Secondary Sarcopenia and Spinal Cord Injury: Clinical Associations and Health Outcomes.

Background: Sarcopenia and spinal cord injury (SCI) often coexist, but little is known about the associations. This study aimed to assess the impact of SCI on muscle and bone mass and the correlations between the clinical characteristics of SCI patients and sarcopenia. Methods: A total of 136 patients with SCI admitted to rehabilitation hospital were included in this study. The type and severity of injury (AIS), level of spasticity (MAS), bone mineral density and Appendicular Lean Muscle Mass (ALM) were assessed. Sarcopenia was diagnosed according to EWGSOP2 cut-off points for ALM. Results: Subjects were divided into two groups: Group S-SCI (N = 66, sarcopenia group) and Group NS-SCI (N = 70, without sarcopenia). Mean ALM values in the two groups were 0.49 and 0.65, respectively. A total of 75% of women and 42.9% of men developed sarcopenia. The mean age was 35.8 years in the sarcopenic patients and 41.5 in the non-sarcopenia group. Over 55% of AIS Grades A and B cases, 69.7% of MAS level 0 cases and 51.6% of the patients with osteoporosis had sarcopenia. The mean number of comorbidities was 2.7 in the sarcopenia group. Conclusions: Gender, type of injury, presence of multiple comorbidities and age were directly associated with sarcopenia; meanwhile, surprisingly, spasticity level and the presence of immobilization osteoporosis were not.

Rehabilitation of Post-COVID-19 Musculoskeletal Sequelae in Geriatric Patients: A Case Series Study.

The musculoskeletal system is affected in over 40% of patients with Coronavirus disease 2019 (COVID-19). There is an increased need for post-acute rehabilitation after COVID-19, especially in elderly people with underlying health problems. The aim of this study was to evaluate the benefits of an early and goal-orientated rehabilitation program using combined approaches, robotic medical devices together with other rehabilitation techniques and therapies, in elderly people after acute COVID-19. Ninety-one patients (62.64 ± 14.21 years) previously diagnosed with severe SARS-CoV-2 infection were admitted to the Medical Rehabilitation Clinical Hospital Baile Felix, Romania, for medical rehabilitation, but only six patients (85.33 ± 3.07 years) met the inclusion criteria and participated in the study. The rehabilitation treatment was complex, performed over 4 weeks, and included combined approaches: exercise therapy, robotic gait training, occupational therapy, and massages. Activity and participation evaluation were performed using the Barthel Index and Functional Independence Measure for activities of daily living (ADLs). Assessments were performed at admission and discharge from the rehabilitation clinic. Lokomat patients' reports revealed that the patients had improved motor control (with one exception). The measurement of functional ability revealed an improvement in most cases. This study presents some of the first data on outcomes of COVID-19 patients' musculoskeletal rehabilitation in our country. Early complex medical rehabilitation improved functional independence and autonomy in ADLs in very old patients, post-COVID-19.

Genetic Counseling and Management: The First Study to Report NIPT Findings in a Romanian Population.

Background and Objectives: Non-invasive prenatal testing (NIPT) has been confirmed as the most accurate screening test for trisomies 21, 18, 13, sex chromosomes aneuploidies and several microdeletions. This study aimed to assess the accuracy of cell free DNA testing based on low-level whole-genome sequencing to screen for these chromosomal abnormalities and to evaluate the clinical performance of NIPT. Materials and Methods: 380 consecutive cases from a single genetic center, from Western Romania were included in this retrospective study. Cell-free nucleic acid extraction from maternal blood, DNA sequencing and analysis of sequenced regions were performed by BGI Hong Kong and Invitae USA to determine the risk of specific fetal chromosomal abnormalities. In high-risk cases the results were checked by direct analysis of fetal cells obtained by invasive methods: 6 chorionic villus sampling and 10 amniocenteses followed by combinations of QF-PCR, karyotyping and aCGH. Results: NIPT results indicated low risk in 95.76% of cases and high risk in 4.23%. Seven aneuploidies and one microdeletion were confirmed, the other results were found to be a false-positive. A gestational age of up to 22 weeks had no influence on fetal fraction. There were no significant differences in fetal fraction across the high and low risk groups. Conclusions: This is the first study in Romania to report the NIPT results. The confirmation rate was higher for autosomal aneuploidies compared to sex chromosome aneuploidies and microdeletions. All cases at risk for trisomy 21 were confirmed. Only one large fetal microdeletion detected by NIPT has been confirmed. False positive NIPT results, not confirmed by invasive methods, led to the decision to continue the pregnancy. The main limitation of the study is the small number of patients included. NIPT can be used as a screening method for all pregnancies, but in high-risk cases, an invasive confirmation test was performed.

Circulating Cell-Free Plasma DNA in Noninvasive Prenatal Paternity Testing with Short Tandem Repeats (STRs).

BACKGROUND: Paternity relationship can be established using STR markers in a minimally invasive manner during the prenatal period in the early weeks of pregnancy or in advanced pregnancy using circulating cell-free DNA (ccf DNA) drawn from the mother. The aim of our presentation is to demonstrate the advantages of ccf plasma DNA in establishing the paternity of an unborn child. Between mother and the alleged father (AF) of the fetus, an avuncular relationship as uncle-niece exists. METHODS: As biological samples, saliva was collected with buccal swabs from the mother and AF. For the fetus, we separated plasma from drawn blood from the mother, and further, we isolated ccf DNA from the mother's plasma sample. The DNA samples were quantified on a 7500 ABI Real-Time PCR using Investigator Quantiplex Pro Kit (Qiagen, Germany). Genotyping of the DNA samples was performed on a ProFlex PCR System (Thermo Scientific, USA) using the multiplex STR markers from Global Filer PCR Amplification Kit (Thermo Scientific, USA). Further, PCR products were run on capillary electrophoresis on an ABI 3500 Genetic Analyzer (Applied Biosystems, USA). RESULTS: The AF was confirmed as the biological father of the child, with a probability of paternity (PP) = 99.99999% and a cumulative paternity index (CPI) = 8.300 x 103. CONCLUSIONS: In the case of advanced pregnancies from sexual assaults or incestuous relationships, the use of ccf DNA to establish the genetic profile of the fetus represents an advantage for establishing the paternity relationship between the fetus and AF. The method proves its efficiency as it has the advantage of speed of probation through forensic genetic expertise.

De novo 8p21.3→ p23.3 Duplication With t(4;8)(q35;p21.3) Translocation Associated With Mental Retardation, Autism Spectrum Disorder, and Congenital Heart Defects: Case Report With Literature Review.

Duplications of chromosome 8p lead to rare genetic conditions characterized by variable phenotypes. 8p21 and 8p23 duplications were associated with mental retardation but only 8p23 duplication was associated with heart defects. 8p22→ p21.3 duplications were associated with an autism spectrum disorder in several cases. We present a rare case with a de novo duplication of the entire 8p21.3→ p23.3 region, documented by karyotype, FISH, and array CGH, with t(4;8)(q35;p21.3) translocation in a 7 years-old girl. She was referred for genetic counseling at the age of 20 months due to mild dysmorphic facial features, psychomotor retardation, and a noncyanotic heart defect. Another examination carried out at the age of 5 years, enabled the diagnosis of autism spectrum disorder and attention deficit hyperactivity disorder. Upon re-examination after two years she was diagnosed with autism spectrum disorder, attention deficit hyperactivity disorder, liminal intellect with cognitive disharmony, delay in psychomotor acquisitions, developmental language delay, an instrumental disorder, and motor coordination disorder. Cytogenetic analysis using GTG technique revealed the following karyotype: 46,XX,der(4),t(4;8)(q35;p21.3). The translocation of the duplicated 8pter region to the telomeric region 4q was confirmed by FISH analysis (DJ580L5 probe). Array CGH showed: arr[GRCh37]8p23.3p21.3(125733_22400607) × 3. It identified a terminal duplication, a 22.3 Mb copy number gain of chromosome 8p23.3-p21.3, between 125,733 and 22,400,607. In this case, there is a de novo duplication of a large chromosomal segment, which was translocated to chromosome 4q. Our report provides additional data regarding neuropsychiatric features in chromosome 8p duplication. The phenotypic consequences in our patient allow clinical-cytogenetic correlations and may also reveal candidate genes for the phenotypic features.

CHARGE syndrome associated with de novo (I1460Rfs*15) frameshift mutation of CHD7 gene in a patient with arteria lusoria and horseshoe kidney.

CHARGE syndrome is an autosomal dominant condition caused by mutations in the chromodomain helicase DNA binding protein 7 (CHD7) gene. The present study reported on the case of a 16-month-old female with plurimalformative syndrome, whose etiology was identified by clinical whole-exome sequencing (WES) analysis. Clinical and follow-up assessments identified multiple craniofacial dysmorphisms, congenital defects and functional symptoms, including dysphagia and Marcus Gunn jaw winking synkinesis. Trio-WES analysis was performed for the patient and their parents and the presence of CHARGE syndrome was further indicated using single-molecule real-time sequencing. A de novo pathogenic variant, c.4379_4380del (p.Ile1460Argfs*15), was identified in exon 19 of the CHD7 gene, which resulted in a premature translational stop signal. Trio-WES analysis was used for further investigation, indicating that neither of the patient's parents had the mutation and confirming its de novo nature. To the best of our knowledge, the case of the present study was the first reported case of CHARGE syndrome in Romania with congenital defects including an aberrant right subclavian artery and a horseshoe kidney. CHARGE syndrome was diagnosed in the patient based on the pathogenic mutation in the CHD7 gene. To the best of our knowledge, the present case report is the first to suggest that the CHD7 gene variant is associated with CHARGE syndrome.

Correlations between the Quality of Life Domains and Clinical Variables in Sarcopenic Osteoporotic Postmenopausal Women.

(1) Background: both sarcopenia and osteoporosis are major health problems in postmenopausal women. The aim of the study was to evaluate the quality of life (QoL) and the associated factors for sarcopenia in osteoporotic postmenopausal women, diagnosed according to EWGSOP2 criteria. (2) Methods: the study sample comprised 122 osteoporotic postmenopausal women with low hand grip strength and was divided into two groups: group 1 (probable sarcopenia) and group 2 (sarcopenia). QoL was assessed using the validated Romanian version of SarQol questionnaire. (3) Results: the D1, D4, D5, D7 and total SarQoL scores were significantly lower in women from group 2 compared to group 1. In group 2, women older than 70 years had significant lower values for D1, D3, D4, D6 and total SarQoL scores. Age, history of falls and the presence of confirmed and severe sarcopenia were predictors for overall QoL. (4) Conclusions: the frequency of sarcopenia was relatively high in our sample, with body mass index and history of falls as predictors for sarcopenia. Older osteoporotic postmenopausal women, with previous falls and an established sarcopenia diagnosis (low muscle strength and low muscle mass), were more likely to have a decreased quality of life.

Assessment of p53 and HER-2/neu genes status and protein products in oral squamous cell carcinomas.

Identification of the genes involved in tumor initiation and progression has led to development of new markers and generated targets for new drugs. This study aimed to evaluate p53 and HER-2/neu genes status of and their protein products in oral cancer patients. Tumor specimens from 116 cases diagnosed with oral squamous cell carcinoma were analyzed. P53 and HER-2/neu immunoreactivity were studied. FISH analysis was performed to elucidate p53 and HER-2/neu gene status. Male cases represented 84% of the group. The majority of cases were between 51-60 years and moderately differentiated oral carcinoma had an incidence of 58.6%. Thirty-four cases showed p53 overexpression, negative immunoreaction was observed in 16.37% of cases. 66.38% of cases had p53 deletion, with an increased rate observed in neoplasms of the tongue. Immunohistochemical analysis of HER-2/neu receptor protein revealed that 76.72% were negative, 5.17% had weak immunostaining, 14.65% had +2 score, the others had +3 score. 24.1% of cases were analyzed using FISH technique, of which 25% were without amplification, but with polysomy for chromosome 17. 18.1% of total cases were amplified, with the rate HER-2/neu:CEP17 higher than 2. Of the 77 cases with a single p53 allele, 20 associated HER-2/neu amplification, 31 had positive anti-HER-2/neu immunoreaction, but did not have HER-2/neu:CEP17 rate >2. There was a significant association between HER-2/neu amplification and deletion of a p53 allele. These results could justify more extensive research to assess p53 and HER-2/neu gene status as significant prognostic factors in oral cancers.

Imagistic and histopathologic concordances in degenerative lesions of intervertebral disks.

Lumbar disk lesions in 47 cases were initially diagnosed using MRI investigation, then, after surgery, biological and histopathological aspects of intervertebral disks were revealed. Pieces from intervertebral disks were used for electron microscopy studies in order to determine collagen in the components of the intervertebral disk. The aim of the present study was to highlight the correspondence between the MRI aspect in cases with clinically manifest lumbar hernia, staged according to MRI Modic classification, and the histopathological aspect in patients with surgical interventions on the intervertebral disks. 4/5 of the analyzed disks had advanced forms of degenerescence of the intervertebral disks: hyalinized disk cartilage ± intradiskal calcification or ossification zones, chronic inflammatory infiltrate at the disk cartilage level. Electron microscopy studies made on disk fragments obtained by discectomy revealed quantitative and qualitative changes of all types of collagen at the level of the three anatomical structures of the intervertebral disks, which correspond to the MRI changes.

Amplification of HER-2 gene in breast cancer: immunohistochemical and FISH assessment.

The invasive mammary cancer is the most frequent malignant tumor of women. Different inherited or acquired molecular genetic alterations have been identified in human breast cancers. A fraction of these cancers, as part of their development, undergoes gene amplification. Among the potential prognostic factors are included the biomarkers which measure or are associated with biological processes involved in tumor progression. Evaluation of HER-2 status is important in the management of patients with breast carcinoma, especially for the identification of those who are eligible for immunotherapy. The aim of our study was to evaluate HER-2 amplification status of human breast cancers by FISH and immunohistochemistry. From the total of 50 tumors included in the study, 17 (34%) presented different degrees of positivity; 33 (66%) did not express the oncoprotein HER-2. HER-2 gene and chromosome 17 status were tested in HER-2 2+ cases using FISH technique. FISH analysis may be useful to better evaluate HER-2 status in breast cancer in uncertain cases, where the immunohistochemistry score is 2+. HER-2 testing results have an important role in the clinical management of breast cancer patients. The identification of HER-2 positive tumors is certainly crucial in order to identify patient candidates for anti-HER-2 therapies.