Total Group Of Patients Research Articles

P-566 Clinical parameters that predict a premature LH rise in patients undergoing ovarian stimulation for IVF

Abstract Study question What are the clinical parameters that can predict a premature LH rise or LH surge in patients undergoing ovarian stimulation for IVF? Summary answer The parameters predicting an early LH rise are: Age, BMI, day 3 LH levels, LH on day of antagonist administration, and number of stimulation days. What is known already Normal reproductive function and fertility require precise regulation of FSH and LH secretion. In IVF stimulation cycles some patients will have an early LH rise even while being treated with a GnRH antagonist. Previous studies have shown a possible link of LH rise with ovarian response to gonadotropins. Nevertheless, little is known of which clinical parameters can predict this LH rise; an occurrence that may necessitate cycle cancellation. Early prediction of premature LH rise will enable us to foresee this unwanted hypophyseal event, and in turn may lead to early antagonist administration and/or early triggering for oocyte retrieval. Study design, size, duration A retrospective study enrolling 382 patients who underwent IVF treatment at Rambam Medical Center (2015 - 2021): age 34.1±6.7 years; BMI 25.0±5.1 kg/m²; AFC 11.2±7.1; day 3 FSH 7.2±2.9U/L; day 3 LH 6.4±4.3U/L; eggs retrieved 8.0±6.1; fertilizations 4.7±4.2. Patients were stimulated with rFSH (Gonal F)/rFSH+LH (Pergoveris)/ highly purified urinary FSH+hCG(Menopur); GnRH antagonist (Cetrotide/ Orgalutran) was administered using a flexible protocol; triggering of ovulation was performed using GnRHagonist and/or hCG, based on estradiol levels. Participants/materials, setting, methods Clinical parameters included from chart data were: age; BMI; estradiol, progesterone, LH and FSH levels at day3/ day of antagonist administration/ and last day before triggering; total stimulation days and total FSH dose. In order to establish a model to predict premature LH rise we performed multiple linear regression using ANOVA with a confidence interval of 0.95 considered significant. A machine learning based model was used to test the accuracy of our model using Python. Main results and the role of chance An LH rise was calculated as the difference between pre-trigger- and basal LH levels. For the total group of patients this LH rise was significantly predicted by patient age; BMI; LH levels at day 3 and LH at the day of antagonist administration; and total stimulation days (R = 0.742, R²=0.55, p < 0.001). Importantly, when analyzing the data of specific age groups, the prediction of the model was strongest in the young patients (age 25-30: R = 0.94, R²=0.88, p < 0.001) and weakest in the older patients (age > 41: R = 0.48,R²=0.23, p = 0.003). Accordingly, using a machine learning model in which a Python based algorithm is trained by analyzing 80% of the data, we were able to successfully predict the remaining 20%: mean squared error of 4.32 and 82.3 in the young- and old patient groups respectively. Interestingly, 21 patients demonstrated a “full LH surge” as defined by a more than two fold increase in LH levels. These patients were also predicted by a similar model (LH levels at day 3 and at the day of antagonist administration, BMI and total FSH dose; R = 0.89, R²=0.80, p = 0.015). Limitations, reasons for caution This is a retrospective study and its conclusions need to be validated by a prospective randomized trial. Wider implications of the findings Using machine-learning based analysis of patient data from IVF cycles, we were able to predict patients at risk for premature LH-rise and/or LH-surge. Interestingly, the prediction of this model was strongest in young patients. Utilizing this model will help prevent IVF cycle cancellation and better timing of ovulation triggering. Trial registration number NA

PB1857: NRF2 MODULATORS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS: A POSSIBLE NEW THERAPEUTIC APPROACH

Background: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of resting clonal B lymphocytes in peripheral blood, bone marrow and secondary lymphoid organs. This disease has a notable heterogeneous clinical course, with different prognosis and distinct treatment needs. Oxidative stress (OS) is one of the mechanisms important in CLL development and progression. OS state consists in an unbalance between the production of reactive oxygen species (ROS) and the ability to neutralize them by antioxidant defenses. The nuclear factor erythroid 2–related factor 2, NRF2, is a transcription factor that regulates the expression of several antioxidants and detoxification systems and works as a protective mechanism in normal cells against malignant transformation. However, during the tumorigenic process, NRF2 protects tumor cells from OS effects compromising the therapeutic efficacy. Aims: The study aims to evaluate the therapeutic potential of two NRF2 modulators, Brusatol and ML385, in B cells from CLL patients. Methods: Peripheral blood mononuclear cells (PBMCs) from 13 CLL patients (stage initial, Binet A/B, n=8; advanced stage, Binet C, n=5) were isolated by density gradient using Ficoll-Paque Premium. PBMCs where immediately incubated in absence and presence of Brusatol and ML385. The cytotoxic effect was evaluated 24h and 48h after incubation by fluorometric microculture cytotoxicity assay. After 24h incubation with Brusatol (100nM) and ML385 (100μM) cells were stained with anti-CD5-PerCP, anti-CD19-APC and Annexin V, to assess cell death by flow cytometry. The statistical analysis was carried out in the total CLL patient group and in risk groups. The results were considered statistically significant when p<0.05. Results: CLL patients presented 93,3% (±3.7%) of neoplastic B cells (CD5+/CD19+), 3,7% (±3,0%) of normal B cells (CD5-/CD19+) and 2,7% (±1,2%) of normal T cells (CD5+/CD19-), with no statistical differences regarding staging groups. Brusatol induced a decreased survival rate in CLL cells comparing to ML385, being this effect dependent on the dose and disease stage. Brusatol induced a higher reduction of cell viability in PBMCs from advanced disease patients (Binet C). ML385 did not induced a significant decrease in cell survival, nevertheless its effect is more marked in advanced stage patients at 48h post incubation. IC50 was only achieved at 48h in advanced stage patients and corresponds to 65nM for Brusatol and to 114µM for ML385. NRF2 modulators induced a cytotoxic effect mainly mediated by apoptosis. Cytotoxicity induced by both drugs was more evident in neoplastic B cells, with no significant cytotoxicity in normal B and T cells. In PBMCs incubated with Brusatol an increase of neoplastic B cells in apoptosis about 68% was observed (Brusatol: 91,9% ± 7,1%; Control: 23,7% ± 4,3%), and of 34% in cells incubated with ML385 (ML385: 57,9% ± 10,2%; Control: 23,7% ± 4,3%). No differences of apoptotic cells were observed in advanced stage groups. Summary/Conclusion: Our results showed that neoplastic cells from CLL patients were sensitive to NRF2 modulators, suggesting that these drugs may constitute a new therapeutic approach in CLL patients, particularly in CLL patients in advanced stage. We also demonstrated the low cytotoxic effect of these modulators in normal lymphocytes and its higher efficacy in neoplastic cells from advanced stage patients. Altogether, these results show that these NRF2 modulators have an effect directed to the neoplastic cell and suggest a possible involvement of NRF2 on CLL development and progression. # equally contributing authors.

Cyclic Vomiting Syndrome in the Emergency Department: A 10-Year Review of Clinical Presentation and Management.

The aims of the study were (1) to determine how frequently patients with cyclic vomiting syndrome (CVS) present to the pediatric emergency department (ED) with CVS-related symptoms, (2) to identify variables in clinical presentation that occur frequently in patients with multiple ED visits, and (3) to compare ED management of CVS with recommended guidelines. This study is a retrospective chart review of all ED visits for CVS between April 1, 2008, and April 1, 2018, at a single center. Patients were identified from a master list of patients diagnosed with CVS in a pediatric gastroenterology clinic at the same center between June 1, 2004, and June 19, 2018. Of the 181 CVS clinic patients identified, 65 had visited to the ED (35.9%). Two hundred twenty-eight visits met inclusion criteria. A total of 42.5% of these visits were made by a small number of high-intensity patients (n = 6) who had an average of 16.1 visits each. These patients represented less than 10% of the total patient group. Patients with frequent visits had longer visits (536.52 vs 380.55 minutes), more frequent hospital admissions (57.73% vs 29.01%), and more visits to the ED before a formal diagnosis of CVS was made (5.83 vs 1.22), but few other distinguishing characteristics. Only 27% of eligible visits were managed with an available order set, and management varied from recommended guidelines. An ambiguous presentation makes the identification and consistent management of CVS in the ED difficult. Physicians should consider CVS for patients who present multiple times with unremitting vomiting to ensure appropriate referral for diagnosis and prophylactic treatment. Future studies are warranted to evaluate anticipatory processing and treatment of the "high-intensity patients" who account for much of the clinical morbidity and resource utilization.

Genetic polymorphisms related to the vitamin D pathway in patients with cirrhosis with or without hepatocellular carcinoma (HCC).

ObjectiveTo evaluate the association of genetic polymorphisms of vitamin D transporter protein (DBPrs4588 and DBP-rs7041) and cytochrome P450-24A1 (CYP24A1-rs6013897) in patients with cirrhosis with or without hepatocellular carcinoma (HCC), including demographic/clinical/biochemical profiles.MethodsA total of 383 individuals were studied, considering the total group (TotalG) of patients with cirrhosis (TotalG: N = 158) with or without HCC, distributed into Group 1 (G1): cirrhosis and HCC; Group 2 (G2): isolated cirrhosis; and 225 individuals without hepatopathies (G3). Polymorphisms were analysed by real-time polymerase chain reaction. An alpha error of 5% was admitted.ResultsCYP24A1-rs6013897 predominated the genotype with at least one polymorphic allele (_/T) in G1 (98.3%) versus G2 (88.8%; p = 0.0309). There was a moderate positive correlation between vitamin D and parathyroid hormone in patients (TotalG: R2 = 0.3273). Smoking, alcoholism and diabetes mellitus (DM) stood out as independent factors for cirrhosis, as well as for cirrhosis with HCC, except for smoking, adding, in this case, advanced age, male gender, polymorphic allele of CYP24A1-rs6013897, viral hepatitis and high levels of serum gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP) and creatinine. An increase in survival was observed in the presence of the polymorphic allele of DBP-rs7041 (p = 0.0282).ConclusionCYP24A1-rs6013897 is associated with cirrhosis and HCC as a predictor, while DBP-rs4588 is associated with reduced vitamin D, and DBP-rs7041 provides increased survival, suggesting a protective characteristic. Advanced age, alcoholism, DM, viral hepatitis and high levels of GGT, AFP and creatinine are also confirmed as predictors of HCC and cirrhosis, while smoking, alcoholism and DM for isolated cirrhosis only.

MO236: Serological Markers of Celiac Disease in Patients With IGA-Nephropathy: Prevalence and Diagnostic Significance

Abstract BACKGROUND AND AIMS It is known that IgA-nephropathy (IgAN) can be secondary to liver disease, skin disease, lung disease, etc. There is also evidence of an association between IgAN and celiac disease. In the Russian population, there are no studies aimed at identifying the prevalence of IgAN and celiac disease in adult. The aim of this study was to determine the incidence of celiac antibody (СА) in patients with IgAN and to compare the clinical and laboratory features within groups. METHOD fifty patients with IgAN were included in the study. Of these, 46 (92%) were male and 4 (8%) were female, ranging in age from 18 to 63 years. The mean age was 35.9 ± 9.8 years. All patients underwent general clinical blood and urinalysis, daily urinary protein excretion. Serum concentrations of IgA, total protein, albumin, creatinine, urea, uric acid, IgA antibodies to tissue transglutaminase (tTG), to deamidated gliadin peptide (DGP), to endomysium (EMA) and IgA and IgG antibodies to reticulin (ARA) were assessed, GFR was calculated using the CKD-EPI formula, the ‘office’ blood pressure was measured. Patients with positive CA underwent fibrogastroduodenoscopy (FGDS) with biopsy of the retro-bulbar of the duodenum. The results of the celiac marker study were compared in two groups of patients with IgAN. Group I (n = 10) were patients with IgAN and positive CA; Group II (n = 40) were patients with IgAN and negative CA. Statistical analysis of the data was performed using the SPSS 26.0. The null statistical hypothesis of no difference and no relationship was refuted at P &amp;lt; .05. RESULTS Positive serological markers were found in 20% of the total group of patients with IgAN. IgA antibodies to DGP were positive in 100% of cases; one patient had a one-step increase in IgA antibodies to DGP and IgA antibodies to tTG. No increase of antibodies to ARA and EMA was observed in any case. All Group I patients underwent FGDS; changes in the architectonics of the duodenum were not found. Four patients underwent biopsy of the retro-bulbar of the duodenum according to the Marsh histological classification; all biopsies were classified as Marsh 0–1. The mean concentration of protein in the urine of group I patients was 1.36 (0.76–1.58) g/L and statistically significantly higher than in group II patients 0.6 (0.4–0.93) g/L. (Р = .033). The mean daily proteinuria in celiac antibody-positive patients was 2.38 (0.78–2.8) g/day and was statistically significantly higher than in group II patients at 0.7 (0.6–1.36) g/day (Р = 0.049). We compared the incidence of arterial hypertension (AH) depending on the presence of CA in patients with IgAN. Consistent with the findings, the incidence of AH was statistically significantly higher in group I compared to group II (P = .031). The odds of AH in patients with CA were 9 times higher than in patients with negative CA [95% confidence interval (CI) 1.041–77.803]. The mean diastolic blood pressure was statistically significantly higher in group I—105.1 (96–115) mm Hg. compared to group II—92 (86–98) mm Hg (P = .032). We compared the incidence of chronic tonsillitis (CT) according to the presence of CA in patients with IgAN. According to the data, the incidence of CT was statistically significantly higher in group I compared to group II (Р = .023). The likelihood of having CT was 8.2 times higher in patients with positive antibodies than in those with negative CA (95% CI 1.461–46.272). CONCLUSION Although the patients with IgAN and positive CA did not have gastrointestinal symptoms, and FGDS with a biopsy of the retro-bulbar of the duodenum did not provide convincing evidence for a violation of the intestinal architectonics, we found statistically significant deviations in clinical and laboratory in this group of patients. Our preliminary findings suggest that an isolated increase in CA to exacerbate the course of IgAN. Whether the screening detection of CA, without disrupting intestinal architectonics, can be an additional diagnostic and prognostic marker for patients with IgAN remains a matter of debate to date. In the meantime, further research on this issue is needed, both at clinical and experimental level.

Superoxide Dismutase Activity in Male and Female Patients of Different Age with Moderate COVID-19.

The study involved 271 patients (132 men and 139 women) with moderate COVID-19. Superoxide dismutase (SOD) activity in erythrocytes was measured spectrophotometrically. In total group of patients (divided into age groups of 18-35, 36-45, 46-60, and 61-90 years), higher SOD activity was found in the 18-35 age group in comparison with the groups 46-60 years (p<0.01) and 61-90 years (p<0.05). Then, the groups were additionally divided by sex. In men, no differences in enzyme activity were found between the age groups. In women of early reproductive age, SOD activity was higher than in groups 36-45, 46-60, and 61-90 years. The sex differences consisted in higher SOD activity in women aged 18-35 years in comparison with men of this age. These data should be taken into account when choosing the tactics of therapy for patients with moderate COVID-19 course.

Long-Term Cardiac Disease- and Cancer-Associated Mortalities in Patients With Non-Metastatic Stomach Adenocarcinoma Receiving Resection and Chemotherapy: A Large Competing-Risk Population-Based Cohort Study.

BackgroundThe survival of patients with non-metastatic gastric adenocarcinoma (nmGaC), who are receiving more and more frequently chemotherapy, has improved throughout the last decades, while treatment-caused cardiotoxicity remains a major concern. This study aimed to investigate competing causes of mortality and prognostic factors within a large cohort of patients with resected nmGaC, and to describe the heart-specific mortalities of patients undergoing resection and chemotherapy and of all resected patients.MethodsIn this population-based cohort study, data on patients diagnosed with nmGaC from 2004 through 2016, managed with resection with or without chemotherapy, followed up until the end of 2016, and surviving ≥ 1 month were retrieved from the US Surveillance, Epidemiology, and End Results-18 Program. Cumulative mortality functions were calculated. Prognostic factors for heart- and cancer-specific mortalities were evaluated using both multivariable-adjusted Fine-Gray subdistribution and cause-specific hazard functions.ResultsTogether 21,257 patients with resected nmGaC were eligible for analysis with an accumulated follow-up of 73,711 person-years, where 10,718 (50%) also underwent chemotherapy. Mortalities were overestimated when using the Kaplan-Meier method. Heart diseases were the most common non-cancer cause of mortality. Compared with all resected patients, heart-specific mortality of those also receiving chemotherapy was lower overall and especially at older ages. In the total group of patients, the 8-year cumulative mortalities from heart diseases were 4.4% and 2.0% in resected patients and those also receiving chemotherapy, respectively; in patients ≥ 80 years, the heart disease-specific mortalities were as high as 11.1% and 6.5%, respectively. In overall patients undergoing resection, older ages, black ethnicity, and location at gastric antrum/pylorus were associated with increased heart-specific mortality, while more recent period, female sex, Asian/Pacific Islanders, invasion of serosa, and more positive lymph nodes were associated with lower heart-specific mortality; among those further receiving chemotherapy, only the associations with period of diagnosis, age, and ethnicity were significant. Associations with older ages were stronger for heart-specific mortality than for cancer-associated mortality.ConclusionsAmong survivors with resected nmGaC receiving chemotherapy, heart-specific mortality, the most common one among non-cancer causes of mortality, is not higher compared to overall resected patients in this observational study, suggesting that chemotherapy may be relatively safely administered to selected patients under strict indications. Age and ethnicity were major factors associated with heart-specific mortality in both overall resected patients and those further receiving chemotherapy. Overall and stratified cause-specific cumulative incidences of mortality are provided, which can be more clinically useful than the Kaplan-Meier estimates. Our study provides clinically useful evidence for tailored patient management.

High Betaine and Dynamic Increase of Betaine Levels Are Both Associated With Poor Prognosis of Patients With Pulmonary Hypertension.

Background and ObjectiveThe association between plasma betaine levels and cardiovascular diseases (CVDs) has been revealed except for pulmonary hypertension (PH). In this study, we aimed to explore the role of betaine in patients with PH.MethodsInpatients with PH at Fuwai Hospital were enrolled after excluding relative comorbidities. Each patient received at least one follow-up through a clinical visit, and the fasting blood was obtained both at the first and second hospitalization for betaine detection. The primary endpoint was defined as composite outcome events and the mean duration was 14.3 (6.9, 21.3) months. The associations of betaine and changes of betaine (Δbetaine) with disease severity and prognosis were explored.ResultsFinally, a total of 216 patients with PH were included and the medians for betaine plasma levels in the total patients group, low betaine, and high betaine groups were 49.8 (39.0, 68.3) μM, 39.0 (33.5, 44.7) μM, and 68.1 (57.8, 88.7) μM, respectively. High betaine was associated with poor World Health Organization Functional Class (WHO-FC), increased N-terminal pro-brain natriuretic peptide (NT-proBNP), low tricuspid annular plane systolic excursion (TAPSE), and cardiac output index even after adjusting for confounders. Patients with high betaine were over twice the risk to receive the poor prognosis than those with a low level [hazard ratio (HR) = 2.080, (95% CI: 1.033–4.188)]. Moreover, the decrease of betaine level after further treatment was positively correlated to ΔNT-proBNP indicating Δbetaine might be an effector of disease severity, and dynamic increase of betaine was also associated with poor prognosis in PH.ConclusionBetaine was associated with disease severity and might be an effector in PH. Patients with increased levels or with dynamic rise of betaine heralded a poor prognosis.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia

目的探讨单倍型造血干细胞移植（haplo-HSCT）治疗移植前微小残留病（Pre-MRD）阳性急性B淋巴细胞白血病（B-ALL）是否较全相合同胞造血干细胞移植（MSDT）具有生存优势，以及该作用是否受Pre-MRD的影响。方法对2009年6月至2018年6月在北京大学血液病研究所接受异基因造血干细胞移植（allo-HSCT）的998例移植前处于完全缓解（CR）的B-ALL患者进行回顾性分析，其中haplo-HSCT组788例、MSDT组210例，移植前用多参数流式细胞术（MFC）检测MRD水平。结果①全部998例B-ALL患者中，997例获得持续的完全供者嵌合状态，移植后100 d中性粒细胞、血小板植入率分别为99.9％（997/998）、95.3％（951/998），Ⅱ～Ⅳ度急性移植物抗宿主病（GVHD）发生率为26.6％（95％CI 23.8％～29.4％），3年慢性GVHD累积发生率为49.1％（95％CI 45.7％～52.4％），移植后3年白血病累积复发率（CIR）为17.3％（95％CI 15.0％～19.7％），非复发死亡率（NRM）为13.8％（95％ CI 11.6％～16.0％），移植后3年无白血病生存（LFS）率、总生存（OS）率分别为69.1％（95％CI 66.1％～72.1％）、73.0％（95％CI 70.2％～75.8％）。②Pre-MRD阳性组（282例）患者移植后3年CIR高于Pre-MRD阴性组（716例）［31.6％（95％CI 25.8％～37.5％）对14.3％（95％CI 11.4％～17.2％），P<0.001］。③在Pre-MRD阳性组中，haplo-HSCT患者（219例）移植后3年CIR低于MSDT患者（63例）［27.2％（95％CI 21.0％～33.4％）对47.0％（95％CI 33.8％～60.2％），P＝0.002］。④全部998例患者按照Pre-MRD结果分为阴性组（716例）、<0.01％组（46例）、0.01％～<0.1％组（117组）、0.1％～<1％组（87例）、≥1％组（32例）；5组患者中，<0.01％组haplo-HSCT患者（40例）移植后3年CIR低于MSDT患者（6例）［10.0％（95％CI 0.4％～19.6％）对32.3％（95％CI 0％～69.9％），P＝0.017］，0.01％～<0.1％组haplo-HSCT患者（81例）移植后3年CIR也低于MSDT患者（36例）［20.4％（95％CI 10.4％～30.4％）对47.0％（95％CI 29.2％～64.8％），P＝0.004］；其他三组中，haplo-HSCT和MSDT患者移植后3年CIR差异无统计学意义。⑤在Pre-MRD<0.1％组（163例）中，haplo-HSCT患者（121例）移植后3年CIR低于MSDT患者（42例）［16.0％（95％CI 9.4％～22.7％）对40.5％（95％ CI 25.2％～55.8％），P<0.001］，3年LFS率、OS率均高于MSDT组［78.2％（95％CI 70.6％～85.8％）对47.6％（95％CI 32.2％～63.0％），P<0.001；80.5％（95％CI 73.1％～87.9％）对54.6％（95％CI 39.2％～70.0％），P<0.001］，两组3年NRM差异无统计学意义［5.8％（95％CI 1.6％～10.0％）对11.9％（95％CI 2.0％～21.8％），P＝0.188］。多因素分析显示，haplo-HSCT是Pre-MRD<0.1％组移植后低CIR（HR＝0.248，95％CI 0.131～0.472，P<0.001）、高LFS率（HR＝0.275，95％CI 0.157～0.483，P<0.001）和高OS率（HR＝0.286，95％CI 0.159～0.513，P<0.001）的独立影响因素。结论haplo-HSCT治疗Pre-MRD<0.1％的B-ALL患者较MSDT具有生存优势。

Pre-treatment visualization of predicted radiation-induced acute alopecia in brain tumour patients

Background and purposeTemporary alopecia is a common side-effect in brain tumour patients receiving cranial radiotherapy with a significant psychological burden for the affected patient. The purpose of this study was to generate a method in our treatment planning system (TPS) to visualize the expected radiation-induced alopecia 4 weeks after treatment, in order to inform the patients thereupon before the start of radiotherapy. Material and methodsA pilot study was conducted in ten patients receiving hypo- (HF) or conventionally fractionated (CF) photon beam Volumetric Modulated Arc Therapy (VMAT) for an intracranial lesion. Dose calculations were correlated to visible alopecia four weeks after the end of treatment to create a structure predictive of alopecia in our TPS. These alopecia structures for both fractionation schedules were validated in two cohorts of 69 HF and 78 CF patients undergoing radiotherapy between 2016 and 2019. ResultsIn the pilot cohort, a total physical dose of 4 Gy for HF and 12.6 Gy for CF radiotherapy were found to be predictive of alopecia 4 weeks after treatment. Applying these doses to our validation cohort, we found an accurate prediction of alopecia in 59/69 (86%) HF and 73/78 (96%) CF patients. For the total patient group of 147 patients, the predicted amount of alopecia was accurate in 90% of the cases. All inaccurate predictions overestimated the expected extent of alopecia. ConclusionThe presented straightforward method to visualize predicted alopecia 4 weeks after treatment has proven to predict the extent alopecia highly accurate in the vast majority of patients. Sharing these results with the patients pre-treatment may result in stress reduction before cranial irradiation.

Long-term Return to Sports After Anterior Cruciate Ligament Injury: Reconstruction vs No Reconstruction—A Comparison of 2 Case Series

Background: Reconstruction is considered to provide the best opportunity for return to sports (RTS) after anterior cruciate ligament (ACL) rupture. However, recent studies report that <50% of athletes return to preinjury sporting levels and that RTS rates at 1 year after injury are the same for athletes undergoing reconstruction and nonoperative management. Long-term studies are essential to confirm these findings and guide decisions regarding surgery. Purpose: First, to compare long-term sports participation after ACL reconstruction and nonreconstruction and, second, to relate RTS level to strength and stability. Study Design: Cohort study; Level of evidence, 3. Method: Patients with ACL deficiency (n = 101) who were referred for physical therapy at the time of diagnosis were followed long term: 56 were treated surgically 2.5 years (interquartile range [IQR], 1-4) after injury and 45 were treated nonoperatively. At long-term follow-up, the reconstructed group was at 9 years (IQR, 7-11) after injury and aged 33.3 ± 6.2 years (mean ± SD, 70% male; 61% meniscal injury), and the nonreconstructed group was at 11 years (IQR, 7-14) after injury and aged 38.7 ± 8.3 years (67% male; 58% meniscal injury). Measures of objective stability, subjective stability, and quadriceps/hamstring strength were compared between groups using independent-samples t tests. Current RTS level, scored on a 6-point scale, was compared between groups using chi-square tests. Spearman rho correlated RTS with outcome measures. Results: Of the total group of patients, 96% with reconstruction and 93% without continued to play sports. In the reconstructed and nonreconstructed groups, 4% and 7% did not RTS, and 8% and 17% returned to safe sports, respectively: 13% and 12% to running, 20% and 26% to sports involving limited twisting, 12% and 24% to recreational pivoting sports, and 43% and 14% to competitive pivoting sports. The only significant difference was in return to competitive pivoting sports (P = .003). Five patients with reconstruction ruptured the contralateral ACL, and 1 ruptured his graft. Most patients treated nonoperatively modified their sports participation. Their RTS levels correlated significantly with quadriceps strength (r = 0.65; P < .001), hamstring strength (r = 0.721; P < .001), and subjective stability (r = 0.405; P = .01). Conclusion: Surgically treated patients returned to competitive pivoting sports at 3 times the rate of those managed nonoperatively, confirming that reconstruction provides the best opportunity for continued participation in competitive pivoting sports. Regardless of grouping, RTS correlated with modifiable factors, including strength and stability. Higher rates of subsequent injuries observed after reconstruction may result from increased participation in competitive pivoting sports.

An easy and practical prognostic parameter: tumor-stroma ratio in Luminal, Her2, and triple-negative breast cancers.

The stroma surrounding the tumor cells is important in tumor progression and treatment resistance, besides the properties of tumor cells. Studies on the tumor stroma characteristics will contribute to the knowledge for new treatment approaches. A total of 363 breast cancer patients were evaluated for the tumor-stroma ratio. The percentage of stroma was visually assessed on hematoxylin-eosin stained slides. The cases of tumor-stroma ratio more than 50% were categorized as tumor-stroma ratio high, and those less than 50% and below were categorized as tumor-stroma ratio low. Tumor-stroma ratio-high tumors had shorter overall survival (p=0.002). Disease-free survival tended to be shorter in tumor-stroma ratio-high tumors (p=0.082) compared with tumor-stroma ratio-low tumors. Tumor-stroma ratio was an independent prognostic parameter for the total group of patients (p=0.003) and also axillary lymph node metastasis and tumor-stroma ratio was statistically associated (p=0.004). Also, tumor-stroma ratio was an independent prognostic parameter in node-positive Luminal A and B subgroups for overall survival (p<0.001). Tumor-stroma ratio is an independent prognostic parameter that can be evaluated quite easily in all molecular subtypes of all breast cancers and does not require extra cost and time to evaluate.

Brainstem Cavernous Malformations Management: Microsurgery vs. Radiosurgery, a Meta-Analysis

Given the rareness of available data, we performed a systematic review and meta-analysis on therapeutic strategy microsurgical resection and stereotactic radiosurgery (SRS) for brainstem cavernous malformations (BSCMs) and assessed mortality, permanent neurological deficits (PNDs), rebleeding rate, and patients who require reintervention to elucidate the benefits of each treatment modality. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) were used for protocol development and manuscript preparation. After applying all inclusion and exclusion criteria, six remaining articles were included in the final manuscript pool. In total, this meta-analysis included 396 patients, among them 168 patients underwent microsurgical treatment and 228 underwent SRS. Findings of the present meta-analysis suggest that regarding the total group of patients, in terms of mortality, late rebleeding rate, and PNDs, there was no superiority of the one method over the other. Applying the leave-one-out method to our study suggests that with low robust of the results for the bleeding rate and patients who require reintervention outcome factor, there was no statistical difference among the surgical and SRS treatment. Microsurgical treatment of BSCMs immediately eliminates the risk of rehemorrhage; however, it requires complete excision of the lesion and it is associated with a similar rate of PNDs compared with SRS management. Apparently, SRS of BSCMs causes a marked reduction in the risk of rebleeding 2 years after treatment, but when compared with the surgical treatment, there was not any remarkable difference.

Hymecromone Administration in Real Clinical Practice: Results of the Prospective Multicentre Observational Study in the Republic of Kazakhstan

Introduction. This multicentre prospective non-interventional observational study was conducted to obtain additional data about Odeston efficacy and safety in routine clinical practice. The objectives of the study included collection of clinical characteristics of patients, evaluation of Odeston effects in treatment of biliary pain and changes in the gallbladder emptying, evaluation of compliance to therapy, and treatment effect satisfaction.Materials and methods. The study was conducted from July 2020 to April 2021 at the premises of 60 study sites in 4 cities of the Republic of Kazakhstan. Patients having indications for Odeston administration according to the patient leaflet were enrolled. The study included 2 patient visits and an intermediate telephone contact. A visual analogue scale and RAPID questionnaire were used to characterise biliary pain; severity of associated symptoms, bowel habit and a quality of life according the SF-12 were also assessed. A rate of a ≥50 % reduction in symptom severity was used as a primary efficacy criterion; a rate of a ≥10 improvement in the SF-12 quality of life score was used as a secondary efficacy criterion. Compliance to treatment was evaluated using a number of days on Odeston. Treatment satisfaction was assessed using 5 grades.Results. 877 patients, 68.2 % of females and 31.8 % of males, were included in the study; the mean age was 46.0 ± 14.9 years. Primary functional biliary disorder was diagnosed in 65.3 % of patients, chronic non-calculous cholecystitis — 51.4 %, uncomplicated gallbladder disease — in 8.9 %, biliary sludge — 38.4 %, sphincter of Oddi functional disorder — 5.3 % of patients. A dose of Odeston was prescribed at the discretion of the physician. Group A patients received 600 mg (n = 89), group B received 1200 mg of Odeston a day (n = 788). In group B, an incidence of pronounced pain interference with daily living activities was higher. In both groups, the mean VAS scores were reduced to 1 point on treatment, a primary efficacy criterion was achieved in 77.3 % of patients in group A and in 79.8 % of patients in group B, р &lt; 0.05. In both groups, a reduction in the incidence of constipation and diarrhea (р &lt; 0,001) and an increase in the mean scores of physical and mental functioning were noted (р &lt; 0.001, though a secondary efficacy criterion was not achieved (a ≥10 change in the SF-12 score). A prevalence of ultrasonographic sings of biliary sludge was reduced, and an increased gallbladder emptying was observed (p &lt; 0.001). 77.4 % of patients in a total group of patients reported about drug administration for 21 days. A number of patients who were completely satisfied with treatment was higher in group B (p = 0.027).Conclusions. It was found that biliary pain interfered with daily living activities and commonly accompanied by other symptoms of gastrointestinal dysmotility. Odeston effectively reduces the severity of biliary pain, corrects dyspeptic disorders and normalizes stool pattern in patients with functional and organic diseases of the biliary system. Treatment satisfaction was higher with a dose of 1200 mg a day, particularly in more pronounced interference of pain with daily living activities.

Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

PurposeMetastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC.Materials and MethodsWe retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics.ResultsThe patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019).ConclusionsPatients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Femoral Head and Liner Exchange in Patients with Atraumatic Dislocation. Results of a Retrospective Study with 6 Years Follow-Up.

Background and Objectives: Femoral head and liner exchange is an established treatment for polyethylene wear but has had a more limited role in the treatment of other conditions including dislocation, because of concerns about an increased postoperative dislocation rate. Some authors have considered dislocation associated with polyethylene wear to be a contraindication for this procedure. Materials and Methods: Our retrospective review evaluated the outcome of head and liner exchange in a small consecutively operated heterogeneous cohort of 20 patients who presented with dislocation unrelated to trauma, component malposition or component loosening. Of this group, 12 had prior primary total hip arthroplasty, and 8 had prior revision total hip arthroplasty, and included 4 patients with prior revision for dislocation. Mean follow-up was 6 ± 3.5 years (range 1–145 months). Results: Kaplan–Meier analysis revealed a revision-free implant survival from any cause of 80% (confidence interval 95%:64.3–99.6%) at 5 years after head and liner exchange (index surgery). At final follow-up, 83.3% of patients (n = 10) with prior primary total hip arthroplasty and 62.5% of patients (n = 5) with prior revision total hip arthroplasty, had not required subsequent revision for any cause. None (0%) of the primary total hip arthroplasty group and 3 (38%) of the revision arthroplasty group had required revision for further dislocation. Of the eight revision arthroplasty patients, four had a prior revision for dislocation and three of these four patients required further revision for dislocation after index surgery. The fourth patient had no dislocation after index surgery. One additional patient who had prior revision surgery for femoral component fracture suffered dislocation after index surgery, but was successfully treated with closed reduction. Conclusions: In our study population, femoral head and liner exchange was an effective treatment option for patients with prior primary total hip arthroplasty and also for a highly select group of revision total arthroplasty patients with no prior history of dislocation. Femoral head and liner exchange does not appear to be a viable treatment option for patients who have had revision total arthroplasty after prior dislocations.

Нетрадиційні засоби фізичної терапії при вертеброгенному болю в області попереку

To assess the impact of the proposed non-traditional physical therapy program (Su Jock therapy, yoga therapy) on patients with vertebrogenic pain in the lumbar region in terms of increased pain. Materials and methods: In order to assess the condition of patients prior to the introduction of the program, questionnaires and spinal function research methods were used. The total group of patients (28 patients) was randomly divided into a basic and control group of 14 patients. The core group worked on the developed program, the control group on the treatment facility program. Results: Based on the results of the survey, a three-week rehabilitation program for major group patients was developed and implemented, including Su Jock therapy and a set of yoga therapy exercises. Conclusions: A comparison of the results of the repeated survey of the nature of pain has revealed a larger number of patients in the core group who have stopped complaining during the observed movements

Somatostatin receptors scintigraphy prioritization criteria based on net patient epidemiological profile: a bi-centric study

This study aimed to create a generic profile of patients with NETs and to establish the prioritization criteria for somatostatin receptors scintigraphy (SRS), within the NETs diagnostic algorithm, being the first study of this kind conducted in Romania. Material and methods: A bi-centric, retro-prospective study comprising 103 patients with NETs, evaluated through 99mTc-TOC SRS, in two nuclear medicine departments from “Sf. Spiridon” County Clinical Emergency Hospital Iasi, Romania and Center of Nuclear Medicine, University Clinical Center of Kragujevac, Serbia. We analyzed the clinical-paraclinical features of included patients, as a starting point for streamlining the selection of patients for SRS. Results and discussion: The total group of patients included 47.57 % men and 52.43 % women, the age varying between 21-83 years. The most frequent primary NETs were represented by pNETs, and GI-NETs and the symptoms were nonspecific for majority of analyzed patients. Both prospective and retrospective analysis showed that SRS was followed by positive results. For prospectively analyzed patients, due to the used customized sheets, it was extremely easy to identify four SRS prioritization criteria. Conclusions: This study could outline the profile of patients with NETs, as the starting point for streamlining patient selection for SRS. The four prioritization criteria proposed by us could guide the diagnostic algorithm.

Effects of silodosin, darifenacin, and combination therapy for the treatment of ureteral stent related discomforts

Background: To evaluate the effect of silodosin, darifenacin and combination therapy of two agents in improving the lower urinary tract symptoms of patients with indwelling double-J ureteral stents.Methods: A total of 150 patients underwent placement of a double-J ureteral stent after retrograde ureteroscopy for urinary stone disease. All patients received polyurethane double-J ureteral stents (4 Fr and length 26 cm), which were removed at a mean of around 14 days postoperatively. A total of 40 patients were given no medication (group 1), 39 patients were given silodosin 4 mg once daily (group 2), 40 patients were given darifenacin 7.5 mg once daily (group 3), and 31 patients were given a combination of two agents postoperatively (group 4). International prostate symptom score (IPSS) and visual analogue pain scale (VAPS) questionnaires were completed by each patient at 1st day postoperatively and on the day of stent removal.Results: In the total group of patients, the mean age was 50.24±12.90 years. There was a significant difference in the IPSS total score between group 1 and groups 3 and 4. Group 4 also differed significantly from group 1 in the irritative subscore. The obstructive subscore differed between groups 2 and 4 and group 1. There was a statistically significant difference between group 1 and group 4 in the quality of life (QoL) score.Conclusions: Combination therapy with silodosin and darifenacin improved both irritative and obstructive symptoms more than in the other groups. Combination therapy should be strongly considered for patients who complain of stent-related symptoms.

The role of antioxidant therapy in enhancing the effectiveness of assisted reproductive technology programs

Introduction. Infertility, i.e. the inability to achieve a clinical pregnancy within 12 months of a regular sexual life without contraception, is a current medical problem and affects up to 15-25% of married couples in Western countries.Objective. To evaluate the efficacy of prophylactic prescription of antioxidants in preparation for cycles of assisted reproductive technology (ART) depending on the level of anthropogenic chemicals in the patient’s body.Materials and methods. A randomized clinical trial included 144 patients with infertility who applied for ART. Prior to ART treatment, all patients were determined the level of anthropogenic chemical substances (ACS) in the blood by mass spectrometry. The concentration of the following substances was determined: mercury, cadmium, lead, and bisphenol A. The patients were divided into groups depending on the level of ACS: group 1 consisted of 72 patients with high level of ACS (5 points or more), group 2 consisted of 72 patients with low level of ACS. Antioxidant therapy in the experimental group was performed for 2 months before ART. Coenzyme Q10 300 mg/day orally, eicosapentaenoic acid 300 mg/day orally, and docosahexaenoic acid 200 mg/day orally were used as antioxidant therapy. All patients in the control group did not take antioxidant medications for at least 6 months before entering the ART cycle.Results. When evaluating the clinical outcomes of ART cycles, a positive effect of antioxidant therapy was noted in both patients with high and low levels of ACS; as a result, the chances of pregnancy were 2.3 times higher in the group of patients who received antioxidant therapy compared to the control group. The number of patients treated was 5 for both the total patient group and the subgroups depending on the level of ACS.Conclusion. The results obtained allow us to recommend the prescription of antioxidant therapy to prepare patients for ART programs.