TS Patients Research Articles

Metabolic Risk in Patients with a Diminished Ovarian Reserve and Premature Ovarian Insufficiency.

Objective: Diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) represent conditions of different severity, characterized by an earlier-than-expected decrease in ovarian activity. The present study aims to compare metabolic disturbances between women with DOR and patients with POI from a different origin. Materials and methods: A total of 226 women (28 healthy women; 77 individuals with DOR, and 121 patients with POI/36 with Turner syndrome [TS] and 85 with non-TS POI/) have been studied retrospectively. Data concerning anthropometric indices, and metabolic parameters were collected. Results: Patients with DOR, non-TS POI, and TS had increased blood pressure and liver enzymes, pronounced insulin resistance, and worse lipid profiles than controls (p < 0.008 for all). TS patients had significantly higher ASAT, GGT, and TSH levels compared to non-TS POI and DOR individuals. The prevalence of type 2 diabetes tended to be higher in TS women compared to other groups. The prevalence of previously diagnosed polycystic ovarian syndrome was lower in the non-TS POI patients than in the DOR patients (p = 0.005). Conclusions: patients with decreased ovarian function suffer from insulin resistance, abnormal lipid profile, and subtle hepatic disturbances, irrespective of the severity of the condition and the presence of chromosomal aberrations.

A small opening in the storm clouds: overview of the registry-based study on the management of thyroid storm.

Due to the high mortality rate of TS, effective guidance for its diagnosis and treatment is essential. The diagnostic criteria introduced by the JTA in 2012, along with the Burch-Wartofsky Point Scale, constitute valuable tools for the diagnosis of TS. In 2016, Guidelines on the management of TS were produced by the JTA and the JES. Recently, a prospective multicenter register-based study compared the prognosis and outcome of 110 new-onset TS patients with the results of previous comparable studies and evaluated the efficacy of the Guidelines. The study revealed higher APACHE II scores and significant correlations between lower BMI, post-resuscitation shock, and fever with outcomes and, overall, improved TS prognosis. Most patients in the study received methimazole and potassium iodide, the timely administration of which was linked to lower fatality rates. Adherence to treatment guidelines correlates with lower mortality rates, emphasizing the importance of experienced multidisciplinary teams in ICU settings and the necessity for periodic review of the guidelines to enhance therapeutic approaches and reduce mortality.

Bone mineral density: Comparison between women under hormone replacement therapy with Turner syndrome or idiopathic premature ovarian insufficiency

ContextTurner syndrome (TS) is characterized by short stature and premature ovarian insufficiency (POI). The main long-term complication of POI is osteoporosis, which can be prevented by hormone replacement therapy (HRT). ObjectiveThe objective of our study was to compare initial bone mineral density (BMD) and progression between TS and idiopathic POI patients under HRT. MethodsA single-center retrospective study was conducted between 1998 and 2018. All women had undergone at least two bone densitometry assessments at least 2 years apart. ResultsSixty-eight TS patients and 67 idiopathic POI patients were included. Mean age at initial assessment was 27 years (IQR, 21–35.5 years) in TS patients and 31.5 years (IQR, 23–37 years) in idiopathic POI patients (P=0.1). Lumbar and femoral neck BMD were lower in the TS group than in the idiopathic POI group (respectively 0.89g/cm2 versus 0.95g/cm2, P=0.03; 0.70g/cm2 versus 0.77g/cm2, P<0.0001). Mosaic karyotype was associated with better BMD in TS patients while history of growth hormone treatment had no impact on BMD. Over time, a significant gain in vertebral BMD was observed in TS patients versus a loss of BMD in idiopathic POI patients (P=0.0009). ConclusionTS patients had a lower BMD at baseline than idiopathic POI patients, at both spinal and femoral levels. Over time, on HRT, a significant gain in vertebral BMD was observed in patients with TS, compared with a loss of BMD in patients with idiopathic POI. We hypothesized that earlier initiation and longer duration of HRT played an important role in this finding. Long-term prospective follow-up to assess the incidence of fractures in TS would be useful.

P-004 Impact of short abstinence versus testicular sperm on sperm DNA fragmentation: a systematic review and meta-analysis of prospective studies

Abstract Study question Does testicular sperm result in lower sperm DNA fragmentation (SDF) compared to ejaculated sperm after short abstinence? Summary answer Testicular sperm exhibited significantly lower SDF than ejaculated sperm post-short abstinence. What is known already Optimal sperm DNA integrity is vital for fertilization and embryo health. Research shows testicular sperm typically exhibit lower SDF than ejaculated sperm with a standard abstinence period in the same individuals. Additionally, evidence indicates reducing abstinence to &amp;lt; 2 days may decrease SDF, presenting a simpler, more cost-effective strategy than surgical retrieval. Yet, no studies have directly compared the efficacy of shorter abstinence against testicular sperm extraction for lowering SDF. Study design, size, duration Meta-analysis of 16 randomized controlled and prospective observational studies including four on testicular sperm (TESA or TESE, called TS) and twelve on short abstinence ejaculation. The meta-analysis followed MOOSE guidelines, scrutinizing databases including Cochrane Library, Web of Science, Embase, MEDLINE(R) and PUMBED up to November 16, 2023. The analysis was conducted using RevMan. The observational studies’ methodological quality was assessed using the Newcastle-Ottawa Scale, and the overall evidence quality was evaluated following the GRADE criteria. Participants/materials, setting, methods To compare short ejaculation duration and TESA (are not directly compared in the literature) for SDF levels, we analyzed relevant data from studies of each method. We adjusted the participant numbers in the TS group by 1/3 and included each TS study 3 times, to perform a comparison against the short duration studies which were in a ratio of 1:3. This approach maintained an unaltered cumulative subject count for the meta-analysis of TS studies. Main results and the role of chance A total of 641 patients were included, comprising 120 and 521 patients with SDF measurements following TS and ejaculation after a short abstinence period, respectively. The studies had varied inclusion criteria, with not all patients having an initial elevated SDF. Some studies had incomplete details on age and other demographics. However, the mean± SD age of 93 TS patients was 38.15± 5.48 years vs. 37.7± 6.0 years of 444 short abstinence patients, demonstrating no significant difference (P = 0.544). Short abstinence durations ranged from 1 to 48 hours. Diverse DNA fragmentation tests were used: TUNEL assay in three testicular sperm studies, SCD assay in one, and in the short abstinence group, 4 used TUNEL and 6 used SCD assays, along with one each using SCSA and Halosperm. The mean± SD SDF was lower in the TS group than in the short abstinence group (Mean difference -9.48, 95%CI -12.45 to -6.52, P &amp;lt; 0.001, I2= 85%). Sensitivity analysis revealed that no single study significantly influenced the results. Employing the GRADE criteria, the initial assessment categorized the overall quality of evidence as low due to the observational nature of the acquired data. All studies were of medium to high quality. Limitations, reasons for caution Our meta-analysis, the first to compare two distinct methods for reducing SDF, while navigating through challenges of diverse study designs, variable patient characteristics, and differing DNA fragmentation tests. Despite these limitations, it marks a significant step in a field where direct, head-to-head comparisons have been absent, offering crucial insights. Wider implications of the findings This study suggests testicular sperm may be better than ejaculated sperm for improving SDF in infertility cases. Direct comparisons are needed, before deeming short abstinence less effective. Future research should directly compare reproductive outcomes using both methods. Trial registration number not applicable

Results of Turner Syndrome Treatment with Recombinant Human Growth Hormone in Albania

Background: There is no doubt that the use of rhGH in patients with TS brings satisfactory results regarding the improvement of height growth, realizing the improvement of the final adult height. This study aimed to evaluate the influence of the type/characteristic of the genetic anomaly on sex chromosome X on the outcome of treatment with rhGH among Albanian children diagnosed with TS. Methods and Results: This analytical-observational study was conducted at the Pediatric Endocrine Unit at University Hospital Centre Mother Teresa in Tirana, the only one of its kind treating TS pediatrics in Albania. Only TS patients who had attained near-adult height (NAH) by December 2023 were included in the analysis of this study. Near-adult height was obtained for 44(72.1%) patients. The mean age of starting treatment was 12.68±3.03 years. After a treatment duration of 3.60±2.26 years, the patients recovered 0.88±0.56 in height-for-age Z-score (HAZ), resulting in HAZ at the end of treatment of -2.73±0.87. They achieved their NAH of 144.56±6.53cm. Conclusion: Despite starting treatment late, our patients managed to gain 17.70±12.53cm in length. The progression of height improvement under rhGH treatment showed differences between chromosomal groups. The non-monosomy group had better results regarding NAH and HAZ at the treatment's end than the monosomy group.

White matter alterations predict outcomes of comprehensive behavioral intervention for tics in children with Tourette syndrome: A diffusion MRI study

AimTourette syndrome (TS) is a neurodevelopmental disorder that cause sudden uncontrolled rapid and repeated vocal sounds or movements called tics. Herein, diffusion magnetic resonance imaging (dMRI) connectometry was implemented to evaluate the white matter connectivity differences among TS patients. MethodsA total of 63 TS and 77 typically developed (TD) individuals were enrolled in the present study. dMRI connectometry was utilized to identify differences in connectivity patterns of white matter tracts in TS patients based on quantitative anisotropy (QA). QA was compared between TS and TD patients and correlated with severity scores such as Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tics Scale (PUTS). ResultsHigher white matter connectivity of corpus callosum and bilateral cingulum as well as lower connectivity of corticothalamic and corticostriatal pathways were evident in TS relative to TD. The baseline YGTSS motor, YGTSS total, and PUTS were negatively correlated with corticostriatal pathway, corticothalamic pathway, and bilateral cingulum integrity, respectively. The changes in tic severity scores were also positively correlated with alterations in the white matter integrity of these brain regions following behavioral therapy. ConclusionPatients with TS have several abnormalities in their white matter microstructure particularly in the cortico-striato-thalamo-cortical (CSTC) circuit, correlated with the severity of the disease. Besides, the post-behavioral therapy changes in the white matter integrity of these regions are demonstrated as response predictors.

Comparative Analysis of Three Posterior-Only Surgical Techniques for Isthmic L5-S1 Spondylolisthesis.

To compare adults with isthmic L5-S1 spondylolisthesis who were treated with three different surgical techniques: PS-only, TS, and transforaminal lumbar interbody fusion/posterior lumbar interbody fusion (TLIF/PLIF). This is a retrospective analysis of adults with L5-S1 isthmic spondylolisthesis (grade ≥2) who underwent primary all-posterior operations with pedicle screws. Patients were excluded if they had <1 year follow-up, anterior approaches, and trans-sacral fibular grafts. Patient demographics and surgical, radiographic, and clinical data were compared between groups based on the method of anterior column support: none (PS-only), TS, and TLIF/PLIF. Sixty patients met inclusion criteria (male patients 21, female patients 39, average age 47 ± 15 years, PS-only 16; TS 20; TLIF/PLIF 24). TS patients more commonly had high-grade slips and markedly greater slip percentage, lumbosacral kyphosis, and pelvic incidence. The three groups were similar for smoking status, visual analog scores/Oswestry Disability Index scores (VAS/ODI), surgical data, and average follow-up (40.1 ± 31.2 months). All groups had similarly notable improvements in Meyerding grade and lumbosacral angle. Slip reduction percentage was similar between groups. While there was a markedly higher overall complication rate for PS-only constructs, all groups had similarly notable improvements in ODI and VAS back scores. All-posterior techniques for L5-S1 isthmic spondylolisthesis resulted in excellent improvement in preoperative symptoms and HRQoL scores and similar radiographic alignment. Trans-sacral screws were more commonly used for high-grade slips. The use of anterior column support resulted in fewer overall complications than posterior-only instrumentation.

Optical coherence tomography detection of retinal neural loss in patients with tuberous sclerosis

PurposeTuberous Sclerosis (TS) is a rare, multisystem genetic disease caused by mutations in the TSC1 and TSC2 genes, leading to abnormalities in cell differentiation and proliferation. This study aimed to evaluate the neural integrity of individuals with TS by using Optical Coherence Tomography (OCT) to examine the peripapillary retinal nerve fiber layer (RNFL) thickness and the macular thickness in patients with TS and to compare with healthy controls.MethodsPeripapillary and macular OCT scans (Optopol Revo NX SD OCT) were performed on 41 eyes from 22 TS patients, divided into two groups based on the presence of retinal hamartomas, and compared to 20 eyes from a control group. The average peripapillary RNFL thickness was measured for each quadrant. The macular total thickness and ganglion cell layer (GCL) + inner plexiform layer (IPL) thickness were measured based on the Early Treatment Diabetic Retinopathy Study (ETDRS) map. All measurements were then compared between the groups and controls.ResultsThe TS group showed significantly reduced RNFL thickness and macular thickness when compared to the control group. Specifically, patients with retinal hamartomas exhibited an even more pronounced thinning of both RNFL and macular thickness.ConclusionsThese findings suggest that TS patients undergo significant changes in retinal neurodevelopment and experience axonal loss. This finding may have significant prognostic utility regarding central nervous system degeneration in TS, particularly among patients with retinal hamartomas. OCT may serve as a valuable tool for assessing axonal structural abnormalities in TS patients.Trial Registration Number: Not applicable.

Comparing clinical course and patients out comes in patients undergoing Open surgical Versus Thoracoscopic closure of the atrial and ventricular septal defects in children

The current study is aimed at evaluation of the impact of different surgical approaches while correcting congenital heart diseases (CHD). Clinical outcomes like; operative time, complications, hospital stay were evaluated in children undergoing surgical repair of atrial septal defect (ASD) and ventricular septal defect (VSD).&#x0D; Patients and methods: Between 2015 and 2019, a total of 111 patients surgically managed for CHD with male: female ratio of…. and mean age 10.42±3.24 years. Two surgical approaches: open either right anterolateral thoracotomy or sternotomy and thoracoscopic were used. The study conducted to determine the operative time, ICU stay, complications, recovery period and long term follow up of the patients in both the groups.&#x0D; Results: 67 patients with ASD and 44 patients with VSD underwent cardiac surgery. Mean operation time was significantly longer in TS patients in comparison with TT and ST groups. However, mean intensive care unit (ICU) stay and hospital stay were significantly shorter in TS group in comparison with TT and ST patients.&#x0D; Conclusion: TS approach in repair of congenital heart defects not only resulted of good cosmetic effect, but also reduces time in ICU and hospital stay in comparison with “classical” operational techniques. In this article we tried to show the whole results of research.&#x0D; Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 115-120

Blood glucose control in acute stroke patients under total energy restriction with different carbohydrate intake and SGLT2 inhibitors availability: a retrospective cohort study

Hyperglycemia in acute stroke patients worsens neurological outcomes. However, effective and safe management during the acute stage has not been established. Therefore, we aimed to compare the effect of medications and nutrition therapy on blood glucose control in three cohorts with different carbohydrate content and availability of sodium-glucose cotransporter 2 inhibitors (SGLT2is) to identify the current optimal treatment for acute-stage hyperglycemia. We retrospectively studied patients with acute stroke admitted to our hospital between 2011 and 2019. We divided the study period into three periods as follows: traditional (Td, 2011–2013), transition (Ts, 2013–2014), and novel (N, 2014–2019). To evaluate glucose-lowering efficacy and safety, we included conscious patients with glycated hemoglobin A1c ≥6.5%, blood glucose levels ≥11.1 mmol/L, normal renal function at admission, oral diet and medications, and fasting blood glucose (FBG) test on day 7. We performed total energy restriction (TER) in each period with different carbohydrate contents: 60% in Td, 40% in Ts, and N. The attending physicians chose glucose-lowering medications. SGLT2is were available in the N period only. Our target FBG was &lt;7 mmol/L by day 7. The 26, 22 and 36 patients were enrolled in the Td, Ts and N periods. The blood glucose levels significantly decreased by day 7 in all periods. The target FBG was achieved in 30.8% of Td patients, 31.8% of Ts patients, and 72.2% of N patients. The N period had the highest population of achieving the target FBG. The 40%-carbohydrate diet based on TER plus SGLT2is was the most effective way to lower blood glucose levels. The N period had the highest population of positive urine ketones. However, no symptomatic ketoacidosis occurred. A 40%-carbohydrate diet based on TER combined with SGLT2is might be a potentially effective and safe treatment for hyperglycemia in acute stroke-conscious patients.

Competing endogenous RNA network analysis of Turner syndrome patient-specific iPSC-derived cardiomyocytes reveals dysregulation of autosomal heart development genes by altered dosages of X-inactivation escaping non-coding RNAs

BackgroundA 45,X monosomy (Turner syndrome, TS) is the only chromosome haploinsufficiency compatible with life. Nevertheless, the surviving TS patients still suffer from increased morbidity and mortality, with around one-third of them subjecting to heart abnormalities. How loss of one X chromosome drive these conditions remains largely unknown.MethodsHere, we have generated cardiomyocytes (CMs) from wild-type and TS patient-specific induced pluripotent stem cells and profiled the mRNA, lncRNA and circRNA expression in these cells.ResultsWe observed lower beating frequencies and higher mitochondrial DNA copies per nucleus in TS-CMs. Moreover, we have identified a global transcriptome dysregulation of both coding and non-coding RNAs in TS-CMs. The differentially expressed mRNAs were enriched of heart development genes. Further competing endogenous RNA network analysis revealed putative regulatory circuit of autosomal genes relevant with mitochondrial respiratory chain and heart development, such as COQ10A, RARB and WNT2, mediated by X-inactivation escaping lnc/circRNAs, such as lnc-KDM5C-4:1, hsa_circ_0090421 and hsa_circ_0090392. The aberrant expressions of these genes in TS-CMs were verified by qPCR. Further knockdown of lnc-KDM5C-4:1 in wild-type CMs exhibited significantly reduced beating frequencies.ConclusionsOur study has revealed a genomewide ripple effect of X chromosome halpoinsufficiency at post-transcriptional level and provided insights into the molecular mechanisms underlying heart abnormalities in TS patients.

Penerapan Terapi Menghardik Halusinasi Terhadap Pasien Eks Psikotik dalam Rehabilitasi Sosial

Along with the rapid development, modernization and industrialization efforts, social changes and problems are growing. So that people who are unable to make adjustments, can experience mental turmoil, mental disorders and even mental disorders called psychotics. Therefore, this study aims to describe the application of hallucinatory rebuke therapy in the rehabilitation process of ex-psychotic patients at the Dosarso Shelter House, Kebumen. This research method uses a type of qualitative research with a case study approach. This study had 4 subjects, namely 2 ex-psychotic patients who were still experiencing hallucinations, 1 nurse and 1 administrator who worked at the Dosaraso Shelter in Kebumen. The results of this research show that rebuke therapy at the Dosaraso Shelter Home in Kebumen is carried out in groups and individually. The social rehabilitation service model provided by Dosaraso includes the Institutional Based Rehabilitation (IBR) service model. Then the type of psychotic experienced by TS patients is schizophrenic functional psychotic with auditory and visual hallucinations, while patient D is paranoid functional psychotic with auditory hallucinations. This rebuke therapy is carried out through several stages, namely starting from preparing the place, explaining the therapy, agreeing to the therapy, time contract, implementation, and finally asking the patient's feelings. This research can also help counselors in carrying out therapeutic steps for ex-psychotic patients so that it is very helpful in overcoming social problems in society.

Working towards risk stratification for ascending aortic dilatation in pediatric Turner syndrome patients: results of a longitudinal echocardiographical observation

This study aimed to longitudinally evaluate aortic root dimensions and elasticity in pediatric Turner syndrome (TS) in relation to known cardiac implications such as coarctation of the aorta (CoA) and bicuspid aortic valves (BAV) in order to create an improved risk profile for the presumed underlying vessel pathology in childhood. We report on the longitudinal findings of our pediatric TS outpatient clinic over a period of up to 7.6 years. Forty-nine TS patients (median age at baseline 9.7 ± 5.9 years, range 0–19.8) were followed-up for on average 2.9 ± 1.1 examinations and a median time of 3.4 ± 1.6 years. Aortic root (AoR) diameters and corresponding Z-scores were determined echocardiographically, and elasticity parameters as well as annual progression rates were calculated. At baseline, 16.3% of patients showed Z-scores > 2 at one or more levels of the AoR (35.7% of patients with BAV, odds ratio of 4.2). There was net progression to be noted at all measuring levels, leading to 28.6% of patients (50% of patients with BAV) exhibiting aortic dilatation at the end of follow-up. Progression correlated with the presence of BAV, non-mosaic monosomy, and age. A levelling-off of progression was seen with the onset of adolescence.Conclusions: Marked progression of aortic diameters leading to the development of dilatation can be observed in TS patients during childhood and stresses the importance of close surveillance during childhood. Main risk factors are BAV and complete monosomy 45X0. A beneficial influence of estrogen substitution can be suspected but needs further investigation.What is known:• Patients with Turner syndrome are at an increased risk for aortic dilatation and dissection.• The presence of BAV and complete monosomy 45X are additional risk factors.What is new:• Aortic dilatation can be detected in pediatric patients with Turner syndrome.• Relevant progression in childhood is possible in at-risk individuals and warrants close surveillance.

The quality of life and body image disturbances of Turner syndrome patients in Malaysia: a cross-sectional study

BackgroundTurner Syndrome (TS) is a rare sex chromosome abnormality occurring in 1 in 2500 female live births. To date, there is limited data on TS patients in Malaysia. This study aimed to investigate the quality of life (QoL) and body image disturbances among adult population with TS in comparison to age-matched controls in a tertiary hospital in Kuala Lumpur: Hospital Chancellor Tuanku Mukhriz, Universiti Kebangsaan Malaysia (HCTM, UKM).MethodsThis was a cross-sectional study carried out in HCTM, UKM, Kuala Lumpur. TS participants who attended clinic in HCTM, UKM and controls who were hospital staff members were recruited via purposive sampling. TS participants’ sociodemographic and clinical profiles were retrieved from medical records. Two validated, translated questionnaires; World Health Organization Quality of Life (WHOQOL-BREF) questionnaire and Body Image Disturbances Questionnaires (BIDQ) were completed by participants.ResultsA total of 34 TS patients were approached and 24 (70.5%) of them participated in this study. Their median (IQR) age was 24.0 (7.0) years and their responses were compared to 60 age-matched healthy females as controls [median age (IQR) = 24.0 (8.0) years]. The most common medical problem in TS participants was premature ovarian insufficiency (n = 23; 95.8%). There were no significant differences between TS and control groups’ median scores (overall QOL; 4.00 vs. 4.00, general health; 3.50 vs. 4.00, physical health; 14.86 vs. 15.43, psychological health; 14.67 vs. 14.00 and environment; 15.00 vs. 15.50) of the different WHOQOL-BREF domains. However, TS participants were found to score 13.33 against 16.00, lower than the control group (p < 0.05) in the social relationship domain. Comparatively, body image concerns among TS respondents were significantly higher in impairment in the mainly social areas of functioning (p < 0.05). ConclusionThe study demonstrated that the overall QoL of TS participants was good and almost similar to that of the controls. However, TS group had significantly lower scores for social domain and had greater concerns in social interactions, thus affecting their social life.

Importance of hospital and clinical factors in predicting of 30-day mortality in Takotsubo syndrome: data from the Swedish Coronary Angiography and Angioplasty Registry

Abstract Background Takotsubo syndrome (TS) is an acute heart failure condition that presents with symptoms similar to acute myocardial infarction. TS is often triggered by emotional or physical stress and is an important cause of morbidity and mortality but predictors of mortality in TS patients are not well understood. There is a need to identify high-risk patients and tailor treatment accordingly. Purpose The purpose of this study was to assess the importance of various clinical factors in predicting 30-day mortality in TS patients using a machine-learning algorithm capable of identifying complex relationships between variables. Methods We analyzed data from the nationwide Swedish Coronary Angiography and Angioplasty Registry for all TS patients between 2015-2022. Gradient boosting was used to assess the relative importance of variables in predicting 30-day mortality in TS patients. Results Of the 3,180 hospitalized TS patients, 76% were women. The average age was 68.3 ± 11.2 years. The crude all-cause mortality rate was 2.57% at 30 days. The most important variable in predicting 30-day mortality was the hospital where the patient was treated, with a relative importance of 35.5%. This was followed by the clinical presentation for angiography (21.1%), creatinine level (11.9%), Killip class (8.9%), and age at angioplasty (6.5%). Other less important factors included weight, height, and certain medical conditions such as hyperlipidemia, smoking status, and hypertension. Gender and previous stroke history had a low impact on 30-day mortality in TS patients. Conclusions The treating hospital was the most important factor in predicting 30-day mortality in TS. Since the level of evidence for recommended treatments of TS is low, our findings highlight the importance of conducting randomized studies in this patient group to improve care.

Abstract 14415: Aortic Strain and Stiffness in Patients With Turner and Marfan Syndrome: Non-Invasive Phenotyping of Aortic Biomechanical Properties

Introduction: Turner and Marfan Syndromes (TS and MFS) are hereditary connective tissue disorders with increased risk of aortic aneurysm and rates of dissection. Prior studies suggest that TS and MFS have increased aortic stiffness when compared to healthy controls but comparative phenotyping of central aortic stiffness between the two syndromes has not yet been performed. Hypothesis: Non-invasively derived aortic biomechanical properties will differ between MFS and TS patients. Methods: Patients underwent cardiac MRI to evaluate central aortic strain and stiffness. Circumferential strain was evaluated using relative area change (RAC) for both the ascending and descending aorta and longitudinal aortic strain (LAS) was measured in the ascending aorta. Stiffness was evaluated using pulse wave velocity (PWV) and by wave-intensity analysis derived backward compression wave (BCW) ratio measuring stiffness of arch and abdominal vessels. Results: Patients with TS (N=53, mean age: 17.2±5.4) and MFS (N = 22, mean age: 17.8±6.2) had similar ascending aortic size and z-score. When compared to TS, MFS patients had reduced RAC in both ascending (33 vs 16%, P &lt; 0.05) and descending aorta (24 vs 14%, P &lt; 0.01) (Figure). PWV was increased in MFS in both ascending (4.0 vs 3.0 m/s, P &lt; 0.01) and descending aorta (3.8 vs 4.7 m/s, P &lt; 0.01). LAC was reduced in MFS patients as well (14 vs 8%, P &lt; 0.01). Lastly, MFS had increased BCW ratio for arch vessel stiffness (0.11 vs 0.26, P &lt; 0.01) with no difference in abdominal vessels (0.35 vs 0.36, P = NS). Conclusion: In contrast to TS, MFS patients have comparably increased stiffness and reduced compliance throughout the central aorta including aortic arch vessels. These differences are in parallel with clinical observations describing higher rate of aortic events throughout the entire aorta in patients with MFS. Our results might also be critical given the increasingly dominant role of biomechanical indices in the risk assessment for aortic events.

Impact of surgeon specialty on clinical outcomes following esophagectomy for cancer

BackgroundThe impact of surgeon and hospital operative volume on esophagectomy outcomes is well-described; however, studies examining the influence of surgeon specialty remain limited. Therefore, we evaluated the impact of surgeon specialty on short-term outcomes following esophagectomy for cancer.MethodsThe 2016–2019 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) was queried to identify all patients undergoing esophagectomy for esophageal cancer. Surgeon specialty was categorized as general (GS) or thoracic (TS). Entropy balancing was used to generate sample weights that adjust for baseline differences between GS and TS patients. Weights were subsequently applied to multivariable linear and logistic regressions, which were used to evaluate the independent association of surgeon specialty with 30-day mortality, complications, and postoperative length of stay.ResultsOf 2657 esophagectomies included for analysis, 54.1% were performed by TS. Both groups had similar distributions of age, sex, and body mass index. TS patients more frequently underwent transthoracic esophagectomy, while GS patients more commonly received minimally invasive surgery. After adjustment, surgeon specialty was not associated with altered odds of 30-day mortality (adjusted odds ratio [AOR] 1.10 p = 0.73) or anastomotic leak (AOR 0.87, p = 0.33). However, TS patients exhibited a 40-min reduction in operative duration and faced greater odds of perioperative transfusion, relative to GS.ConclusionAmong ACS NSQIP participating centers, surgeon specialty influenced operative duration and blood product utilization, but not mortality and anastomotic leak. Our results support the relative safety of esophagectomy performed by select GS and TS.

PREVELANCE OF CARBAPENEMASE PRODUCING ORGANISMS AND MOLECULAR RAPID DETECTION OF DIFFERENT GENES FROM VARIOUS CLINICAL ISOLATES IN PATIENTS ADMITTED AT TERTIARY CARE HOSPITALS OF VADODARA

Introduction- Carbapenemase-producing organisms (CPO) have been identied as an urgent healthcare threat. The spread of carbapenemase-producing Enterobacterales (CPE) is a global health problem of great concern. Rapid detection of carbapenemase-producing organisms is clinically desirable for hospital infection control and antibiotic stewardship. Recently, an on-demand polymerase chain reaction (PCR) assay, namely, the Xpert CarbaR assay, that requires less than an hour of turnaround time, had been developed for CPO detection in clinical samples to identify and guide infection control programs to contain the spread of CPO within a hospital. Objective- Carba-R assay is a qualitative multiplex real-time PCR method that qualitatively detects and differentiates ve common carbapenemase genes blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP) directly from clinical samples or puried colonies within approximately 1 hour. This benets hospitals and patients by facilitating timely Infection Prevention &amp; Control measures, thereby reducing risk of exposure, transmission and bed-days lost. Materials &amp; Methods- In this study, the Xpert Carba-R assay was evaluated for detection of the ve carbapenemase genes (blaKPC, blaNDM, blaIMP, blaOXA-48, and blaVIM) in total of 40 non duplicate various clinical samples of admitted patients in tertiary care hospitals of Vadodara. Result- We performed Carba-R on 40 isolates: 18 blood samples, 06 urine, 05 rectal swabs, 03 Endotracheal secretion, 03 Pus, 02 wound discharge, 01 Bronchoalveolar lavage uid, 01 sputum, and 01 ERCP stent isolates. 36/40 (90%) isolates had one or more carbapenemase genes. They were as follows: 19/40 (47.5%) both OXA48 and NDM , 12/40 (30%) NDM and 05/40(12.5%) OXA-48. There were 04/40 (10 %) isolates which were Carbapenem resistant on disc diffusion &amp; VITEK but none of the resistant genes were detected possibly due to other resistant mechanism like efux pump and porin channels. Klebsiella pneumoniae was the most common isolate with CR, 34/40 (85%). The most frequent genes encountered in Klebsiella pneumoniae were both OXA48 and NDM, 19/34 (55.88%), NDM 08/34 (23.53%) followed by OXA 48, 05/34 (14.71%) and Out of 34 Klebsiella isolates, 02 isolates failed to detect any of these ve carbapenemase genes. Conclusion- Xpert Carba-R assay provides good reliable results for detection and differentiation of ve carbapenemase genes in clinical isolates. Compared to bacterial culture followed by PCR identication of resistance genes from colonies, the Carba-R assay reduced turnaround time from 48 to 72 hours to less than 1 hour. Carbapenemase genes were detected by the Carba-R assay in Klebsiella pneumoniae (34/40), Escherichia coli (5/40), Acinetobacter spp (1/40). The Carba-R assay detected 19 both OXA48 and NDM (47.5%), 12 blaNDM (30% and 05 blaOXA-48 (12.5%) genes. Laboratory detection of these genes may help improve patient outcomes by tailoring therapy. This study was conducted for understanding the molecular epidemiology of Carbapenemase producing Enterobacteriaceae in a tertiary care hospital. The combined use of the Xpert Carba-R assay and culture produces rapid and reliable results for the active surveillance of CPO in patients

Symptoms compatible with long COVID in an Italian pediatric cohort of Tourette patients with and without SARS‑CoV‑2 infection: a short-term follow-up assessment

BackgroundTourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 0.3–1% of the population. During the pandemic caused by SARS-CoV-2 infection, the impact on the mental health of children and adolescents was very important. The persistence of symptoms in the post-acute phase of the disease has been termed Long COVID. The neuropsychiatric symptoms seem to be the most common impairment in children and adolescents with long COVID.ObjectivesConsidering the impact of pandemic on mental health, in this study we analyzed the long-term effects of SARS-CoV-2 infection in children and adolescents affected by TS.MethodsWe conducted an online questionnaire covering socio-demographic and clinical data among 158 patients affected by TS or chronic tic disorders (CTD), of which 78 participants reported a positive SARS-CoV-2 infection. Data were collected to investigate tic severity and both the comorbidities, as well as lockdown-related changes to daily life activities and, in case of infection of SARS-CoV-2, possible symptoms of acute infection and long COVID. Markers of systemic inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, iron, electrolytes, white blood cell counts, platelet cell counts levels, markers of liver, kidney and thyroid function were analyzed. First, all patients were screened with the Schedule for affective disorders and Schizophrenia for School age children—present and lifetime (Kiddie-SADS-PL) to rule out primary psychiatric disorders considered as criteria of exclusion. Then, all patients were clinically assessed at baseline (T0), and after three months (T1) through the administration of Yale Global Tic Severity Rating Scale (YGTSS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and Child Behavior Checklist (CBCL).ResultsAmong the cohort of TS patients that contracted SARS-CoV-2 infection, 84.6% (n = 66) experienced any acute symptoms, and long COVID symptoms occurred in 38.5% (n = 30). A worsening of clinical symptoms of tics and eventually associated comorbidities occurred in 34.6% (n = 27) of TS patients that contracted SARS-CoV-2 infection. TS patients with or without SARS-CoV-2 infection showed an increase in the severity of tics and also behavioral, depressive and anxious symptoms. Instead, this increase was more evident in patients who contracted the infection than in patients who did not contract it.ConclusionsSARS-CoV-2 infection may have a role in the increase of tics and associated comorbidities in TS patients. Despite of these preliminary results, further investigations are necessary to improve knowledge about the acute and long-term impact of SARS-CoV-2 in TS patients.

Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model

To study the impact of aneuploid granulosa and stromal cells on folliculogenesis of small ovarian follicles from mosaic Turner syndrome patients using a murine xenograft model. Laboratory study SUBJECTS: Ovarian cortical tissue was obtained by laparoscopic surgery from 18 mosaic TS patients (aged 5-19 years) and 13 controls (aged 5-18 years). Part of each tissue fragment was used to karyotype ovarian cells in non-grafted tissue by fluorescence in situ hybridization. The remaining tissue was xenografted to severe combined immunodeficient mice for 5 months. Grafted tissue was analyzed for aneuploidy, and follicle density and morphology were determined. Expression of proliferating cell nuclear antigen and anti-Müllerian hormone were investigated by immunohistochemistry. The impact of aneuploid granulosa and stromal cells on folliculogenesis. Fluorescence in situ hybridization of ovarian tissue before grafting was performed to determine the level of aneuploidy in stromal cells, and oocytes and granulosa of small follicles. After xenografting the level of aneuploidy of the newly formed layers of granulosa cells was again determined in secondary and antral follicles. Follicle density in ovarian tissue from Turner syndrome patients was significantly lower than in controls before grafting. Fluorescence in situ hybridization analysis confirmed that 101/104 oocytes from non-grafted tissue of Turner syndrome patients showed normal X chromosome content, while granulosa and stromal cells were mainly 45,X. Fragments from 12 Turner syndrome patients contained follicles at all stages after xenografting, including secondary and antral follicles. Follicle density in Turner syndrome patients and controls decreased significantly after grafting. Moreover, a shift from high to low proportions of 45,X granulosa cells was observed during folliculogenesis. Expression of PCNA in follicles from TS patients increased significantly during grafting. Secretion of AMH was impaired before grafting in peri-/postpubertal TS girls, but recovered after grafting. Our study showed that small follicles from mosaic Turner syndrome patients undergo folliculogenesis, despite the presence of aneuploid granulosa and stromal cells. Ovarian tissue cryopreservation could therefore be a valid option to preserve fertility in young mosaic Turner syndrome patients if sufficient numbers of follicles are present, thus preferably before the age of 12.