Sixth Month Research Articles

Kinetics of Lymphocytosis during First-Line Treatment with BTK Covalent Inhibitors in Chronic Lymphocytic Leukemia Patients: An Italian Multicenter Experience of Real Life

CONCLUSIONS In chronic lymphocytic leukemia (CLL) patients (pts) the first phase of treatment with covalent Bruton's tyrosine kinase inhibitors (cBTKi), Ibrutinib or Acalabrutinib, is characterized by an increased absolute lymphocyte count (ALC), regardless of previous lines of treatment. Ibrutinib, as first-line therapy, induces lymphocytosis in about 57% of pts, and it is more prominent in IGHV mutated CLL patients. This phenomenon, due to the spread of neoplastic lymphocytes from the nodal compartment into peripheral blood, is transient in most patients, resolving within 8 months, but can rarely persist over 12 months, without any impact on survival: the criterion of Partial Response with Lymphocytosis (PR-L) was introduced for this phenomenon. Despite lymphocytosis in Ibrutinib has been widely investigated, little is known about the effective presence, kinetics and duration of lymphocytosis in patients treated with Acalabrutinib. The main purpose of this multicentric study was to define, in a real-life setting, the kinetics of drug-induced lymphocytosis in CLL patients treated with Acalabrutinib or Ibrutinib, in order to discover any possible differences in terms of entity and duration of this phenomenon. In our multicentric retrospective study we enrolled 204 pts (127 male and 77 female), treated in first line with cBTKi (136 Ibrutinib and 68 Acalabrutinib), from 16 different Italian centers, between April 2016 and November 2022, with last follow up in April 2023. For each patient we collected data about the burden of disease at baseline (in terms of staging, lymph nodes involvement, presence of splenomegaly), and about the biological features of the disease (cytogenetic aberrations and molecular mutations, IGHV status). Then we evaluated the ALC at the baseline and at well-defined time-points (after two weeks, 1, 2, 3, 6, 9, 12 months) over an observation period of 1 year. Patients' characteristics are reported in Figure 1. The main differences between the two groups were observed in FISH and molecular biology, with a prevalence of del17p and mutated TP53 among Ibrutinib-treated patients. We observed a median ALC increase after the beginning of therapy in both groups. Median lymphocytosis was higher than baseline during the first month of treatment in both cohorts. A progressive decline in median ALC occurred from the second month of treatment in both groups: at this time-point, median lymphocyte count was 62% of baseline in Acalabrutinib cohort versus 84% in Ibrutinib cohort (p=0.025). From the sixth month to the end of the study we found a statistical difference in the ALC with higher counts in the Ibrutinib group. In fact, at this time point, median ALC was 6960/microL in Acalabrutinib compared to 11010/microL in Ibrutinib group (13% vs 30% of baseline), at the ninth month it was 4550/microL vs 8230/microL (10% vs 20% of baseline) and after twelve months it was 2740/microL vs 5520/microL (8% vs 13% compared to baseline) in the Acalabrutinib versus Ibrutinib group, respectively. Besides, we evaluated the percentage of lymphocytosis resolution in both arms at different timepoints and we observed a quicker restoration of an ALC < 5000/mmc in the Acalabrutinib arm. The results are illustrated in Figure 1. Acalabrutinib seems to determine, like Ibrutinib, an increase of ALC immediately after the starting of treatment. Therefore, lymphocytosis appears as a cBTKi-class effect. Despite this, the kinetics of lymphocytosis are not overlapping in the two groups: since the sixth month of therapy ALC reaches almost-normal values in the Acalabrutinib group, with significant statistical differences compared to Ibrutinib. These data suggest that lymphocytosis seems to be less long-lasting in patients treated with Acalabrutinib than in those ones treated with Ibrutinib and the response criterion of PR-L may have a less scope for applicability during treatment with Acalabrutinib.

The mechanism and kinetics of antianginal effect formation after laser therapy course in patients with angina pectoris

Purpose: To assess some mechanisms of antianginal effect formation under low-level infrared laser irradiation in patients with angina pectoris, as well as to clarify the kinetics of this clinical effect after laser therapy course. Materials and methods. 88 male patients, aged 54.2 ± 3.7, with angina pectoris of functional class II–III were examined. 63 patients of the main group had a ten-day course of laser therapy. 25 patients were included in the control group in which laser irradiation was only simulated. At the initial stage and one month after laser therapy or its imitation, and in the main group additionally after 3 and 6 months, bicycle ergometric tests were performed to determine exercise tolerance and evaluate the double product indicator at the level of initial (P1) and maximum (P2) threshold load, if its threshold power exceeded the initial one. Results and discussion. The increase of exercise tolerance was observed in 79.5 % of patients from the main group one month later and in 81.7 % three months later after finishing laser therapy course, with the increase in exercise tolerance by 19.1 W (+ 30.4 %; p = 0.023) and by 22.7 W (36.2 %; p = 0.009), respectively. The antianginal effect lasted for about 6 months of follow-up in 62.0 % of treated patients. The double product indicator reflecting myocardial oxygen consumption at P1 level after laser irradiation had a pronounced downward trend. This indicator increased at maximum load (P2) by 19.1 % (p = 0.04) and by 24.1 % (p = 0.006) during repeated examinations in 1 and 3 months, respectively. By the sixth month of observation, studied parameters returned to the initial levels. There were no statistically significant changes in the studied parameters in patients from the control group. Conclusion. The data obtained indicate that a ten-day course of laser therapy triggers high and long-lasting antianginal effect in patients with angina pectoris. The mechanism of its action is caused with the economization factor of cardiac activity and with the increase of coronary blood flow productivity.

In Vivo Effects of Porcine and Rabbit Antithymocyte Globulin in Patients with Severe Aplastic Anemia

Background: Severeaplastic anemia (SAA) is a bone marrow failure disorder mediated by T lymphocytes, resulting in severe deficiency of hematopoietic stem cells. Horse antithymocyte globulin (H-ATG) plus cyclosporin was the first-line therapy for SAA patients in the absence of an HLA-matched sibling 1. The inhibitory effect of Rabbit-ATG (R-ATG) on lymphocytes is more deeply than that of H-ATG, and the recovery of CD4 T cells is slower, resulting in poor efficacy in SAA patients 2. Porcine ATG (P-ATG) and R-ATG are two available immunosuppressive choices in China mainland, the first-line formulation of ATG remains unknown. Methods: From November 2020 through September 2022, we performed a prospective, multi-center, non-randomized trial comparing two ATG formulations. 15 patients received R-ATG therapy and 45 patients treated with P-ATG were collected by prospective registration (ChiCTR2200055696) in the Chinese Eastern Collaboration Group of Anemia (CECGA). The pharmacokinetics, dynamic changes of peripheral blood cells were evaluated. Hematologic responses were also evaluated at 3, 6 months after treatment. Results: In both P-ATG-treated and R-ATG-treated patients, ATG reached highest concentration 5 days after treatment (1268.4 ± 381.1 ug/ml and 641.2 ± 448.5 ug/ml for P-ATG and R-ATG, respectively), and gradually decreased. At week 2, week 3 and 1 month from the peak values when be assessed, the P-ATG concentration decreased by 70.3%, 81.7%, and 85.4%, while the R-ATG concentration decreased by 68.9%, 88.5%, and 92.2%, respectively. R-ATG showed more powerful effects in depleting peripheral blood lymphocytes than P-ATG, while P-ATG displayed rapid recovery of T cells (CD3 + T cells, CD4 + T cells and CD8 + T cells) (P-ATG vs R-ATG, CD3 + T cells: 30.18 ± 6.04% vs 0.49 ± 0.37%, p=0.0036; 60.58 ± 8.02% vs 7.16 ± 7.16%, p=0.0016; 77.83 ± 3.17% vs 59.67 ± 7.93%, p= 0.015 for day 3, week 1 and week 3, respectively; CD4 + T cells: 9.13 ± 2.20% vs 0.03 ± 0.02%, p=0.013, 24.49 ± 4.21% vs 1.75 ± 1.75%, p=0.0076; 38.49 ± 3.02% vs 17.62 ± 3.79%, p=0.0007 for day 3, week 1 and week 3, respectively; CD8 + T cells: 16.77 ± 4.15 vs 0.10 ± 0.067, p=0.015; 27.55 ± 3.56% vs 4.94 ± 4.94%, p=0.0036; 33.80 ± 2.19% vs 35.67 ± 6.20, p=0.72 for day 3, week 1 and week 3, respectively). There were lower number of neutrophils in patients treated with R-ATG than those treated with P-ATG during the first week after immunosuppressive therapy (P-ATG vs R-ATG, Day 3: 3.46 ± 0.49 vs 1.29 ± 0.56, p=0.02; Day 5: 3.73 ± 0.56 vs 1.12 ± 0.55, p=0.02). The overall response rates were comparable between P-ATG and R-ATG at third month and sixth month (60% vs 40%, p=0.24; 60% vs 60%, p=1). Early infection rates (within 1 month) showed no significant differences in two formulations (P-ATG vs R-ATG, 33.33% vs 46.67%, p=0.76). There were five deaths in patients treated with P-ATG and three deaths in R-ATG-treated patients (P-ATG vs R-ATG, 11.1% vs 20.0%, p=0.40). Conclusion: P-ATG and R-ATG showed different pharmacokinetics and effects on neutrophils, lymphocyte subsets, which may lead to diverse immunosuppression. These two kinds of globulins showed comparable overall response rate after treatment. Reference 1. Scheinberg P, Nunez O, Weinstein B, et al. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011;365(5):430-438. 2. Feng X, Scheinberg P, Biancotto A, et al. In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia. Haematologica. 2014;99(9):1433-1440.

The best method for erection function in urethroplasty; is excision and primary anastomosis or buccal mucosal graft urethroplasty?

IntroductionThe aim of this study is to evaluate and compare erection function (EF) after Excision and Primary Anastomosis Urethroplasty (EPAU) and Buccal Mucosal Graft Urethroplasty (BMGU) in bulbar urethral stricture. MethodsPatients who underwent urethroplasty were identified retrospectively. The criteria for inclusion in the study were determined as being over 18 years old and under 70 years old, being sexually active. Exclusion criteria are; preoperative severe erectile dysfunction, stricture outside the bulbar urethra, psychosocial incompatibility, urethral stricture related to pelvic fracture, follow-up time less than a year. As the primary endpoint, the International Index of Erectile Function-5 (IIEF-5) was determined as a comparison of EF in the preoperative and third, sixth and twelfth months after surgery. The secondary endpoint was the evaluation of the effects of demographic data, stricture and treatment characteristics on EF. ResultsFifty patients were identified considering the inclusion/exclusion criteria. It was observed that there were 30 patients who underwent EPAU and 20 patients who underwent BMGU. At the third month after surgery, EF showed a statistically significant decrease in the EPAU group. In both patient groups, it was observed that the early negative effects after the operation in EF started to improve in the sixth month and returned to the baseline level by the first year. ConclusionEPAU and BMGU techniques have a similar effect on EF in the medium and long term. Both methods can be used safely and effectively in the appropriate patient group.

Expression of Ki67 and CD68+ cells of red bone marrow monocyte sprout under triptorelin administration in the hypothalamic-pituitary-testis regulatory system: the experimental study

Background. Red bone marrow (RBM) is the main organ of human haemopoiesis. Monocytopoiesis plays an important role in the formation of transitional states: from normal to pathology and in the transformation of pathological processes from one stage to another. In modern urological practice, the substance triptorelin is widely used for androgen deprivation therapy, according to the recommendations of the European Association of Urology. Ki67, a commercially available monoclonal antibody that reacts with a nuclear antigen detected only in proliferating cells, is used to assess immunohistochemical changes. CD68 is a valuable cytochemical marker for immunostaining of monocytes/macrophages during histochemical analysis of tissues in inflammation, cancer and other immunohistopathological purposes. The purpose of the study is to evaluate the proliferative activity and differentiation of progenitor cells through the expression of Ki67 and CD68+ monocyte sprouting of RBM under chemical castration of central origin in male rats caused by the administration of triptorelin solution with quercetin addition to the diet for one year. Materials and methods. The study was conducted on 60 adult male white rats. They were divided into 3 groups: group I — control (n = 10), group II (n = 25) — subcutaneous injection of triptorelin, group III (n = 25) — subcutaneous injection of triptorelin acetate and quercetin. Immunohistochemical analysis of biopsy specimens was conducted following a standard protocol at the Department of Pathological Anatomy in Sumy State University, under the supervision of the Head of the Department, Prof. Romaniuk A.M. Results. The study evaluated Ki67 expression on microsections of rat red bone marrow through immunohistochemistry, which exclusively reacted with nuclear antigen in the monocyte sprout’s proliferating cells. Irregular changes were revealed depending on the experimental groups and time periods. Immunohistochemical analysis of RBM tissue using anti-CD68 antibodies in the experimental groups revealed a strong positive cytoplasmic response in monocytes and resident macrophages located in the monocyte sprout and surrounding environment. The data of the two experimental groups of RBM had a noticeable proliferating compartment, as evidenced by the high content of mitotically active DNA in them. These data correspond to the results obtained in the experiment with triptorelin, where we found a marked positivity of Ki67, depending on the timing of the experiment and the addition of the flavonoid quercetin. This discrepancy suggests that bone marrow cells that grow and proliferate under normal conditions are guided by natural control mechanisms and may lose their Ki67 expression after leaving the progenitor compartment and entering the differentiation compartment. Conclusions. Triptorelin administration induces hormonal imbalance in the hypothalamus-pituitary-testis-RBM system, resulting in quantitative and qualitative alterations in the cells of the RBM monocytic lineage. The level of cell proliferation, as measured by Ki67, is highest during the third month of observation. Cytoplasmic expression of CD68 is evident in two experimental groups from the third to the sixth month, suggesting activation of immunoreactive cells as they migrate from the progenitor compartment to the differentiation compartment.

Comparison of efficacy of azilsartan with olmesartan in patients of hypertension: randomized controlled trial

Background: Azilsartan and olmesartan are members of ARBs, used in the management of hypertension. Objective was to evaluate efficacy of azilsartan with olmesartan in patients of hypertension. Methods: A randomized, prospective, open label, comparative study was carried out in Pharmacology and Medicine department at Dr. RPGMC Kangra at Tanda, HP. The study stretched over one year and blood pressure was monitored at first, third and sixth month. Out of 69 patients, 35 patients in group A were prescribed tablet azilsartan 40 mg/day and 34 patients in group B patients were prescribed tablet olmesartan 20 mg/day. Tablet chlorthalidone 12.5 mg/day was add on in both the groups. Data was presented as mean+SD. Student’s t test was used and p value <0.05 was considered significant. Results: In group A, systolic blood pressure (SBP) values improved from baseline of 153±10 mmHg to 111±18 mmHg (p<0.001) at 3 months and 109±6.1 mmHg (p<0.001) at 6 months and diastolic blood pressure (DBP) values from baseline of 87±7 mmHg to 67.1±4.6 mmHg (p<0.001) at 3 months and 67.6±2.5 mmHg (p < 0.001) at 6 months. In group B, SBP values improved from baseline of 154±8.5 mmHg to 127±3.6 mmHg (p<0.001) at 3 months and 123±4 mmHg (p<0.001) at 6 months and DBP values from baseline of 85±6.5mm Hg to 75.7±3.3 mmHg (p<0.001) at 3 months and 73±3.3 mmHg (p<0.001) at 6 months. On intergroup comparison improvement in hypertension was better in azilsartan group (p<0.001). Conclusions: The study concluded that azilsartan is significantly better than olmesartan in controlling the hypertension.

Association of Asthma With Patients Diagnosed With Metabolic Syndrome: A Cohort Study in a Tertiary Care Hospital.

Introduction Asthma is defined as a chronic inflammatory airway disease. The prevalence of both asthma and obesity has been rising simultaneously, demonstrating a parallel trend. Obesity is a significant factor in metabolic syndrome, and numerous studies have indicated a connection between metabolic syndrome and bronchial asthma. Aims and objectives The aim of this paper is to evaluate the association of asthma with patients diagnosed with metabolic syndrome. The main objectives were to analyze the clinical profile and spirometric indices in patients with metabolic syndrome and to assess asthmatic patients among them with spirometry and clinical parameters at a tertiary care hospital in Chennai. Materials and methods This hospital-based cohort study was conducted on 73 patients attending the outpatient department who had a known case of metabolic syndrome and were evaluated for asthma through history, physical examination, and a pulmonary function test. A history of cough, expectoration, shortness of breath, wheezing, chest tightness, allergy, seasonal variation, and smoking habits was asked, and a thorough physical examination was performed. Bronchial asthma was confirmed with airflow reversibility by spirometry as per the Global Initiative for Asthma Guidelines. Metabolic and spirometry parameters were examined, such as body mass index (BMI), waist circumference, waist-hip ratio, fasting blood sugar (FBS), postprandial blood sugar, hemoglobin A1C (HbA1C), serum insulin, lipid profile, C-reactive protein (CRP), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC pre- and post-reversibility (baseline vs. six months). Results and discussion The average BMI of all participants was 29.6511 ±2.64564. The waist-hip ratio was 0.5512 ±0.43855, which decreased during the follow-ups, demonstrating a decline in the risk of obesity in study participants. The level of HbA1C showed a drop from 6.1% to 5.9% at the first follow-up. This exhibited a further reduction at the six-month follow-up in addition to a positive reflection in insulin sensitivity, indicating successful control of diabetes among study participants. It was discovered that this was statistically significant (p<0.001). At the third and sixth months of follow-up, the FEV1/FVC ratio increased by 38% and 37%, respectively, when metabolic syndrome was under control. The results show that controlling diabetes, hypertension, obesity, and triglyceride values improved asthmatic symptoms, and this was determined to be statistically significant (p<0.001). Conclusion The results of the current study demonstrated that the regulation and maintenance of metabolic parameters such as BMI, diabetes, hyperlipidemia, and hypertension aid in improving asthma control.

Plasma Rich in Growth Factors (PRGF) in the Treatment of Patients With Chronic Cervical and Lumbar Pain: A Prospective Observational Clinical Study

BACKGROUND: Chronic back pain is a long-lasting disorder, whose main source of pain is often the intervertebral disc that undergoes a degenerative process associated with low-grade inflammation, leading to a reduced quality of life. OBJECTIVES: The aim of our study was to assess the efficacy of intradiscal and epidural injections of plasma rich in growth factors (PRGF) in patients with chronic clinical symptoms due to intervertebral disc (IVD) degeneration. STUDY DESIGN: Prospective observational study. SETTING: A single spine unit in a private clinic. METHODS: Thirty-two patients with cervical and lumbar chronic pain due to IVD degeneration were treated with 2 or 3 series of intradiscal and epidural PRGF infiltrations with 2 weeks between each procedure. The procedures were performed under fluoroscopic guidance and grade 3 sedation in an operating theater. Treatment efficacy was evaluated using the Spine Tango Core Outcome Measure Index questionnaire, Numeric Rating Scale for back pain, and the Oswestry Disability Index questionnaire. In addition, the number of patients who successfully achieved the minimal clinically important change was also determined. These assessments were evaluated at pretreatment (baseline) and at one, 3, and 6 months posttreatment. RESULTS: The Oswestry Disability Index, COMI Spine Tango Core Outcome Measure Index total score, and Numeric Rating Scale showed a statistically significant reduction from the baseline level to the posttreatment first month, third month, and sixth month (P &lt; 0.001). Moreover, 78.1% of the patients reached a pain reduction superior to 30% one month posttreatment, and 87.5% at 6 months posttreatment, which is considered as a clinically significant improvement. LIMITATIONS: This study was prospective and did not have a control group. Only patient-reported outcomes were evaluated. CONCLUSIONS: This observational, prospective study of patients with chronic back pain showed that 2-3 intradiscal and epidural injections of PRGF significantly decreased pain and disability at one month posttreatment and this improvement was maintained, and in some patients even improved, at 3, and 6 months posttreatment. KEY WORDS: Platelet-rich plasma, plasma rich in growth factors, degenerative disc disease, intervertebral disc degeneration, back pain, growth factors, regenerative medicine

Evaluation of Mothers’ Sociodemographic Characteristics and Infant Feeding Attitudes During Pregnancy According to the Iowa Feeding Attitude Scale and Examining the Scale’s Role in Determining Breastfeeding Duration

Introduction: The World Health Organization recommends exclusive breastfeeding for the initial 6 months of life, followed by the introduction of supplementary foods together with breast milk after 6 months, and then continuing to breastfeed until the child reaches 2 years of age. Iowa Infant Feeding Attitude Scale (IIFAS) was developed to identify which infant feeding methods pregnant women are more inclined towards during the early stages of pregnancy. In our study, we aimed to assess the feeding practices of mothers using the IIFAS. Material and methods: The study was planned with consenting pregnant women who applied to the gynaecology clinic, pregnancy outpatient clinic and pediatric outpatient clinic of our hospital. Those who had problems such as drug use, chronic disease, psychological disorder, anatomical disorder that would prevent breastfeeding, syndromic condition, indication for hospitalisation were excluded from the study. A questionnaire regarding the demographic profile of the mothers and the IIFAS was filled out. Subsequently, face-to-face interviews were conducted with the mothers on the seventh day, third month, and sixth month to gather information. Results: The study was completed with 96 mothers. According to the IOWA infant feeding scale scores of the mothers, there were 26 (27.1%) mothers in the breastfeeding-prone group with a score of 70 and above and 70 (72.9%) mothers in the undecided group with a score between 49-69. Since none of the pregnant women scored between 17-48, the group predisposed to formula feeding was not formed. There were no significant variations observed between the groups with regard to age, family type, and mode of delivery; however, there was a notable disparity in the educational and informational statuses of the mothers. Conclusions: The fact that mothers were mostly undecided about the recommendations related to the IIFAS indicates the need for information about breast milk.

Real-Life Experience With Bictegravir/Emtricitabine/Tenofovir Alafenamide in Turkey.

Single-tablet regimens (STRs) can increase treatment success and even improve the quality of life of human immunodeficiency virus (HIV) patients. In this study, we aim to analyze the real-life efficacy and tolerability data of people living with HIV (PLWH) initiated on or switched to bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF)as first-line treatment. This retrospective analysis was performed in HIV-1-positive patients who were initiated BIC/FTC/TAF in the HIV clinic between June 2020 and June 2022. Patients who received BIC/FTC/TAF for at least 12 months were included in this study. Virological suppression, laboratory parameters, side effects, and immunological response were analyzed at one, three, six, nine, and 12 months. A total of 116 patients, 66 (56.9%) treatment-experienced and 50 (43.1%) naive, were evaluated within the scope of the study. In the naive patient group, baseline HIV-RNA, CD4+ and CD8+ T cell counts, CD4/CD8 ratio, and estimated glomerular filtration rate (eGFR) values weresignificantly different in different follow-up months. The number of patients with HIV-1 RNA levels below 50 copies/mL was 55.9% in the first month, 73.7% in the third month, 90.2% in the sixth month, and 100% in the ninth and 12th months. In our real-life observational study, BIC/FTC/TAF treatment achieved rapid viral suppression, maintained viral suppression in virally suppressed patients, and was effective for immunological recovery in both treatment-experienced and naive HIV patients. No serious side effects were observed. Our study has proved the potential of BIC/FTC/TAF as an important option in the treatment of HIV patients.

Longitudinal estimates of resting energy expenditure using predictive equations in individuals with excess weight after weight loss: A systematic review with meta-analysis

To determine which resting energy expenditure (REE) predictive equation has the lowest bias in the aggregate level in individuals with excess weight during weight loss interventions. Searches were performed in MEDLINE, Web of Science, Scopus, CENTRAL and gray literature databases. Longitudinal studies on weight loss interventions which evaluated REE by predictive equations compared to that measured by indirect calorimetry in adults with excess weight at different follow-up times were included. Meta-analyses were performed with the differences between biases of predictive equations of the REE at the different follow-up times of weight loss. Of the total of 2178 occurrences found in the databases, only eight studies were included. The Harris-Benedict (1919) equation showed the smallest differences between bias up to the third month (MD=103.33kcal; 95%CI=-39.01; 245.67), in the sixth month (MD=59.16kcal; 95%CI=8.74; 109.57) and at the 12th month (MD=-71.41kcal; 95%CI=-150.38; 7.55) of weight loss follow-up. Weight loss does not seem to have an effect on bias at different follow-up times. Harris-Benedict (1919) equation seems to be the most adequate to assess the REE of individuals with excess weight during weight loss. However, the finding of large estimated predictive intervals may indicate that predictive equations may not be handy tools for individuals losing and regaining weight due to changes other than body weight.

Comparison of Apathy and Cognitive Symptoms in Pre- and Postoperative Period in Deep Brain Stimulation Surgery.

The aim of the study was to investigatie apathy and cognitive functions in Parkinson's disease patients who underwent deep brain stimulation surgery on bilateral subthalamic nuclei. This study included 18 patients with Parkinson's disease who were accommodated in the Parkinson's and Movement Disorders Center of Adana City Training and Research Hospital for treatment in 2022. Patients were evaluated by psychiatry, neurology and neurosurgery specialists with a multidisciplinary approach and found to be surgically appropriate. Standardized Mini-Mental Test and Montreal Cognitive Assessment Scale, Apathy Evaluation Scale, and Hamilton Anxiety and Depression Scale were administered to each patient before the operation and at 6 months after effective stimulation parameters were reached. The mean apathy score at the preoperative zeroth month was 47.77 ± 15.83 in patients having deep brain stimulation surgery and 30.83 ± 13.59 in the postoperative sixth month. Statistically that reduction was significant (P = .003) and showed clinical development. The average Hamilton Anxiety Scale scores at the preoperative zeroth month was 11.50 ± 5.14 and 10.22 ± 5.57 at the postoperative sixth month, with no clinical significance (P = .280). The determined value for the Unified Parkinson's Disease Rating Scale, on treatment, was 22.55 ± 7.53 in the preoperative zeroth month and 14.50 ± 6.99 in the postoperative sixth month, with statistical significance (P < .001). The Unified Parkinson's Disease Rating Scale, off treatment, score was revealed to be significant in the preoperative zeroth month (37.44 ± 9.85) in comparison to that of the postoperative sixth month (23.44 ± 7.86; P < .001). This study showed that bilateral subthalamic stimulation improves nonmotor and motor symptoms in patients having Parkinson's disease. The mechanism is complex, and we believe that future studies focusing on pharmacological and nonpharmacological treatments involving more patient groups will be useful for clinicians.

The Effect of Holder Pasteurization and Different Variants on Breast Milk Antioxidants.

After birth, breast milk (BM) is a known essential source of antioxidants for infants. We analyzed the non-enzymatic total antioxidant capacity (TAC), oxygen radical absorbance capacity (ORAC), and glutathione, calcium, transferrin, and total protein levels of human breast milk before and after Holder pasteurization (HoP). The collected donor BM samples were pasteurized with HoP. HoP decreased TAC (-12.6%), ORAC (-12.1%), transferrin (-98.3%), and total protein (-21.4%) levels; HoP did not influence the glutathione concentration, and it increased the total calcium (+25.5%) concentration. Mothers who gave birth via Cesarean section had significantly lower TAC in their BM. TAC and glutathione levels were elevated in the BM of mothers over the age of 30. BM produced in the summer had higher glutathione and calcium levels compared to BM produced in the winter. The glutathione concentration in term milk samples was significantly higher in the first two months of lactation compared to the period between the third and sixth months. The transferrin level of BM for female infants was significantly higher than the BM for boys, and mothers with a BMI above 30 had increased transferrin in their samples. Antioxidant levels in human milk are influenced by numerous factors. Environmental and maternal factors, the postpartum age at breast milk collection, and Holder pasteurization of the milk influence the antioxidant intake of the infant.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18–70 Years; A Randomized, Double-Blind Clinical Trial

BackgroundThis study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. MethodIn a randomized, double-blind, placebo-controlled trial, adults aged 18–70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. ResultBetween May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02–6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. ConclusionRCP vaccine is safe and creates strong and durable humoral and cellular immunity. Trial registration(IRCT20201214049709N2).

Neonatal cholestasis as the onset symptom of McCune-Albright syndrome: case reports and a literature review.

This study aimed to summarize and show the characteristics and evolutionary process of neonatal cholestasis caused by McCune-Albright syndrome (MAS), as neonatal cholestasis may be the initial manifestation of MAS before other classic clinical features appear. The clinical characteristics, treatment methods, and outcomes of three neonatal cholestasis cases caused by MAS in our center were retrospectively studied. In addition, all the reported cases of MAS combined with cholestasis were reviewed and summarized to show the cholestatic features in them. We have confirmed three MAS cases in our center, presenting onset symptoms of jaundice, pale stool, and neonatal cholestasis soon after birth. The cholestasis subsided spontaneously at around the sixth month. The literature review showed that the levels of total bilirubin, conjugated bilirubin, ALT, AST, and GGT in neonatal MAS cholestasis cases were 207 μmol/L (range 65-445 μmol/L), 162 μmol/L (range 46-412 μmol/L), 821 U/L (range 85-3,597 U/L), 532 U/L (range 127-3,633 U/L), and 244 U/L (range 79-3,800 U/L), respectively. Liver histology showed canalicular and hepatocellular cholestasis, giant hepatic cell transformation, and bile paucity. Extrahepatic manifestations such as café-au-lait pigmented skin lesions, Cushing's syndrome, hyperthyroidism, renal tubular dysfunction, and skeletal abnormalities could occur simultaneously when jaundice occurred. GNAS mutations had a high positive rate (83.3%-100%) in liver tissue with cholestasis. Neonatal cholestasis caused by MAS could be self-resolved, but hepatic lesions persist and have malignant potential. MAS can be one of the causes of neonatal cholestasis, which may be the first manifestation of the disease. Extrahepatic coexisting symptoms of MAS and liver histology can help to distinguish MAS from other etiology of cholestasis. Detecting GNAS mutations in liver tissue may shorten diagnostic time and is of particular interest in the partial and atypical forms of MAS with neonatal cholestasis. Neonatal cholestasis in children with MAS can self-resolve, but liver dysfunction and malignant lesions persist.

Main Portal Vein Diameter Changes in Patients Undergoing Gastric Surgery for Malignancy: An Observational CT Study

Abstract Background In the follow-up computed tomography (CT) examinations of patients who had undergone gastrectomy for gastric malignancy in our center, we noticed by chance that there was an isolated increase in the diameter of the main portal vein (MPV) without other radiological findings of portal hypertension. Objectives In this study, we aimed to evaluate whether the MPV diameter of patients who had gastric surgery for malignancy differed in the preoperative and postoperative periods and its change over time in patients who underwent postoperative follow-up examinations. Materials and Methods The CT images of 240 patients who underwent abdomen CT for staging and follow-up gastric malignancy between January 2017 and September 2021 were evaluated retrospectively. The CT scans of the remaining 149 patients after the exclusion criteria were included in the study. All CT imaging was performed using multidetector CT (64 or 128 slice) in portal venous phases. The images were evaluated by two radiologists based on consensus. Maximum MPV diameter were measured outer wall to outer wall with calipers on axial images at the level of 1 cm distal to the portosplenic confluence. Results One hundred forty-nine patients included in the study had preoperative CT examination. Eighty-three patients had follow-up CT examination at third month, 89 patients at sixth month, and 99 patients at first year. The MPV diameters differed significantly between preoperative CT and postoperative third month, sixth month, and first year CT (p = 0.001, p = 0.001, and p = 0.001, respectively). There was no difference in MPV diameter between postoperative third month CT and postoperative 6th month and 1st year CT (p = 0.514 and p = 0.078, respectively). Conclusion There is an increase in MPV diameter in the first 3 months postoperatively in patients undergoing gastric surgery for malignancy. This enlargement continues unchanged in the first 1 year follow-up. The radiologists' awareness of this situation may prevent the wrong diagnosis of portal hypertension, unnecessary concern, and further investigation.

Nasal Tip Flexibility and Stability: Comparison of Septal Extension Grafts and Columellar Strut Grafts in a Prospective Trial.

The stability of nasal tip rotation and projection, and providing a flexible nasal tip, are important elements in rhinoplasty. Two common options to provide these requirements are the septal extension graft (SEG) and the columellar strut graft (CSG). This study aims to compare nasal tip stability and flexibility between the 2 graft options. A prospective randomized study was carried out in 60 patients operated on with either the CSG or the SEG. Tip rotation and projection stability were analyzed with photographic evaluation at the immediate postoperative period, the first month, and the first year. Nasal tip flexibility was evaluated with a newton meter at the preoperative period and postoperative first, third, and sixth months and the first year. The CSG showed a significant loss of projection and rotation, whereas the SEG showed better preservation of projection and rotation. However, both options showed a greater loss of projection and rotation in the first month and then a slight decrease in the following months. Although the SEG had lesser flexibility compared with the CSG anteroposteriorly, there was no flexibility difference between them in the lateral direction in the long term. The SEG provides better nasal tip stability compared with the CSG. The greatest downside of the SEG is decreased flexibility compared with the CSG. Surgeons should be aware of the loss of projection and rotation with both graft options and adjust their operation plan according to these points. Therapeutic, II.

THE RELATIONSHIP BETWEEN INITIAL CLINICAL FINDINGS AND RENAL INVOLVEMENT OF HENOCH SCHÖNLEIN PURPURA IN PEDIATRIC PATIENTS

OBJECTIVE: Henoch-Schönlein purpura (HSP) is an IgA-associated systemic vasculitis characterized by three important clinical signs of non-thrombocytopenic palpable purpura, abdominal pain, and arthritis. Renal involvement generally determines the prognosis. In this study, it was aimed to determine the relationship between skin, gastrointestinal system (GIS), the severity of joint and renal involvement on the clinical features of children who were followed up with the diagnosis of HSP. MATERIAL AND METHODS: In this prospective cross-sectional study, 74 pediatric patients followed up between January 2011 and January 2012 were evaluated with their history, physical examination, laboratory measurements, treatment received during follow-up, and response to treatment. System involvement of the patients was classified as skin, renal, GIS, and joint involvement. RESULTS: It was determined that 45.9% of the cases were female and 54.1% were male. A significant correlation was found between the severity of arthritis and renal involvement in the first month (p&amp;lt;0.05). There was a significant correlation between the severity of abdominal pain and renal involvement at the time of admission, and also the severity of abdominal pain and severity of renal involvement at the sixth month (p&amp;lt;0.05). A significant correlation was found between the response of abdominal pain to painkillers and renal involvement in the first month (p&amp;lt;0.05). CONCLUSIONS: Severe joint and GIS involvement at the beginning of the disease and severe GIS involvement at the beginning were found to be associated with severe renal involvement in the first and sixth months. Patients who initially had severe abdominal pain, and therefore could not move at all, fall behind from the game, prefer to lie down continuously, and/or those with melena should be evaluated more carefully in terms of renal involvement.

A pilot study on the relationship between thrombospondin-1 (THBS1) and transforming growth factor beta1 (TGFβ1) in the bovine placenta during early mid-pregnancy as well as parturition with normally released and retained placenta.

During pregnancy, it is necessary to create appropriate conditions for the development of the placenta and the fetus. However, during parturition, the placenta must be separated and subsequently removed as soon as possible to not expose the female to the possibility of infection. In this study, the relationship between thrombospondin-1(THBS1)and transforming growth factor beta1(TGFβ1) concentrations was described during bovine pregnancy (second, fourth, and sixth months; n = 3/each month), at normal parturition (NR) and parturition with fetal membrane retention (R). The presence of THBS1 and TGFβ1 was confirmed in bovine placental tissues of both maternal and fetal parts. Enzyme-linked immunosorbent assay showedstatistically significant differences (p < 0.05) in THBS1 concentrations (pg/mg protein) between examined parturient samples (maternal part: 5.76 ± 1.61 in R vs. 2.26 ± 1.58 in NR; fetal part: 2.62 ± 1.94 in R vs. 1.70 ± 0.23 in NR). TGFβ1 concentrations (pg/mg protein) were significantly lower (p < 0.05) in the retained fetal membranes compared to the released fetal membranes in the maternal part of the placenta (26.22 ± 7.53 in NR vs. 17.80 ± 5.01 in R). The participation of THBS1 in the activation of TGFβ1 in parturient bovine placental tissues leading to the normal release of fetal membranes may be suggested.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

BackgroundPrimary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor.Case presentationThe proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband’s daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient’s blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father’s first signs of brown tumor were in the right maxilla, while the daughter’s appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland.ConclusionWe report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.