Whole Group Of Patients Research Articles

Use of belimumab in treating patients with systemic lupus erythematosus: a single-center, real-world retrospective study

ObjectiveTo investigate the efficacy and safety of belimumab in the treatment of systemic lupus erythematosus (SLE) in a real-world setting and provide a valuable reference for clinical treatment.MethodsIn this retrospective study, 101 patients with SLE who came to our hospital from March 2020 to September 2022, 56 of whom with lupus nephritis (LN), were selected. All patients received belimumab in combination with standard of care(SoC)therapy regimen for more than 52 weeks and their clinical/laboratory data, assessment of disease activity, glucocorticoids dosage and occurrence of adverse events were recorded. Lupus Low Disease Activity State (LLDAS) and DORIS remission as a primary goal in the treatment of SLE. The groups were classified according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K): SLEDAI-2 K < 6 was categorized as the mild group (mild activity) and SLEDAI-2 K ≥ 6 was categorized as the active group (moderate-severe activity). The disease of the two groups mentioned above were assessed using the SELENA-SLEDAI Flare Index (SFI) and the SLE Responder Index-4 (SRI-4), respectively. Furthermore, we used complete remission (CR) and partial remission (PR) in the kidney as the standard for efficacy evaluation for LN patients.ResultsAfter 52 weeks of treatment with belimumab, patients’ complement levels increased significantly (p < 0.05); Other indicators such as 24-hour urine protein quantification and daily glucocorticoids dose decreased compared to pretreatment (p < 0.05). At 52 weeks, (i) after evaluation, the whole group of patients showed significant improvement in their condition; (ii) 55.4% of patients achieved LLDAS and 23.8% achieved DORIS remission; (iii) 73.2% of patients with LN achieved CR, 16.1% achieved PR. Adverse reactions were observed in 15 patients (14.9%), all of which normalized after symptomatic treatment.ConclusionsIn general, during treatment with belimumab, immunological and biochemical indices improved in SLE patients, urinary protein levels were reduced in LN patients, and the rate of renal function remission was effectively increased; At the same time, the use of belimumab is associated with a low frequency of side effects, good overall tolerability and a favorable safety profile.

Reperfusion therapy and risk of post-stroke delirium

ABSTRACT Objectives Delirium is a common and serious post-stroke complication. Early reperfusion by ameliorating brain damage could potentially prevent delirium after ischemic stroke, but the impact of this therapy on delirium remains unclear. We aimed to explore the association between reperfusion therapy (RT) and post-stroke delirium. Methods We retrospectively analyzed data from the PRospective Observational POLIsh Study on post-stroke delirium. Symptoms of delirium were examined during the first 7 days after admission and a diagnosis of delirium was made using Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. We used logistic regression to examine the association between RT and delirium. Results We included 301 acute stroke patients (median age: 77; median NIHSS: 14; 55.1% female). In the whole group of patients, RT was associated with a lower odds of delirium (34.2% vs 44.8%; adjusted OR: 0.56, 95% CI: 0.32–0.96, p = 0.035). There was a significant interaction between RT and pre-stroke cognitive status. As a result, RT was associated with a lower odds of delirium in patients without premorbid cognitive decline (28.8% vs 48.2%; adjusted OR: 0.34, 95% CI: 0.17–0.66, p = 0.002) and a higher odds of delirium in patients with pre-stroke cognitive decline (72.7% vs 41.0%; adjusted OR: 3.55, 95% CI: 1.03–12.20, p = 0.040). Discussion The association between RT and delirium is modified by pre-stroke cognitive status. In patients without cognitive decline, RT is associated with a lower likelihood of delirium. Delirium should be considered as a relevant outcome in future controlled trials.

Smoking-Dependent Association of Serum Brain-Derived Neurotrophic Factor with Pulmonary Function Parameters in Chronic Obstructive Pulmonary Disease.

Background and Objectives: One of the members of the neurotrophin (NT) family is the brain-derived neurotrophic factor (BDNF). In addition to its role in the nerve system, it has been found to play a role in lung health and diseases. Materials and Methods: The serum concentrations of BDNF were assessed in 57 patients with COPD and in 19 control individuals and the possible associations of BDNF with the spirometric indexes and disease stages were explored. Results: We did not find a significant difference between the serum concentrations of BDNF of patients and controls (p = 0.521). A significant negative correlation of the serum BDNF levels with the age of the patients (Rho = -0.279, p = 0.036) was observed. In addition, a borderline negative correlation with the age of disease onset (Rho= -0.244, p = 0.063) was also found. When analyzing these correlations in different genders, we found stronger statistical significance in male patients (Rho = -0.398, p = 0.009; and Rho = -0.419, p = 0.006), while no such significance was found in females (p = 0.574 and p = 0.342). The analyses of the possible relations of serum BDNF concentration with the spirometric parameters in the whole group of patients did not reveal any significance (p = 0.231 for FEV1%pr. and p = 0.271 for FEV1/FVC%). However, when the patients were dichotomized on the basis of smoking habits, we obtained a strong positive correlation between BDNF and FEV1%pr. (Rho = 0.501, p = 0.048) in non-smokers, but strong negative correlations with FEV1%pr. (Rho = -0.468, p = 0.003) and with FEV1/FVC% (Rho = -0.331, p = 0.040) in ex/current smokers. Non-smokers with moderate disease (GOLD II) had higher BDNF serum concentrations than patients with GOLD stage III/IV (p = 0.031). In ex/current smokers, there was an opposite association (p = 0.045). Conclusions: The results of our study suggest that the expression and secretion of BDNF are changed in COPD, but its effects and functions may differ according to the smoking history of the patients.

LEVELS OF MICRO RNA-21-3R IN THE BLOOD OF HYPERTENSIVE PATIENTS WITH NORMAL BODY WEIGHT AND WITH ABDOMINAL OBESITY

Objective: The combination of arterial hypertension (AH) with abdominal obesity (AO) significantly increases the severity of hypertension and accelerates the development of hypertension-mediated organ damage, in particular, left ventricular hypertrophy (LVH). MicroRNAs are small non-coding RNA molecules that are involved in the regulation of post-transcriptional gene expression. A number of experimental studies have revealed the antihypertensive, antihypertrophic and antifibrosing properties of microRNA-21-3p. The goal is to study the plasma levels of microRNA-21-3p in hypertensive patients with normal body weight (NBW) and with abdominal obesity (AO). Design and method: 27 patients (16 men) with stage 2-3 hypertension (13 with NBW and 14 with stage II AO) aged from 42 to 60 years were examined. The control group consisted of 12 practically healthy individuals. All patients underwent general clinical laboratory and instrumental examination. Circulating plasma microRNA-133a levels were obtained by polymerase chain reaction using the CFX96 Touch System, “TaqMan microRNA Assay” and “TaqMan® Universal PCR Master Mix” reagent kits. Results: A significant decrease in the levels of micoRNA-21-3p in the blood plasma was established in the whole group of patients with hypertension (with NBW and with AO) (1.43±0.08), p&lt;0.05) in comparison with practically healthy individuals (3.24 ±0.07). At the same time, the levels of this miRNA in the blood plasma of patients with hypertension and AO (1.13±0.06) were significantly lower (p&lt;0.05) than in patients with hypertension and NBW (1.67±0.07). A correlation analysis revealed negative correlations between the levels of micoRNA-21-3p in the blood plasma and the levels of “office” systolic blood pressure (R=-0.44; p=0.04), as well as the left ventricular myocardial mass index (LVMMI) (R= -0.38; p=0.03) in the whole group of patients with AH (with NBW and AO). Conclusions: The results of this study may indicate the presence of a significant deficiency in the production of mircRNA-21-3p in patients with hypertension, especially when it is combined with AO, as well as the involvement of this miRNA in the mechanisms of progression of hypertension and the development of LVH.

Postoperative Stability in Displaced Ankle Fractures With Concomitant Ligamentous Injuries

Ankle instability, which can be attributed to either the deltoid or lateral ligamentous complex, may be both a cause and a consequence of ankle fractures. This study aimed to assess postoperative ankle instability in patients with displaced ankle fractures. A total of 54 patients with displaced ankle fractures were included. Malleolar fractures were surgically reduced and fixated, and if necessary, the syndesmosis was stabilized. Concomitant deltoid injuries were left unrepaired. Ankle stress radiographs were taken approximately 25.4 months after surgery, with a standard deviation of 20.5 months. Radiographic measurements included the tibiotalar tilt angle (TT) on varus stress view, anterior translation of the talus (AT) on the anterior drawer view, and the medial clear space (MC) and tibiotalar tilt angle on the valgus stress view. These measurements were compared between the injured and the noninjured contralateral ankle for all patients as well as in a subgroup of 19 patients with concomitant deltoid and syndesmosis injuries. There were no significant differences in Varus TT (p = .675, p = .394), AT (p = .516, p = .967), Valgus MC (p = .190, p = 0.498), and Valgus TT (p = .173, p = .442) between the injured and noninjured ankles in the whole group of patients as well as in the subgroup of patients with concomitant deltoid and syndesmosis injuries. Patients with displaced ankle fractures exhibited radiographically stable ankles postoperatively. Syndesmosis fixation without deltoid ligament repair is a viable treatment option for achieving ankle stability postoperatively in fractures with both ligament injuries.

Subgroups of patients with late onset schizophrenia-like psychoses revealed by the analysis of glutathione-dependent enzymes and inflammation markers

IntroductionWhile chronic inflammation and enhanced imbalance of pro- and antioxidant, including glutathione-dependent, systems contribute substantially to pathogenesis of mental disorders in old age, extent of oxidative stress and degree of inflammatory processes severity are varying among patients with late onset schizophrenia.ObjectivesRevealing various phenotypes in patients with late onset schizophrenia basing on measurement of activity levels for blood glutathione-dependent enzymes and inflammation markers and analysis of their links with clinical features of the patients.MethodsOf 59 studied women patients 34 were with late onset (after 40 years) and 25 with very late onset (after 60 years) schizophrenia or schizophrenia-like psychoses (F20; F22.8; F25; F23; F06.2 by ICD-10). 34 mentally healthy women elder than 50 years comprised controls. Glutathione reductase (GR), glutathione-S-transferase (GST), neutrophil elastase (NE), and α1-roteinase inhibitor (α1-PI) activities were measured in blood. PANSS, CDSS and CGI-S were used to assess the severity of psychotic symptoms, depression and treatment effectiveness.ResultsIn the whole group of patients, GR was lower (p&lt;0.05), and α1-PI was higher (p&lt;0.0001) than in control group. Clustering the patients by their biochemical and immunological signs revealed two clusters (C1, n=34, and C2, n=25) significantly differing by GST (p&lt;0.0001), NE (p&lt;0.0001), and α1-PI (p&lt;0.001) activities. As compared with controls, GST and α1-PI were higher (p&lt;0.05 and p&lt;0.0001), and NE was lower (p&lt;0.05) in C1. As compared with controls, GR activity was lower (p&lt;0.05), NE activity was higher (p&lt;0.001), and α1-PI activity was much higher (p&lt;0.001) in C2. Patients of C1 and C2 did not differ in age, diagnosis, severity of the disease, but differed in clinical features of the course of the disease: significantly more patients with very late onset schizophrenia (76%) were met in C1 (χ2=13.41, p&lt;0.001). Also, different clinical-biological correlations were found in these clusters. Particularly, negative correlations of baseline NE activity with PANSS general psychopathology subscale scores (R=-0.39, p&lt;0.05) and with total PANSS scores (R=-0.39, p&lt;0.05) were found in C1. Positive correlation of GST activity with PANSS positive subscale score was found in C2 (R=0.43, p&lt;0.05).ConclusionsThe revealed clusters differ in the extent of the glutathione antioxidant system impairment and in levels of the immune response markers. The revealing of the patient subgroups on the basis of biological markers reflecting impairments in metabolic and immune systems can represent interest in the search for individual treatment approaches.Disclosure of InterestNone Declared

Small and large fiber neuropathy in adults with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder that affects multiple organs. In this study, we investigated symptoms of pain and presence of small and large fiber neuropathy in the juvenile and adult form of DM1. Twenty genetically verified DM1 patients were included. Pain was assessed, and neurological examination and investigations of the peripheral nervous system by quantification of small nerve fibers in skin biopsy, quantitative sensory testing and nerve conduction studies were performed. Results from skin biopsies were compared to healthy controls. Seventeen patients reported chronic pain. Large and/or small fiber abnormalities were present in 50% of the patients. The intraepidermal nerve fiber density was significantly lower in the whole group of patients compared to healthy controls. Small-fiber neuropathy might be an important cause of pain in DM1.

The Value of Coronary Computed Tomography Angiography in Patients with a High Calcium Score.

We aimed to assess the agreement between coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) to determine whether patients with a high coronary artery calcium score (CS) would benefit from CCTA. This cross-sectional study was conducted on patients suspected of having coronary artery disease. The patients underwent calcium scoring. The total CS and the number of calcified foci were determined. The calcium score index (CSI) was defined, and coronary arteries were evaluated by CCTA. ICA was performed, and reports of ICA were extracted. All the abovementioned variables were compared. For data analysis, the κ coefficient and the ROC curve were used. The study population consisted of 195 patients: 124 men (63.6%) and 71 women (36.4%). The median (IQR) value of CS was 529 (229-1042), ranging from 17 to 4717. In all 195 patients, the concordance between the final impression of CCTA and ICA was 90.2%, while the number and type of involved territories were similar at 57.9%. The highest agreement was seen in the left main and right coronary arteries, whereas the lowest agreement was detected in the left anterior descending and the left circumflex artery. The patients were categorized into different CS groups, and in those with a high CS (>1000), the agreement between CCTA and ICA concerning final impression and involved territories was similar to the whole group of patients. CCTA in patients with a high CS, even exceeding 1000, remains beneficial as the noninvasive available method.

Evaluation of Imaging Findings in Patients with Pretransplant and Posttransplant Tertiary Hyperparathyroidism.

Tertiary hyperparathyroidism, characterized by autonomous overproduction of parathyroid hormone, can be seen in patients with long-standing secondary hyperparathyroidism (pretransplant) or after renal transplant (posttransplant). Parathyroid scintigraphy and ultrasonography are the most commonly used imaging procedures for the preoperative localization of abnormal parathyroid glands. We aimed to evaluate imaging findings in pretransplant and posttransplant tertiary hyperparathyroidism. This study included 32 patients with pretransplant tertiary hyperparathyroidism and 20 patients with posttransplant tertiary hyperparathyroidism. On parathyroid scintigraphy with technetium-99m sestamibi, early-phase and latephase images were acquired. Images were evaluated for the presence and the number of active foci and the degree of uptake on the late-phase image. The existence of an autonomous gland was based on latephase retention and was scored from 0 to 2 (retention score). On ultrasonography, the criteria threshold for autonomy was the maximum length of the largest gland ≥10 mm (ultrasonography score). On parathyroid scintigraphy, the most commonly observed pattern in the pretransplant group was positivity in ≥3 glands, and in the posttransplant group the most commonly observed pattern was positivity in 1 to 2 glands. In pretransplant and posttransplant groups, the criteria threshold for the presence of an autonomous parathyroid gland on parathyroid scintigraphy (grade 2 retention) was met in 26 (81%) and 9 (45%) patients and on ultrasonography in 25 (78%) and 10 (50%) patients, respectively. In the whole group of patients (n = 52), correlation existed between ultrasonography score and retention score. Glandular weight was correlated with both retention score and ultrasonography score. Higher numbers of detectable glands and the presence of parathyroid autonomy were more common in the pretransplant group. This might be explained by parathyroid gland involution after transplant. The results may also suggest that factors other than autonomy are responsible for posttransplant tertiary hyperparathyroidism.

In vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in frontotemporal degeneration and corticobasal syndrome.

AbstractBackgroundNeuropathological studies have shown alterations in both locus coeruleus (LC) and basal forebrain in frontotemporal degeneration (FTD) and corticobasal syndrome (CBS) particularly in progressive supranuclear palsy (PSP). We aimed to investigate in vivo the LC and nucleus basalis of Meynert (NBM) integrity in patients with FTD and CBS.MethodWe compared the LC signal intensity (LC‐I), which reflects the LC integrity, and the NBM volume on 3T MRI in i) FTD patients (n = 17) ii) CBS patients (n = 8;) iii) prodromal/mild AD (n = 34) and iv) amyloid‐negative controls (n = 15). PiB‐PET and/or AD CSF biomarkers were negative in all FTD and CBS patients, and positive in all AD patients. All subjects underwent a complete neuropsychological assessment and 3T brain MRI performed on the same scan. The four groups were age‐matched. The MMSE score did not differ significantly between the 3 groups of patients.ResultCompared to controls, LC‐I and NBM volume were significantly decreased in FTD (p = 0.05 and 0.00015, respectively) and AD patients (p = 0.0005 and 0.002, respectively). LC‐I and NBM volume were also decreased in CBS in comparison with controls but the difference was not statistically significant. In addition, we found no statistically significant difference in LC‐I and NBM volume between the three groups of patients. We observed no correlation between LC‐I or NBM volume and amyloid load, either when considering the whole group of patients or AD and FTD/CBS patients separately.ConclusionOur results are in line with neuropathological data and suggest that both cholinergic and noradrenergic systems are altered in AD and FTD. Post mortem data have suggested that, in FTD, both structures were more impaired in tau than in TDP‐43 proteinopathy, which cannot be explored in our study. In CBS, our results are less clear‐cut, probably due to the small sample size. Taken together, our data support the pathophysiological model in which both LC and NBM play a critical role not only in AD but also in other diseases and proteinopathies like FTD.

Is myocardial fibrosis appropriately assessed by 2D strain derived integrated backscatter?

Abstract Introduction Calibrated integrated backscatter (cIB) may be obtained from bidimensional (2D) strain echocardiography as a quantification measurement of myocardial ultrasound reflectivity. Increased collagen content of the myocardium modifies tissue reflectivity and cIB is suggested as a marker of left ventricular (LV) fibrosis. However, its diagnostic accuracy is not fully established. Aim To assess the correlation between cIB by 2D strain and LV myocardial fibrosis (MF), as evaluated by non-invasive imaging and histopathology. Methods Correlation study from a cohort of 157 patients with severe symptomatic aortic stenosis (AS) referred for surgical aortic valve replacement (AVR). Patients with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of AVR were selected. Two groups of 30 patients were evaluated, with and without late gadolinium enhancement (LGE) at CMR. Integrated Backscatter was obtained at QRS peak in decibels (dB) from both parasternal long axis (PLAX) and apical-three-chamber (A3C) cine clips at Qanalysis. cIB was calculated by subtracting the pericardial intensity from the average of the anteroseptal and basal inferolateral wall values. Correlation analysis was performed for the whole group of patients with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) from Masson´s Trichrome staining. IBS values were compared in both group of patients. Results 60 patients (74 [36-74] years, 45% male) with high gradient (mean gradient: 63±20mmHg), normal flow (45±10mL/m2), preserved ejection fraction (60±9%) AS were included. Basal septal cIB was –9.17±9.45dB and –17.45 (–31.2–10.95) dB from A3C and PLAX views, respectively. These indexes did not correlate with basal septum thickness or global LV mass. Absolute and cIB did not correlate neither with global and regional T1 and ECV values, nor with CVF at EMB. These were not significantly different in both groups of patients and there was no correlation between cIB values and mass of replacement MF in patients with LGE. Conclusion In these cohort of patients with classical severe AS, there was no correlation of cIB with imaging markers of both replacement and diffuse MF. cIB also didn´t correlate with CVF at histopathology. These findings suggest that reflectivity indexes are not suitable for myocardial tissue characterization in this setting.

Impact of autofluorescence for detection of parathyroid glands during thyroidectomy on postoperative parathyroid hormone levels: parallel multicentre randomized clinical trial.

Techniques for autofluorescence have been introduced to visualize the parathyroid glands during surgery and to reduce hypoparathyroidism after thyroidectomy. This parallel multicentre RCT investigated the use of Fluobeam® LX to visualize the parathyroid glands by autofluorescence during total thyroidectomy compared with no use. There was no restriction on the indication for surgery. Patients were randomized 1 : 1 and were blinded to the group allocation. The hypothesis was that autofluorescence enables identification and protection of the parathyroid glands during thyroidectomy. The primary endpoint was the rate of low parathyroid hormone (PTH) levels the day after surgery. Some 535 patients were randomized, and 486 patients received an intervention according to the study protocol, 246 in the Fluobeam® LX group and 240 in the control group. Some 64 patients (26.0 per cent) in the Fluobeam® LX group and 77 (32.1 per cent) in the control group had low levels of PTH after thyroidectomy (P = 0.141; relative risk (RR) 0.81, 95 per cent c.i. 0.61 to 1.07). Subanalysis of 174 patients undergoing central lymph node clearance showed that 15 of 82 (18 per cent) in the Fluobeam® LX group and 31 of 92 (33 per cent) in the control group had low levels of PTH on postoperative day 1 (P = 0.021; RR 0.54, 0.31 to 0.93). More parathyroid glands were identified during operation in patients who had surgery with Fluobeam® LX, and fewer parathyroid glands in the surgical specimen on definitive histopathology. No specific harm related to the use of Fluobeam® LX was reported. The use of autofluorescence during thyroidectomy did not reduce the rate of low PTH levels on postoperative day 1 in the whole group of patients. It did, however, reduce the rate in a subgroup of patients. Registration number: NCT04509011 (http://www.clinicaltrials.gov).

5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer-A Retrospective Analysis.

We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7-19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0-85.7) years. The bDFS rates and late toxicity profile were evaluated. Median treatment time was 10 (7-38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)-G2: 9.1%; G3: 0.5%; genitourinary (GU)-G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.

Is myocardial fibrosis appropriately assessed by 2D strain derived integrated backscatter?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Calibrated integrated backscatter (cIBS) may be obtained from bidimensional (2D) strain echocardiography as a quantification measurement of myocardial ultrasound reflectivity. Increased collagen content of the myocardium modifies tissue reflectivity and cIBS is suggested as a marker of left ventricular (LV) fibrosis. However, its diagnostic accuracy is not established. Aim To assess the correlation between cIBS by 2D strain and LV myocardial fibrosis (MF), as evaluated by non-invasive imaging and histopathology. Methods Correlation study from a cohort of 157 patients with severe symptomatic aortic stenosis (AS) referred for surgical aortic valve replacement (AVR). Patients with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of AVR were selected. Two groups of 30 patients were evaluated, with and without late gadolinium enhancement (LGE) at CMR. IBS was obtained at QRS peak in decibels (dB) from both parasternal long axis (PLAX) and apical three chamber (A3C) cine clips at Qanalysis (Figure 1A). cIBS was calculated by subtracting the pericardial intensity from the average of the anteroseptal and basal inferolateral wall values. Correlation analysis was performed for the whole group of patients with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) from Masson´s Trichrome staining. IBS values were compared in both group of patients. Results 60 patients (73 [68–74] years, 45% male) with high gradient (mean gradient: 64±20mmHg), normal flow (45±10mL/m2), preserved ejection fraction (60±9%) AS. Basal septal cIBS was −9.2±9.5dB and −16.3±7.9dB from A3C and PLAX views, respectively. These indexes did not correlate with basal septum thickness or global LV mass. Absolute and cIBS did not correlate neither with global and regional T1 and ECV values, nor with CVF at EMB (Figure 1B). These were not significantly different in both groups of patients and there was no correlation between cIBS values and mass of replacement MF in patients with LGE. Conclusion In these cohort of patients with classical severe AS, there was no correlation of cIBS with imaging markers of both replacement and diffuse MF. cIBS also didn´t correlate with CVF at histopathology. These findings suggest that reflectivity indexes are not suitable for myocardial tissue characterization in this setting.

Unsupervised machine learning effectively clusters pediatric spastic cerebral palsy patients for determination of optimal responders to selective dorsal rhizotomy

Selective dorsal rhizotomy (SDR) can reduce the spasticity in patients with spastic cerebral palsy (SCP) and thus improve the motor function in these patients, but different levels of improvement in motor function were observed among patients after SDR. The aim of the present study was to subgroup patients and to predict the possible outcome of SDR based on the pre-operational parameters. A hundred and thirty-five pediatric patients diagnosed with SCP who underwent SDR from January 2015 to January 2021 were retrospectively reviewed. Spasticity of lower limbs, the number of target muscles, motor functions, and other clinical parameters were used as input variables for unsupervised machine learning to cluster all included patients. The postoperative motor function change is used to assess the clinical significance of clustering. After the SDR procedure, the spasticity of muscles in all patients was reduced significantly, and the motor function was promoted significantly at the follow-up duration. All patients were categorized into three subgroups by both hierarchical and K-means clustering methods. The three subgroups showed significantly different clinical characteristics except for the age at surgery, and the post-operational motor function change at the last follow-up in these three clusters was different. Three subgroups clustered by two methods could be identified as “best responders”, “good responders” and “moderate responders” based on the increasement of motor function after SDR. Clustering results achieved by hierarchical and K-means algorithms showed high consistency in subgrouping the whole group of patients. These results indicated that SDR could relieve the spasticity and promote the motor function of patients with SCP. Unsupervised machine learning methods can effectively and accurately cluster patients into different subgroups suffering from SCP based on pre-operative characteristics. Machine learning can be used for the determination of optimal responders for SDR surgery.

COVID-19 incidence and vaccination against SARS-Cov-2, influenza, and pneumococcal disease in patients with heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The risk of a severe course of COVID-19 infection increases with age and body weight, is higher in men and in the chronically ill. Patients with cardiovascular diseases, including heart failure (HF), are at risk of severe (various) infections with a higher risk of complications leading to death. The current guidelines of the European Society of Cardiology recommend prophylactic vaccinations in this group of patients against both SARS-COV-2 and other pathogens. Purpose The aim of the study was to analyze the vaccination coverage against pneumococcus, influenza and COVID-19, as well as to assess the incidence and course of COVID-19 infections in the population of patients with HF hospitalized after an episode of acute heart failure (AHF) between 03.2021 and 03.2022. Methods As a part of the prospective Acute Heart Failure Registry (OP-AHF), in the period from 06.2019, data were obtained from 122 patients hospitalized in the ICCU. Inclusion criteria were hospitalization for AHF and the need to use at least one of: intravenous diuretics, catecholamines or mechanical circulatory support. Data on vaccinations against COVID-19 (a/C19), influenza (a/I) and pneumococcus (a/P), as well as COVID-19 incidence, were collected in a 12-month follow-up from 90 patients. Results COVID-19 infection occurred in 27% of patients (24 of 90 patients). In the studied population, fewer cases of the disease occurred in patients over 65 years of age compared to the younger ones (20% vs 36%, p = 0.08) and a significant proportion of them were male (96% vs 4% women).Among patients with a history of COVID-19 infection [C19(+)] compared to patients without infection [C19(-)], slightly more patients were active smokers (42% vs 39%, p = 0.85), more had diabetes (42% vs 27%, p = 0.19) and hypertriglyceridemia (25% vs 8%, p = 0.03). Patients C19(+) had a higher BMI (34 vs 29 in C19(-), p = 0.01) and lower left ventricle ejection fraction at discharge (33 vs 40, p = 0.18). The most common etiologies of HF in C19(+) patients were ischemic (10 of 24 patients, 42%) and valvular (10 of 24 patients, 42%). The vaccination coverage a/C19 in the whole group of patients was 69% (62 out of 90), of which a higher percentage of vaccinations was in patients over 65 years of age (75% vs 62%, p = 0.19). The a/I vaccination rate was 11%, with a slightly lower percentage in patients over 65 years of age (10% vs 13%, p = 0.65). Among the studied patients, 58% (52 of 90) were vaccinated with both a/C19 and a/I. However, all patients vaccinated a/I were also vaccinated a/C19. None of the examined patients was vaccinated a/P. Conclusion The COVID-19 pandemic and the widely available information on cardiovascular complications resulted in an increase in vaccination among a group of patients at high risk for complications. However, there is still unsufficient awareness of the need for influenza and pneumococcal vaccination as a prevention of serious post-infection complications.

Early outcomes of thoracoscopic trans-mitral myectomy in obstructive hypertrophic cardiomyopathy patients with left midventricular obstruction

Objective: To examine the early effect of thoracoscopic trans-mitral myectomy for hypertrophic cardiomyopathy patients with left midventricular obstruction. Methods: From April 2020 to July 2021, 10 hypertrophic cardiomyopathy patients with left midventricular obstruction underwent thoracoscopic trans-mitral myectomy at Guangdong Provincial People's Hospital. The whole group of patients consisted of 7 males and 3 females aged (52.0±16.4) years (range: 18 to 68 years). The EuroSCORE Ⅱ predicted mortality rate was 1.78% (1.20%) (M(IQR)) (range: 0.96% to 4.86%). The clinical data were collected and analyzed retrospectively to evaluate the clinical efficacy by comparing preoperative and postoperative echocardiographic parameters using paired t-test, paired Wilcoxon test or Fisher exact test, including left ventricular outflow tract peak pressure gradient, maximum interventricular septum thickness, systolic anterior motion of the anterior mitral leaflet and so on. The safety was determined by summarizing the incidence of perioperative and follow-up complications. Results: All the procedures successed with no conversion to median sternotomy, septal defect, ventricular rupture. There was no in-hospital 30-day death, neither serious complications like permanent pacemaker implantation, re-sternotomy for bleeding, low cardiac output syndrome, stroke, or multiple organ dysfunction syndrome. The left ventricular outflow tract obstruction was effectively relieved in all patients expect a patient developed residual obstruction. Compared with that of pre-operation, the thickness of the interventricular septum was significantly reduced from (22.1±4.0) mm to (10.3±1.7) mm (t=10.693, P<0.01), while the left ventricular outflow tract peak pressure gradient was significantly reduced from (81.7±21.1) mmHg to 12.3 (11.5) mmHg (Z=-2.805, P<0.01) (1 mmHg=0.133 kPa). Conclusion: Thoracoscopic trans-mitral myectomy is an effective and safe procedure for hypertrophic cardiomyopathy patients with left midventricular obstruction.

Hematopoietic stem cell transplantation for inborn errors of immunity: 30-year single-center experience.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an effective treatment for a variety of inborn errors of immunity (IEI). We report the experience of children affected by IEI who received allo-HSCT over a period of 32 years at IRCCS Istituto Giannina Gaslini, Genoa, Italy. HSCTs were performed in 67 children with IEI. Kaplan-Meier estimates of overall survival (OS) rate at 5 years in the whole group of patients was 83.4% after a median follow-up of 4 years. Median age at transplant was 2.5 years. Eight allo-HSCTs were complicated by either primary or secondary graft failure (GF), the overall incidence of this complication being 10.9%. Incidence of grade 3-4 acute GvHD (aGvHD) was 18.7%, significantly lower in the haploidentical transplant cohort (p = 0.005). Year of transplant (≤2006 vs. >2006) was the main factor influencing the outcome. In fact, a significant improvement in 5-year OS was demonstrated (92.5% >2006 vs. 65% ≤2006, p = 0.049). Frequency of severe aGvHD was significantly reduced in recent years (≤2006 61.5%, vs. >2006 20%, p = 0.027). A significant progress has been the introduction of the TCR αβ/CD19-depleted haploidentical platform, which was associated with the absence of severe aGvHD. However, it was associated with 23.5% incidence of GF. All but one patient experiencing GF in the this specific cohort were successfully retransplanted. In summary, allo-HSCT is confirmed to be an effective treatment for children with IEI, even in the absence of an HLA-matched donor.

Phenotypes of Chronic Rhinosinusitis and Peripheral Blood Leukocytes Parameters in Elderly Patients.

Background and Objectives: Chronic rhinosinusitis (CRS) is a common disease that can be differentiated into two phenotypes, with or without polyps (CRSwNP) or CRSsNP), which may be unilateral (UNIL) or bilateral (BIL). CRS may have an impact on absolute neutrophils and lymphocytes count in peripheral blood. The aim of the study was to investigate whether the incidence of a specific CRS phenotype changes with age and to compare the values of neutrophils, lymphocytes and neutrophil-to-lymphocyte ratio in the peripheral blood between groups of patients below and above 65 years of age with different CRS phenotypes. Material and Methods: A total of 235 patients aged 65 and over were examined, including 140 (59.6%) males. The group of patients &lt;65 years of age comprised 160 subjects, including 103 (64.4%) males. In both groups, the sequence of frequency of particular phenotypes was similar: the most common phenotype was bilateral CRSwNP followed by CRSsNP BIL, CRSsNP UNIL, and finally, CRSwNP UNIL. Direct comparisons between determined phenotype in both groups of different ages revealed that, in the group ≥65 years, CRSwNP BIL occurred significantly more often than in the group &lt;65 years of age. In fact, in the &lt;65 group, bilateral CRSsNP was more common. The absolute neutrophils and lymphocytes counts were significantly higher in the whole group of patients with CRS ≥65 years of age and absolute number of neutrophils was higher in ≥65 years of age group with bilateral CRSsNP. Conclusions: The higher number of neutrophils in the whole ≥65 years of age group and in older patients with bilateral CRSsNP may indicate that CRS, despite of phenotype, may be an important source of infection that requires surgical treatment in elderly patients as well.

Interobserver Variations in Target Delineation in Intensity-Modulated Radiation Therapy for Nasopharyngeal Carcinoma and its Impact on Target Dose Coverage.

To investigate the differences between physicians in target delineation in intensity-modulated radiation therapy for nasopharyngeal carcinoma as well as their impact on target dose coverage. Ninety-nine in-hospital patients were randomly selected for retrospective analysis, and the target volumes were delineated by 2 physicians. The target volumes were integrated with the original plans, and the differential parameters, including the Dice similarity coefficient (DSC), Hausdorff distance (HD), and Jaccard similarity coefficient (JSC) were recorded. The dose-volume parameters to evaluate target dose coverage were analyzed by superimposing the same original plan to the 2 sets of images on which the target volumes were contoured by the 2 physicians. The significance of differences in target volumes and dose coverage were evaluated using statistical analysis. The target dose coverage for different sets of target volumes showed statistically significant differences, while the similarity metrics to evaluate geometric target volume differences did not. More specifically, for PGTVnx, the median DSC, JSC, and HD were 0.85, 0.74, and 11.73, respectively; for PCTV1, the median values were 0.87, 0.77, and 11.78, respectively; for PCTV2, the median values were 0.90, 0.82, and 16.12, respectively. For patients in stages T3-4, DSC, and JSC were reduced but HD was increased compared to those in stages T1-2. Dosimetric analysis indicated that, for the target volumes, significant differences between the 2 physicians were found in D95, D99, and V100 for all the target volumes (ie, PGTVnx, PCTV1, and PCTV2) across the whole group of patients, as well as in patients with disease stages T3-4 and T1-2. The target volumes delineated by the 2 physicians had a high similarity, but the maximal distances between the outer contours of the 2 sets were significantly different. In patients with advanced T stages, significant differences in dose distributions were found, stemming from the deviations of target delineation.