases, a multidisciplinary approach based on medicine of precision with full access to genetic and bio-molecular exploration is indispensable. The article presents an eight-year-old girl, with a family history of haemophilia, without significant disease signs (only post-dental extraction bleeding and a shorter stature). Discordantly, however, the investigations revealed a challenging condition: a genotype of 46,X,i(Xq), with an Isochromosome Xq responsible for the Turner syndrome and simultaneously, for the detrimental transformation, interfering with X chromosome inactivation, of an obligate hemophilia carrier into a severe hemophilia case-two distinct and provocative diseases.

Identification of Absorption Spectrum for IED Precursors Using Laser Photoacoustic Spectroscopy.

Among the many commonly encountered hazards, improvised explosive devices (IEDs) remain the primary threat to military and civilian personnel due to the ease of their production and the widespread availability of their raw materials and precursors. Identifying traces of potential precursors is the first step in developing appropriate control measures. An interesting approach is to identify the precursors that are released around the site as they are handled and transformed into the final IEDs. CO2 laser photoacoustic spectroscopy can offer the spectral characterization of a number of explosives-related compounds without sample preparation. Benzene, toluene, acetone, and ethylene glycol absorption spectra were determined in the IR region between 9.2 and 10.8 µm. Each substance emitted a unique photoacoustic response corresponding to its chemical composition that could be further used to identify the explosive material.

Evaluation and Management of Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy complicate up to 10% of pregnancies and remain the major cause of maternal and neonatal morbidity and mortality. Hypertensive disorders of pregnancy can be classified into four groups depending on the onset of hypertension and the presence of target organ involvement: chronic hypertension, preeclampsia, gestational hypertension, and superimposed preeclampsia on chronic hypertension. Hypertension during pregnancy is associated with a higher risk of cardiovascular disease and kidney failure. Early diagnosis and proper treatment for pregnant women with hypertension remain a priority since this leads to improved maternal and fetal outcomes. Labetalol, nifedipine, methyldopa, and hydralazine are the preferred medications to treat hypertension during pregnancy. In this comprehensive review, we discuss the diagnostic criteria, evaluation, and management of pregnant women with hypertension.

NIR and THz spectroscopy: An experimental investigation toward nicotine-related devices.

This study examined the content of nicotine-delivery products using terahertz time-domain spectroscopy (THz-TDS) and breath ethylene investigated with CO2 laser photoacoustic spectroscopy (CO2 LPAS) system as a biomarker of oxidative stress after smoking. The THz-TDS method provided valuable information on the transmission spectra of tobacco and nicotine in smoking products. From the CO2 LPAS data it was observed that in cigarette (TC) smoking the mean breath ethylene was 687 parts per billion (ppb), while in electronic cigarettes and tobacco heating devices smoking the mean ethylene was 56 ppb and 48 ppb, respectively. The main finding was that TC showed higher transmission in the THz region producing a higher oxidative stress on the body.

The Cracking Behavior of Two Dental Composite Materials Validated through Multifractal Analyzes.

The aim of this in vitro study was to analyze, both experimentally and theoretically, the mechanical behavior of two types of composite materials used in restoring dental integrity. The samples of each composite resin, namely Filtek Supreme XT (3M ESPE, St. Paul, MN, USA) and Filtek Z250 (3M ESPE, St. Paul, MN, USA), were experimentally analyzed by determining their compressive strength and fracture behavior. The fractured fragments of the samples were subjected to surface evaluation by scanning electron microscopy. The compressive stress-compressive strain dependencies revealed stronger cracking of the Filtek Supreme XT composite than Filtek Z250 prior to fracture. Theoretically, the evaluation was made by means of holographic implementations of such types of composite materials. A Hooke-type equation in a differential form is presented, which links the proposed theoretical model with the experimentally obtained data.

Pregnancy Outcomes, Immunophenotyping and Immunohistochemical Findings in a Cohort of Pregnant Patients with COVID-19-A Prospective Study.

(1) Background: SARS-CoV-2 infection during pregnancy could determine important maternal and fetal complications. We aimed to prospectively assess placental immunohistochemical changes, immunophenotyping alterations, and pregnancy outcomes in a cohort of patients with COVID-19; (2) Methods: 52 pregnant patients admitted to a tertiary maternity center between October 2020 and November 2021 were segregated into two equal groups, depending on the presence of SARS-CoV-2 infection. Blood samples, fragments of umbilical cord, amniotic membranes, and placental along with clinical data were collected. Descriptive statistics and a conditional logistic regression model were used for data analysis; (3) Results: Adverse pregnancy outcomes such as preterm labor and neonatal intensive care unit admission did not significantly differ between groups. The immunophenotyping analysis indicated that patients with moderate-severe forms of COVID-19 had a significantly reduced population of T lymphocytes, CD4+ T cells, CD8+ T cells (only numeric), CD4+/CD8+ index, B lymphocytes, and natural killer (NK) cells. Our immunohistochemistry analysis of tissue samples failed to demonstrate positivity for CD19, CD3, CD4, CD8, and CD56 markers; (4) Conclusions: Immunophenotyping analysis could be useful for risk stratification of pregnant patients, while further studies are needed to determine the extent of immunological decidual response in patients with various forms of COVID-19.

The Influence of Maternal KIR Haplotype on the Reproductive Outcomes after Single Embryo Transfer in IVF Cycles in Patients with Recurrent Pregnancy Loss and Implantation Failure-A Single Center Experience.

(1) Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) have in common a deficient maternal adaptation to the semi-allogeneic fetus, in which killer immunoglobulin-like receptor (KIR) family expressed by natural killer (NK) cells play an important role. The aim of this study was to evaluate the influence of maternal KIR haplotype on the reproductive outcomes after single embryo transfer in IVF cycles in patients with RPL and RIF. (2) Methods: Patients with RIF and RPL who presented at Origyn Fertility Center from Iasi, Romania, were prospectively enrolled between January 2020 and December 2022. Clinical and paraclinical data was examined. Descriptive statistics and a conditional logistic regression model were used to analyze our data. (3) Results: Patients with a KIR AA haplotype had significantly more chances of miscarriage if they underwent an IVF procedure (aOR: 4.15, 95% CI: 1.39-6.50, p = 0.032) compared with those who spontaneously achieved a pregnancy. Moreover, it appeared that the same haplotype increased the chances of obtaining a pregnancy for patients who underwent an IVF procedure (aOR: 2.57, 95% CI: 0.85-6.75, p = 0.023). (4) Conclusions: Determination of KIR haplotype could be beneficial for patients with RPL or RIF in order to offer an individualized management.

Gut Microbiota in Chronic Kidney Disease: From Composition to Modulation towards Better Outcomes-A Systematic Review.

BACKGROUND: A bidirectional kidney-gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. MATERIALS AND METHODS: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. RESULTS: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls (AUC = 0.771 and AUC = 0.803, respectively). Roseburia abundance was consistently decreased in CKD patients, especially in those with ESKD (p < 0.001). A model based on 25 microbiota dissimilarities had an excellent predictive power for diabetic nephropathy (AUC = 0.972). Several microbiota patterns were observed in deceased ESKD patients as compared to the survivor group (increased Lactobacillus, Yersinia, and decreased Bacteroides and Phascolarctobacterium levels). Additionally, gut dysbiosis was associated with peritonitis and enhanced inflammatory activity. In addition, some studies documented a beneficial effect on gut flora composition attributed to synbiotic and probiotic therapies. Large randomized clinical trials are required to investigate the impact of different microbiota modulation strategies on gut microflora composition and subsequent clinical outcomes. CONCLUSIONS: Patients with CKD had an altered gut microbiome profile, even at early disease stages. Different abundance at genera and species levels could be used in clinical models to discriminate between healthy individuals and patients with CKD. ESKD patients with an increased mortality risk could be identified through gut microbiota analysis. Modulation therapy studies are warranted.

Molecular Monitoring of Allogeneic Stem Cell Transplantation in Fanconi Anemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice in patients with Fanconi anemia (FA). The aim of our study is to evaluate the impact and benefits of allogenic matched donor HSCT in a case of a 12 year-old girl with FA, who displayed good clinical evolution following 2 months post-transplantation. METHODS: In the pre-transplant phase, reference blood samples from the donor and recipient were collected on EDTA. The DNA from blood samples was extracted using an automated Maxwell® 48 RSC instrument (Promega, USA) with the Maxwell® RSC Whole blood DNA kit (Promega, USA). For DNA quantification, the PowerQuant System kit (Promega, USA) was used with the ABI 7500 Real-time PCR system (Applied Biosystems, USA). The amplification of the short tandem repeat markers was performed using the 24plex Investigator QS kit (Qiagen, Germany) on a ProFlex PCR System. Furthermore, the PCR products were separated and detected on an ABI 3500 Genetic Analyzer (Applied Biosytems, USA). RESULTS: Thirty days post transplantation, a complete chimerism (CC) was achieved with a full replacement by do-nor derived hematopoietic cells. Sixty days post transplantation, the CC status was maintained with improvement of hematological findings. CONCLUSIONS: In FA, chimerism monitoring after HSCT provides useful information regarding engraftment or possibility of post-transplantation complications such as graft versus host disease.

Desquamative Gingivitis in the Context of Autoimmune Bullous Dermatoses and Lichen Planus-Challenges in the Diagnosis and Treatment.

Desquamative gingivitis (DG) is a clinical term that describes erythema, desquamation and erosions of the gingiva, of various etiologies. Although the clinical aspect is not specific for a certain disease, an accurate diagnosis of the underlying disorder is necessary because the disease course, prognosis and treatment vary according to the cause. DG may inflict significant oral discomfort, which is why patients typically present to the dentist for a first consultation, rendering it important for these specialists to be informed about this condition. Our paper aims to review the ethiopatogenesis and diagnostic approach of DG, focusing on the most common underlying disorders (autoimmune bullous dermatoses and lichen planus) and on the management of these patients. Potential etiological agents leading to an inflammatory immune response in the oral mucosa and DG appearance include genetic predisposition, metabolic, neuropsychiatric, infectious factors, medication, dental materials, graft-versus-host reaction and autoimmunity. A thorough anamnesis, a careful clinical examination, paraclinical explorations including histopathological exam and direct immunofluorescence are necessary to formulate an appropriate diagnosis. Proper and prompt management of these patients lead to a better prognosis and improved quality of life, and must include management in the dental office with sanitizing the oral cavity, instructing the patient for rigorous oral hygiene, periodic follow-up for bacterial plaque detection and removal, as well as topical and systemic therapy depending on the underlying disorder, based on treatment algorithms. A multidisciplinary approach for the diagnosis and follow-up of DG in the context of pemphigus vulgaris, bullous pemphigoid, cicatricial pemhigoid or lichen planus is necessary, including consultations with dermatologists, oral medicine specialists and dentists.