6th Month Research Articles

Inflammatory cytokine levels and changes during omalizumab treatment in chronic spontaneous urticaria

While several studies have examined the role of T cells and related cytokines in the development of chronic spontaneous urticaria (CSU), there is a limited amount of research focusing on the changes in cytokine levels during omalizumab treatment. The primary objective of this study was to investigate the inflammatory cytokine profile (including IL-4, IL-5, IL-10, IL-13, IL-17, IL-31, IL-33, and TNFα) among CSU patients undergoing to omalizumab treatment. Plasma levels of cytokines were measured using ELISA. Measurements were taken before CSU treatment, at the 3rd and 6th months of omalizumab treatment, and once in the control group. The severity of the patients’ disease was assessed using the weekly Urticaria Activity Score(UAS7), and disease control was evaluated using the Urticaria Control Test(UCT). Thirty-one CSU patients and 56 age- and gender-matched healthy controls were included. Plasma levels of IL-4 and IL-33 were significantly lower in patients with CSU compared to healthy controls (p = 0.001; p = 0.038, respectively). During omalizumab treatment, IL-4 levels showed a significant increase in the 3rd month compared to baseline (p = 0.01), and IL-5 levels significantly decreased in the 6th month compared to both the 3rd month and baseline (6th month vs. baseline; p = 0.006, 6th month vs. 3rd month; p = 0.001). One potential mechanism of action for omalizumab may involve its regulatory effects on type 2 inflammatory cytokines in CSU patients. This finding partially explains the efficacy of anti-IL-4/13 treatments in chronic spontaneous urticaria. Further investigations on drugs targeting type 2 inflammatory cytokines in CSU are warranted.

Analysis of weight loss, metabolism, and anti-reflux effect of sleeve gastrectomy combined with fundoplication as treatment of obesity complicated by gastroesophageal reflux disease

Objective: To explore the weight-loss, metabolism, and anti-reflux effect of laparoscopic sleeve gastrectomy combined with fundoplication (SGFD) as treatment of obesity complicated by gastroesophageal reflux disease (GERD) with the aim of identifying the best treatment for such patients. Methods: This was a retrospective cohort study. Relevant clinical data of 140 patients with obesity (body mass index≥30 kg/m2) complicated by GERD (confirmed by preoperative GerdQ score, gastroscope, upper gastrointestinal radiography, 24-hour pH monitoring of esophagus, and high-resolution esophageal manometry) who had undergone bariatric surgery in the Minimally Invasive Surgery, Hernia and Abdominal Surgery Department of the People's Hospital of Xinjiang Uygur Autonomous Region from January 2019 to February 2023 were collected. The participants were allocated to the following groups according to surgical procedure performed: sleeve gastrectomy group (SG group, 92 cases) versus SGFD (SGFD group, 48 cases). SGFD, a new type of anti-reflux weight loss surgery that achieves both anti-reflux and weight loss effects by a procedure involving "cutting first and then folding", was developed by our team. In this study, our main aim was to compare and analyze differences in outcomes between the SG and SGFD groups in terms of weight loss and improvements in metabolism and reflux 3 and 6 months postoperatively. Results: The 140 patients comprised 50 men and 90 women of average age 36.0±9.6 years and preoperative body mass index (BMI) (38.5±6.5) kg/m2. The average preoperative GERD score was 10.2±1.6. There were no significant differences in baseline characteristics between the SGFD and SG groups (all P>0.05). There were also no significant differences in postoperative hospital stay, intraoperative blood loss, or postoperative complications between the two groups (all P>0.05). However, the operation time was longer in the SGFD than SG group (137.5±10.5 minutes vs. 105.3±12.6 minutes, t=-15.131, P<0.001). Compared with preoperative values, fasting blood glucose, cholesterol, body mass, BMI, and GERD score were all lower 3 months postoperatively (all P<0.05). Six months postoperatively, triglyceride, uric acid, and DeMeester score were lower in the SGFD than SG group; however, the lower esophageal sphincter resting pressure was higher in the SGFD group (all P<0.05). There were no significant differences in weight loss indexes (body mass, BMI, percentage of excess body mass loss) or metabolic indexes (fasting blood glucose, triglyceride, cholesterol, and uric acid concentrations) between the SG and SGFD groups 3 and 6 months postoperatively (all P>0.05). However, anti-reflux indexes (GerdQ score, DeMeester score, and lower esophageal sphincter resting pressure) were all significantly better in the SGFD than SG group 6 months postoperatively (all P<0.05). Conclusion: Obese patients with GERD get good weight loss, metabolism improvement and anti-reflux effect after SGFD. SGFD is a safe and feasible surgical method, and its anti-reflux effect is better than SG at the 6th month after operation, so it is feasible.

Effectiveness of inclisiran lipid-lowering therapy in patients with atherosclerotic cardiovascular disease in Moscow healthcare

Aim. To evaluate the effectiveness of PCSK9-targeted therapy (inclisiran, alirocumab, and evolocumab) in patients with atherosclerotic cardiovascular disease (ASCVD) and who did not achieve the target low-density lipoprotein cholesterol (LDL-C) level on basic therapy (statins in maximum tolerated doses and/or ezetimibe).Material and methods. This observational study included 50 patients receiving the inclisiran and 30 patients of the control group with ASCVD treated with PCSK9 inhibitors (alirocumab, n=1; evolocumab, n=29). In all participants, we assessed medical history data and initially performed electrocardiography, echocardiography, Doppler ultrasound of extracranial and lower limb arteries, and laboratory tests (complete blood count, biochemical and lipid profile). Three Moscow public health facilities took part in the study.Results. Data on achievement of primary and secondary endpoints by the 12th month are presented. The study groups were comparable in basic clinical characteristics. In inclisiran group, a significant decrease in LDL-C level was found from 2,53±0,7 mmol/l initially to 1,29±0,5 mmol/l (by 49%), p=0,0002; the target LDL-C &lt;1,4 mmol/l was achieved by 73,9% of the subjects. Alirocumab/ evolocumab showed significant lipid-lowering effect with a LDL-C decrease from 2,4±0,9 mmol/l to 1,32±0,7 mmol/l (by 45%), p&lt;0,0001.Conclusion. The final results are consistent with the intermediate data and indicate not only the possibility of early achievement of target LDL-C levels in PCSK9targeted combination therapy, but their maintenance with a favorable tolerability and safety profile.

Prospective Assessment of Glucocorticoid Toxicity in Rheumatology Practice: A Focus on the Glucocorticoid Toxicity Index.

The glucocorticoid toxicity index (GTI) is developed to measure glucocorticoid (GC)-related morbidity over time. This study aimed to assess GC-toxicity in patients at a rheumatology outpatient clinic by using the GTI and to identify the factors that interfere with the GTI. This prospective study included patients with inflammatory arthritis (IA), connective tissue disease, and vasculitis who were newly prescribed GC-treatment (GC-naive) or have been still on GC-treatment for ≤2 years (GC-experienced). Patient demographics and disease characteristics, aggregate improvement score (GTI-AIS), cumulative worsening score (GTI-CWS), and cumulative GC-doses were recorded at baseline, 3rd month, and 6th month. Generalized estimating equations (GEE) were used to evaluate the GTI scores and associated factors including cumulative GC-doses. The study included 156 (48.7% GC-naive) patients with a mean age of 49.1 ± 17.1 years. More than half of the patients in both groups had a diagnosis of vasculitis. A higher cumulative GC-dose was found to be associated with higher GTI-scores in both groups (p< 0.001). In the GC-naive group, patients with vasculitis showed higher GTI-scores than IA patients (p< 0.001); there was also a significant increase in the GTI-CWS at the 6th month compared with the 3rd month. In the GC-experienced group, GTI-AIS and GTI-CWS were significantly different at 3rd and 6th month (p< 0.05). It was shown that GTI scores were associated with cumulative GC-doses and vasculitis patients in the GC-naive patients had higher GTI scores than inflammatory arthritis. The GTI allows individualized assessment and management of adverse effects experienced by patients as a result of GC treatment.

#3115 Effectiveness of SGLT2 inhibitors in patients with glomerulonephritis: a single center experience

Abstract Background and Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become widely used in recent years because of favorable outcomes on kidney function in people with diabetes mellitus and chronic kidney disease (CKD). The main effect of SGLT2 inhibitors is inhibiting sodium and glucose reabsorption, acting precisely in the early proximal tubule of the renal nephron. Although these drugs developed as glucose-lowering agents for their capability to induce glycosuria, cardiovascular outcome studies found that the reduction in kidney function was significantly delayed, and the incidence of severe decline in kidney function was reduced in patients taking SGLT2 inhibitors. Later on, these outcomes were confirmed by the results of the DAPA-CKD, EMPA-KIDNEY, and CREDENCE studies, which were specific outcome trials in patients with CKD. However, data about the use of SGLT2 inhibitors in patients with glomerulonephritis at routine clinical practice are still limited. The purpose of this study is to investigate the impact of SGLT2 inhibitors use in patients with glomerulonephritis. Method Patients diagnosed with biopsy-proven GN who continued their routine follow-up in Etlik City Hospital nephrology clinic were retrospectively examined. Patients with a steroid treatment history for GN were excluded from this study. We identified 29 patients who were treated with SGLT2 inhibitors for proteinuria. We analyzed the baseline characteristics, comorbidities, GN types, and laboratory parameters (baseline, sixth and twelfth months at the follow-up). Each patient was matched to the control with a similar baseline feature under conservative therapy (n = 29). Both patient groups were treated in line with the KDIGO glomerulonephritis guideline and were received RAAS blockers at the maximum tolerated dose. According to baseline levels, the reduction rate in proteinuria and eGFR of the sixth and twelfth months were calculated as percentages. The study was performed in accordance with the Declaration of Helsinki. The local ethical committee approved the study design. Results Our study involved 58 patients diagnosed with 32 (55%) IgA nephropathy, 16 (28%) with membranous nephropathy, and 10 (17%) with focal segmental glomerulosclerosis. In the treatment group, 23 (79%) patients used dapagliflozin, and 6 (21%) used empagliflozin as SGLT2 inhibitors. Baseline proteinuria levels at [1940 (1780-2700 mg/d) vs. 1890 (1670-2400 mg/d); p = 0.8], eGFRs [60 (44-82) vs. 64 (46-80) ml/min/1.73 m2; p = 0.8] and serum albumin levels (39.6 ± 0.3 vs. 39.1 ± 0.2; p = 0.4) were similar between both groups. The proteinuria reduction rate in the sixth month was 34% (27.3-40.5) for the treatment group and 12% (6.9-20.7) for the control group (&amp;lt;0.0001). Besides, the reduction rate was still higher in the treatment group at the 12th month [50.5% (39-52.6) vs. 26.3% (17.2-35.4); p ≤ 0.0001]. eGFR declining rate at 6th months and 12th months were lower in SGLT2 group than the control group [3.1% (0-6.2) vs. 8.6% (4.1-16.6); p = 0.004 and 0.8% (0-5) vs. 5.9% (3.3-15.2); 0.005, respectively] (Table 1). Proteinuria levels at 6th months were 1170 (970-1890) mg/d and 1730 (1180-2100) mg/d for treatment and control group, respectively. At 12th months, median proteinuria level of SGLT2 group was 940 (840-1480) mg/d and control group was 1250 (1120- 2040) mg/d (Fig. 1). Conclusion In this study with a well-matched control group, we found that SGLT2 inhibitors demonstrate efficacy in mitigating the decline in estimated GFR and reducing albuminuria in patients with GN. However, randomized-controlled trials are still required specific to patients with GN.

#3048 Short and long term follow up of living Tunisian kidney donors

Abstract Background and Aims Over the years, concerns have increased about the harmlessness of kidney donation. This is more relevant in an Arab Muslim developing country like Tunisia, where lack of cadaveric donors is continuously leading to an increase in living donor numbers. The aim of this study is to evaluate the safety of nephrectomy as well as medical and surgical outcomes among LKDs, both short and long terms. Method Longitudinal monocentric study, involving a cohort of 106 LKDs in which nephrectomies were performed between November 2007 and April 2015. Donors that attended their follow-up visits after donation as per the European Renal Best Practice group recommendations by the European Renal Disease Association were included.10 Because of the irregularity of visits, we defined visits as follows: M1=from hospital discharge to the 3rd month, M3=from the 3rd month to 6th month, M6=from the 6th month to the 1st year, Y1=from the 1st year to 2nd year, Y2=from the 2nd year to the 4th year, and Y4=4 years and more. At the time of evaluation, we looked for the presence or history of renal events (i.e., elevation of serum creatinine level or proteinuria). We also detected by periodical check- up the presence or history of other physical or biological affections such as the presence of hypertension (HTN), diabetes mellitus (DM), sugar intolerance, hyperlipidemia, or hyper-uricemia (Table 1). Results 92 donors were included in the follow-up analysis after following exclusion criteria. The mean age at the time of nephrectomy was 42.8 ± 10 years with the sex ratio 0.6. and 27% of our donors were mothers. Twenty-two percent of the donors were obese and 4% were hypertensive. The median initial glomerular filtration rate (GFR) was 105 mL/min/1.73 m2. The surgical approach was costal lumbotomy in 96% of cases and laparoscopy for four cases. The kidneys were removed from the left side in 93% of cases. Postoperative mortality was zero and early postoperative morbidity was low. The median duration of hospital stay was nine days. During follow-up, 14% attended all recommended visits. The median follow- up duration was 26 months. After two years post donation, the prevalence of HTN was 28% and obesity was 26%. The prevalence of GFR decline (50–59 mL/min) was 14% using formula by modification of diet in renal disease. None of our donors reached stage 4 or 5 CKD. Twelve had proteinuria and one donor had diabetes, a comparable prevalence of morbidities to the general population Conclusion Our results are strong arguments for harmlessness of renal donation but emphasize the importance of a careful and science-based selection process. Post donation follow-up, seemingly insufficient in our study, is the only guarantor of short- and long-term safety for donors and therefore helps to encourage the act of donating in other potential donors.

#2926 The impact of GLP-1 receptor agonists on metabolic control and diabetic kidney disease progression

Abstract Background and Aims Diabetic kidney disease is the leading cause of end-stage kidney disease in developed world. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are a class of drugs that have shown benefits beyond glycemic control, with a reduction in cardiovascular risk and renoprotective effects. The aim of this study was to assess the effect of GLP-1 RA in metabolic control and progression of CKD. Our objective was to analyze the impact and efficacy of GLP-1 RA in patients with chronic kidney disease (CKD). Method This was a retrospective cohort study, that included type 2 diabetic patients with CKD, followed in Nephrology outpatient clinic, who started treatment with GLP-1 RA between January 2019 and February 2022. Clinical, demographic and laboratory data were collect at the initiation of the therapy, 6 months and 1 year during follow-up. Results A total of 66 patients were included, of whom 63.6% (n = 42) males with a mean age of 67.8 ± 10.9 years. 95.5% (n = 63) had history of hypertension, 59.1% (n = 39) heart failure and 16.7% (n = 11) peripheral arterial disease. The median estimated glomerular filtration rate (eGFR) at beginning of the treatment was 45 [31.8-65] mL/min/1.73 m2, mean HbA1c of 9.1 ± 1.7%, and mean weight 89.4 ± 15.4 kg. The most frequently prescribed GLP-1 RA were liraglutide (34.8%, n = 23) and dulaglutide (34.8%, n = 23), followed by semaglutide (21.2%, n = 14) and exenatide (1.5%, n = 1). Regarding concomitant therapy, all of the patients were on renin-angiotensin-aldosterone system antagonists, 90.9% (n = 60) were on SGLT2 inhibitors, and 68.2% (n = 45) were on insulin. At 6 months follow-up, there was a statistically significant reduction in HbA1c (9.2 ± 1.8 VS 7.8 ± 1.7, p &amp;lt; 0.001) and weight (89.4 ± 15.4 VS 86.8 ± 15.7, p = 0.002). There were no significant differences in eGFR, lipidic profile and albuminuria. At 1 year follow-up, there was significant reduction of HbA1c (Z = −4.6, p &amp;lt; 0.001), weight (Z = −3.1, p = 0.002), and a statistically significant increase of eGFR (49.5 ± 25.4 VS 56.9 ± 27.0, p = 0.007), with no significant differences in lipidic profile and albuminuria. During the follow-up period, 5 patients voluntarily discontinued the treatment, and 1 patient suspended it due to gastrointestinal adverse effects. Conclusion Our study findings reinforce the existing evidence supporting the renoprotective effects of GLP-1 RA. We observed a notable improvement in metabolic control, as evidenced by significant reduction of HbA1c and weight, particularly at the 6th month. There were no significant differences in albuminuria during the follow up time, but an unexpected increase in eGFR.

#1237 Management of dyslipidaemia with evolocumab in kidney transplant recipients

Abstract Background and Aims Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have shown to reduce major adverse cardiovascular events in very-high cardiovascular risk patients, even with chronic kidney disease. However, the experience is very scarce in kidney transplant (KT) recipients. Method We performed a prospective cohort study of KT recipients who started evolocumab in our hospital (15/09/22–11/05/23) and were followed during at least 6 months. The criteria for its prescription were not achieving therapeutic c-LDL goals despite high-potency statins and ezetimibe treatment or adverse effects of statins (myalgias, hypertransaminasemia). Total cholesterol, c-LDL, triglycerides, estimated glomerular filtration rate (eGFR) and albuminuria were compared at baseline, 1st, 3rd and 6th month after starting the treatment. We also collected drug-related adverse effects and immunosuppressive trough levels. Results In this period, 13 KT started evolocumab. Previous lipid-lowering treatments were maintained. Mean KT vintage was 32.4 months and 69.2% had personal history of ischemic heart disease. Median follow-up was 7 months. Mean baseline c-LDL was 102.9 mg/dL and eGFR was 49 mL/min/m2. In the 3rd month after starting the treatment, we observed a reduction in cholesterol and c-LDL (p = 0.008, p = 0.009), which was maintained at 6 months (p &amp;lt; 0.001, p = 0.002). However, no differences were found in triglycerides, eGFR, albuminuria and plasma immunosuppressants levels (Fig. 1). No cases of acute rejection or adverse effects were reported. In 5 patients, anti-HLA antibodies were determined as a part of their routine follow-up 6 months after the drug prescription and were negative. Conclusion In our experience, we observed good results with evolocumab, since total cholesterol and c-LDL reduced rapidly after starting the treatment. Furthermore, renal function maintained stable, no change in proteinuria and no other safety concerns were reported. In our case, neither tacrolimus nor everolimus trough levels remained unchanged and no immunological adverse outcomes were notified. More studies in this population and with longer follow-up are needed to assess the benefit on KT recipients and graft survival.

#2315 Impact of iron and erythropoiesis-stimulating agent dose on mortality of hemodialysis patients with cancer

Abstract Background and Aims Anemia and iron deficiencies are frequent in hemodialysis (HD) patients and in patients with cancer. If specific guidelines on the management of erythropoiesis-stimulating agent (ESA) in HD patients with cancer have been published, the association between the iron status and the risk of morbidity and mortality in this population remains elusive. Method This retrospective, observational study include HD patients who had been diagnosed with cancer after the start of HD, between September 2009 and March 2021. Demographics, lab test, iron status and cumulative dose of iron and ESA were collected quarterly, from one year before cancer diagnosis to one year after. Univariate analyses were performed to assess the impact of iron or ESA exposure on mortality, after modelling exposure before and after diagnosis of cancer. Then, each model was adjusted, using the baseline variables that were found to be independently associated with mortality. Cox proportional-hazards modelling was used for all regression analyses. P-value &amp;lt; .05 is considered significant. Results Seventy-nine patients were included, with a median follow-up of 2.2 years (IQR: 0.9–5.3). At baseline, the median age was 72 years (IQR 63–79), 30.4% were women. The median dialysis vintage before the diagnosis of cancer was 3 years (IQR 2-7). The main cancers found were prostate (14%), colorectal (13%), bronchopulmonary (11%), urothelial (10%) and skin (10%). Lymph node involvement were observed in 18% and metastasis in 16% patients. The median hemoglobin level was 10.4 g/dL (IQR 9.9–11.7), the median ferritin level was 412 ng/mL (IQR 213–626). The median cumulative quarterly dose of iron was 600 (215–900) mg and the cumulative dose of ESA was 71 (IQR 40–148) UI/kg/week of darbopoetin alfa or equivalent. The year following the cancer diagnosis, the median dose of iron administered remained stable, but with significant variations between patients. There was an increase in the median dose of ESA, particularly after the 6th month, up to 134 (35–314) UI/kg/week. The median hemoglobin remained between 10 and 12 g/dL. The median ferritin level rises moderately during the first 6 months, then returns to values equivalent to those preceding the diagnosis of cancer. Mortality after 12 months of follow-up was high (mortality rate of 47.4%). Age, the presence of a atrial fibrillation, lymphatic invasion, metastatic invasion, or the need for more than one antitumor treatment were independently associated with mortality. In adjusted analysis (using baseline characteristics associated with death), an association with all-cause mortality was only observed with the cumulative dose of ESA in the year preceding the diagnosis of cancer (HR 1.41 [1.06–1.88], P = .017). In multivariate analysis, an association was observed between all-cause mortality and the cumulative dose of ESA in the year preceding the diagnosis of cancer, with an HR of 1.37 (1.03-1.83, P = .031). This association between all-cause mortality and cumulative dose of ESA was also found in the year following cancer diagnosis, but without reaching significance (HR 1.37 [0.95-1.98], P = .092). However, there was no association between mortality and the cumulative dose of iron administered before or after the diagnosis of cancer in multivariate analyses. Conclusion In HD patients diagnosed with cancer, the amount of iron administered was not associated with an increased risk of mortality, probably making it possible to increase the doses administered, if necessary, without any additional risk. However, it was not possible to guarantee the safety of increasing the dose of ESA in these patients. These findings should be confirmed in a larger population in order to define guideline for iron and ESA supplementation in this population.

#1286 Utility of cinacalcet treatment in kidney transplant recipients with persistent hyperparathyroidism

Abstract Background and Aims Secondary hyperparathyroidism occurs in the majority of patients with chronic kidney disease (CKD). It may persist in up to 50-66% of patients despite the initial decrease in PTH levels after successful kidney transplantation (KT). Maintaining parathyroid hormone (PTH) levels within the normal range during the post-transplant period is crucial because it is related to hypercalcemia, hypophosphatemia, and reduced bone mass in KT recipients. Studies have already demonstrated that persistent hyperparathyroidism is associated with graft loss and all-cause mortality. Vitamin D, vitamin D analogs, and calcimimetics are most commonly used to manage hyperparathyroidism. However, studies about the long-term effect of calcimimetic therapy on the allograft are still limited. In this study, we aim to investigate the long-term allograft results of patients who received cinacalcet treatment for hyperparathyroidism. Method This study was conducted in Gazi University nephrology dialysis and transplantation unit with 312 patients who were transplanted between 1996 and 2019 and continued routine follow-up visits. Persistent hyperparathyroidism is defined as elevated PTH levels after the first year of KT (serum PTH&amp;gt;88 pg/mL). All patients without concurrent hypercalcemia were treated with vitamin D or analogs according to their vitamin D levels. Patients with non-functional allograft and parathyroidectomy after KT were excluded from this study. In addition, patients with rejection episodes, which could be confounding factor for allograft survival, were excluded to evaluate the isolated effect of cinacalcet on the allograft function. We identified 115 patients with persistent hyperparathyroidism, of whom were treated with cinacalcet (n = 21) or not (n = 94). We analyzed the baseline characteristics, comorbidities, and immunosuppressive treatments of the groups. Additionally, annual eGFR changes (Δ eGFR) calculated based on baseline (post-transplantation 6th month) eGFR after KT was also examined to evaluate the effect of cinacalcet on the graft. Results The mean age of the patients was 44.3 ± 12.6 years, and 47 (41%) were women. The median follow-up time of the patients was 87 (49-117) months. Twenty-nine patients (25%) underwent cadaveric transplantation, and 47 (41%) patients received anti-thymoglobulin (ATG) in induction therapy. While all patients were given glucocorticoids as maintenance immunosuppressive therapy, 93 (81%) of the patients received tacrolimus and, 9 (8%) cyclosporin as CNI, 78 (68%) received anti-metabolite therapy. Fifty-eight patients (19%) were used mTORi. A total of 21 patients with persistent hyperparathyroidism (21%) were treated with cinacalcet. Dialysis time is longer in the cinacalcet-treated group than in the patients not treated with cinacalcet (p &amp;lt; 0.001). The preemptive transplantation rate was lower (p = 0.03), and the delayed graft function was higher in the cinacalcet-treated group (p = 0.04). In the first year after KT, serum median PTH levels were 227 (167-341) pg/ml in the cinacalcet group and 110 (86-160) pg/ml in the other group, respectively (&amp;lt;0.001). Also, serum phosphate level is lower in the treatment group (2.7 ± 0.4 mg/dl vs. 3.1 ± 0.7 mg/dl, p = 0.03). At the last visit of patients, we observed similar median PTH levels between groups [141 (100-222) vs. 108 (73-159), p = 0.08]. During the follow-up, CMV episodes and BKV nephropathy diagnosis rates were similar between the groups (Table 1). Δ eGFRs in the first year (p = 0.7), second year (p = 0.2), third year (p = 0.4), and fifth year (p = 0.6) after KT were similar between both groups. Conclusion Our study suggests that cinacalcet treatment could be a safe and effective treatment for patients with persistent hyperparathyroidism. In long-term follow-up, there is no evidence of a reduction of kidney function. However, more trials are still required for other clinical outcomes such as fracture risk and cardiovascular morbidity and mortality.

#1679 Relationship between initial eGFR DIP with proteinuria after SGLT2i treatment, in patients with IgA nephropathy. A real-world clinical study

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). However, they often cause an initial decline in estimated glomerular filtration rate (eGFR). The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the initial functional dip in eGFR. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of &amp;gt;0.5 grams/day at screening were included. Patients with secondary IgAN were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Results 55 patients (38/17 M/F), with mean age of 44,2±18,3 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 66.17±19,7 ml/min/1.73 m2 and Upr: 2356±1023 mg/24H. There was a transient decline in eGFR, 30 days after initiation of dapagliflozin (66.17±19,7 min/1.73 m2 at baseline to 57 ml/min/1.73 m2) but then, there was an improvement at month 3 from baseline. The Upr/24H difference for dapagliflozin was −25.1% (95% CI −27.5, −23.2; p &amp;lt; 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs. Notably, a significant correlation was found between the initial eGFR dip and percentage proteinuria reduction in the 12th month. (R = –0.23; p = 0.03). Consistent results of dapagliflozin treatment on proteinuria were found in all analysis subgroups including sex, baseline proteinuria, systolic blood pressure, and body mass index. No hypoglycaemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy in patients with maximally tolerated RASi. Higher initial eGFR dip after treatment initiation was a predictor of a significantly higher reduction in proteinuria at the end of follow-up. The correlation between eGFR dip and proteinuria reduction perhaps reflects the intraglomerular pressure reduction, mediated by tubuloglomerular feedback, one of the numerous.

#2408 Effect of low and very low protein diet with ketoanalogue on progression of CKD, quality of life and KAP in India: an interim analysis

Abstract Background and Aims Recent studies have established lack of advantages of Very Low Protein (VLP) with Ketoanalogues in CKD progression against to the KIDGO guidelines [1]. No systematic study is available in India to examine effect of Low protein (LP) and VLP with Ketoanalogue towards CKD prevention even though there were diverse in dietary habits. Further, effect of counseling on QoL, KAP and CKD outcomes have also not been examined. Present study intended to examine effect of dietary intervention on CKD progression, QoL, and KAP. Method This ongoing prospective randomized controlled trial was initiated since December 2022. A total of 198 patients of CKD 3 to 5 (ND) of age 18 to 60 years were completed one year. Enrolled subjects were screened from Nephrology OPD for CKD diagnosis and counselling was done for dietary intake. Their basic demographic profile socio- economic status, dietary habits, physical activity and biochemical details are being recorded through which e-GFR is calculated by CKD-EPI formula at baseline. All were randomised into 3 groups- Normal protein (0.8-1.0 gm/kg/day), low protein (0.6 gm/kg/day) and very low protein supplemented with Ketoanalogues (0.3 gm/kg/day) as a method of dietary intervention. Their dietary nutrient analysis (calories, protein, sodium, potassium, and phosphorus) was done by Diet Cal version 10.0 software using a 4-day dietary record. Dietary nutrients, nutritional status (BMI, BP, pallor, MUAC and handgrip) and all other parameters were measured at baseline, at 6th and 12th month. All patients underwent dietary intervention with home-based Personalised supervision (PS) diet. Dietary re-enforcement and counselling for clinical as well as diet-related patient concerns were done by exclusive renal dietician with weekly telephone calls. KAP and QoL were also recorded at baseline and after 6 months. The parameters were analysed by using the paired t-tests and one-way ANOVA to assess Effect of PS. Results A total 198 subjects were completed one year study. The detail demography has depicted in Table 1. Among them 79% were literate and 58.6%, 34.5%, and 6.8% were Non vegetarian, vegetarians and ovo-vegetarian respectively. Of total, there were CKD 3 (NP-30, LP- 28 and VLP-33), CKD 4 (LP-31 and VLP-32) and CKD 5 (LP-16 and VLP- 27) respectively. At baseline, all three stages have low protein intake (CKD3-36.0 g, CKD 4-34.1 g and CKD 5-31.6 g) against the standard (36.6-43.3 g) in 61 kg as mean weight. Further, in normal, low and very low groups there were 36.1 g, 35.5 g and 31.0 g protein intake respectively. Intake of sodium was high and potassium was low, which has been reversed after 1 year. (p = .000). Further, there were significant improvement in most of nutritional and biochemical parameters. However, total dietary intake and calories increased but couldn't reach to the recommendations in non-dialysis patients. (Table 1) As shown in Fig. 1, the e-GFR has increases in all groups, whereas in VLP group it has decreases non- significantly at one year. Physical component score (PCS) as QoL has improved from 2389.1 ± 415.2 to 3527.2 ± 657.5 (p = .000) whereas, Mental component score (MCS) has decreased. After counselling, all the components of KAP have been improved significantly. Conclusion Interim analysis showed that at sixth month there was slowing in progression of CKD manifested by increase in e-GFR among NP, LP and VLP with Ketoanalogue group, whereas at one year, there were non- significant reduction in VLP group. After dietary counselling, both KAP and PCS have been improved significantly.

Effectiveness of bladder retraining programme on bedwetting frequency and relapse rate of children with nocturnal enuresis

Nocturnal enuresis, or bedwetting, is a prevalent and emotionally challenging condition that has a significant impact on the behavior, psychological well-being, and social lives of school-aged children. This study aimed to assess the effectiveness of bladder retraining programme on bedwetting frequency and relapse rate among children with nocturnal enuresis. The study was conducted in two phases. The Phase I included a survey questionnaire to identify the prevalence of nocturnal enuresis among school children studying in Grade I to Grade X of 3 selected schools in Nashik, India. Out of 2150 prevalence questionnaires, 1900 filled in questionnaires were received back. 226 children were found to be positive for monosymptomatic nocturnal enuresis. A total of 160 children were selected from which 80 samples were included in experimental group and 80 were in control group. A three-step bladder retraining program was provided for parents and children in the experimental group. The parents and children from experimental group were called on the 15th day to reinforce the interventions. Posttests were conducted at 1st month (Posttest I), 3rd month (Posttest II), and 6th month (Posttest III/Relapse) for both experimental and control group. The total prevalence of nocturnal enuresis among 1900 school age children aged 6 years-15 years is found to be 11.89%. Out of the 226 enuretic children, majority 101 (44.69%) wet their beds 1-3 times per week while 48 (21.23%) children wet their beds Every night. Comparison of bedwetting frequency in both groups during Pretest, Posttest I, Posttest II and Posttest III using chi-square test showed that: In pretest there was no significant difference between children in experimental and control group as indicated by the non-significant P value 0.43. Whereas in posttest I, II & III, P value 0.001 indicates highly significant difference in bedwetting frequency of children in both the groups. Children in experimental group had a relapse rate of 3.75% and 100% relapse was observed in control group during posttest III (at 6th month). The study findings revealed a statistically significant reduction in bedwetting frequency within the experimental group (p=0.001), contrasting with the control group's non-significant change (p=0.17). Additionally, the relapse rate was markedly lower in the experimental group (3.75%) compared to the control group (100%). This aligns with Garcia-Fernandez and Petros' (2020) findings, where a squatting-based pelvic floor rehabilitation method demonstrated a significant reduction in bedwetting frequency, curing 86% of children. Van Kampen etal.'s (2009) study also supported the efficacy of pelvic floor muscle training in reducing relapse rates, providing further validation for the current study's findings. The 3 step bladder retraining programme was found to be very effective in reducing the bedwetting frequency and relapse rate among children. This study provides evidence supporting effectiveness of such tailored bladder retraining interventions in managing monosymptomatic nocturnal enuresis in school-aged children.

Pyogenic granuloma of maxillary median gingiva in a pediatric patient: A case report and literature review

Pyogenic granuloma (PG) is a painless pedunculated granulomatous lesion that develops on the skin and mucous membranes. PG in children is relatively rare. We herein report a case of PG of the maxillary median gingiva in a pediatric patient. The patient was a 6-year-old Japanese boy who presented with a painless mass with bleeding after exfoliation of the left upper deciduous central incisor. The lesion had undergone continuous, rapid growth for approximately 10 days. Intraoral findings revealed a painless, elastic, soft, and non-pedunculated mass, measuring 15 &amp;times; 10 mm, in the left upper deciduous central incisor area. To differentiate it from malignancy, an excisional biopsy was performed on the patient under general anesthesia. Histological findings confirmed that the patient suffered from PG. At the time of writing this paper, the patient had been clinically followed up for the 18th month after the surgery, showing no signs of tumor recurrence.

Four Patients with Neonatal Diabetes Mellitus and their Outcomes: A Case Series

Background: Neonatal diabetes mellitus (NDM) is a severe type of glucose metabolism disorder that appears in the first months of life and mostly presents with symptoms such as dehydration, inability to gain weight, and in extreme cases, ketoacidosis and coma. Strong evidence shows the benefits of early molecular tests that investigate variability in kATP channels such as KCNJ11, ABCC8, INS gene mutations, and 6q24 abnormalities. In the presence of these genomics changes, switching from Insulin treatment toward high-dose oral sulfonylurea can enhance the course of treatment, prognosis, and quality of life. Case Report: In this study, we report four cases of neonatal diabetes with different symptoms who were referred to Shahid Sadoughi Medical Center in Yazd, Iran. Conclusion: The diagnosis and treatment of NDM is a good model for implementing patient-centered and personalized medicine. For all patients with diabetes diagnosed before the 6th month of their age (even the 12th month), genetic testing should be considered.

IgG and IgM responses to the Plasmodium falciparum asexual stage antigens reflect respectively protection against malaria during pregnancy and infanthood.

Plasmodium falciparum malaria is a public health issue mostly seen in tropical countries. Until now, there is no effective malaria vaccine against antigens specific to the blood-stage of P. falciparum infection. Because the pathogenesis of malarial disease results from blood-stage infection, it is essential to identify the most promising blood-stage vaccine candidate antigens under natural exposure to malaria infection. A cohort of 400 pregnant women and their infants was implemented in South Benin. An active and passive protocol of malaria surveillance was established during pregnancy and infancy to precisely ascertain malaria infections during the follow-up. Twenty-eight antibody (Ab) responses specific to seven malaria candidate vaccine antigens were repeatedly quantified during pregnancy (3 time points) and infancy (6 time points) in order to study the Ab kinetics and their protective role. Abs were quantified by ELISA and logistic, linear and cox-proportional hazard model were performed to analyse the associations between Ab responses and protection against malaria in mothers and infants, taking into account socio-economic factors and for infants an environmental risk of exposure. The levels of IgM against MSP1, MSP2 and MSP3 showed an early protective response against the onset of symptomatic malaria infections starting from the 18th month of life, whereas no association was found for IgG responses during infancy. In women, some IgG responses tend to be associated with a protection against malaria risk along pregnancy and at delivery, among them IgG3 against GLURP-R0 and IgG2 against MSP1. The main finding suggests that IgM should be considered in vaccine designs during infanthood. Investigation of the functional role played by IgM in malaria protection needs further attention.

Inulin supplementation exhibits increased muscle mass via gut-muscle axis in children with obesity: double evidence from clinical and in vitro studies.

Gut microbiota manipulation may reverse metabolic abnormalities in obesity. Our previous studies demonstrated that inulin supplementation significantly promoted Bifidobacterium and fat-free mass in obese children. We aimed to study gut-muscle axis from inulin supplementation in these children. In clinical phase, the plasma samples from 46 participants aged 7-15years, were analyzed for muscle biomarkers before and after 6-month inulin supplementation. In parallel, the plausible mechanism of muscle production via gut-muscle axis was examined using macrophage cell line. Bifidobacterium was cultured in semi-refined medium with inulin used in the clinical phase. Cell-free supernatant was collected and used in lipopolysaccharide (LPS)-induced macrophage cell line to determine inflammatory and anti-inflammatory gene expression. In clinical phase, IL-15 and creatinine/cystatin C ratio significantly increased from baseline to the 6th month. In vitro study showed that metabolites derived from Bifidobacterium capable of utilizing inulin contained the abundance of SCFAs. In the presence of LPS, treatment from Bifidobacterium + inulin downregulated TNF-α, IL-6, IL-1β, and iNOS, but upregulated FIZZ-1 and TGF-β expression. Inulin supplementation promoted the muscle biomarkers in agreement with fat-free mass gain, elucidating by Bifidobacterium metabolites derived from inulin digestion showed in vitro anti-inflammatory activity and decreased systemic pro-inflammation, thus promoting muscle production via gut-muscle axis response.Clinical Trial Registry number: NCT03968003.

Preconception depression reduces fertility: a couple-based prospective preconception cohort.

Is preconception depression associated with time to pregnancy (TTP) and infertility? Couples with preconception depression needed a longer time to become pregnant and exhibited an increased risk of infertility. Preconception depression in women contributes to impaired fertility in clinical populations. However, evidence from the general population-especially based on couples-is relatively scant. A couple-based prospective preconception cohort study was performed in 16 premarital examination centers between April 2019 and June 2021. The final analysis included 16521 couples who tried to conceive for ≤6 months at enrollment. Patients with infertility were defined as those with a TTP ≥12 months and those who conceived through ART. Couples' depression was assessed using the Patient Health Questionnaire-9 at baseline. Reproductive outcomes were obtained via telephone at 6 and 12 months after enrollment. Fertility odds ratios (FORs) and infertility risk ratios (RRs) in different preconception depression groups were analyzed using the Cox proportional-hazard models and logistic regression, respectively. Of the 16 521 couples analyzed, 10834 (65.6%) and 746 (4.5%) couples achieved pregnancy within the first 6 months and between the 6th and 12th months, respectively. The median (P25, P75) TTP was 3.0 (2.0, 6.0) months. The infertility rate was 13.01%. After adjusting for potential confounders, in the individual-specific analyses, we found that preconception depression in women was significantly related to reduced odds of fertility (FOR = 0.947, 95% CI: 0.908-0.988), and preconception depression in either men or women was associated with an increased risk of infertility (women: RR = 1.212, 95% CI: 1.076-1.366; men: RR = 1.214, 95% CI: 1.068-1.381); in the couple-based analyses, we found that-compared to couples where neither partner had depression-the couples where both partners had depression exhibited reduced fertility (adjusted FOR = 0.904, 95% CI: 0.838-0.975). The risk of infertility in the group where only the woman had depression and both partners had depression increased by 17.8% (RR = 1.178, 95% CI: 1.026-1.353) and 46.9% (RR = 1.469, 95% CI: 1.203-1.793), respectively. Reporting and recall bias were unavoidable in this large epidemiological study. Some residual confounding factors-such as the use of anti-depressants and other medications, sexual habits, and prior depressive and anxiety symptoms-remain unaddressed. We used a cut-off score of 5 to define depression, which is lower than prior studies. Finally, we assessed depression only at baseline, therefore we could not detect effects of temporal changes in depression on fertility. This couple-based study indicated that preconception depression in individuals and couples negatively impacts couples' fertility. Early detection and intervention of depression to improve fertility should focus on both sexes. This work was supported by grants from the National Natural Science Foundation of China (No. 82273638) and the National Key Research and Development Program of China (No. 2018YFC1004201). All authors declare no conflicts of interest. N/A.

Bioeconomics of juvenile seahorse (Hippocampus erectus) culture: Optimal harvest time

AbstractThe culture of seahorses Hippocampus erectus in captivity represents a window of opportunity for the diversification of the aquaculture activity in the ornamental industry. In this study, we have constructed a bioeconomic model to evaluate the optimal harvest time (OHT) over a culture period of 562 days. The bioeconomic model was integrated with three submodels: biological, technological, and economic. Three different mortality rates were used for different periods in culture, registering a higher survival in the period from 0 to 60 days with a rate of 53.4%. The sensitivity analysis showed that the mortality rate in this period was the parameter with the greatest influence on the benefits. The Von Bertalanffy growth model was indicated to describe the growth of H. erectus given its statistical significance using Theil's inequality coefficient, registering parameters of (L∞ = 141.62 mm) and (k = 0.0049 month‐1). The bioeconomic model determined the OHT in the 4th month of culture, the time when the maximum profit is recorded. It is concluded that the culture presents challenges to be addressed although the bioeconomic model allows for demonstrating the OHT.

Visual outcome of cataract surgery in paediatric uveitis

1. To analyse the visual outcome in patients of paediatric uveitis who underwent cataract surgery; 2. To analyse the post-operative complications of cataract surgery in paediatric uveitis.Retrospective observational study was done on patients of uveitis who underwent cataract surgery. Patients who were under 18 years and co-operative for examination were included.They underwent Phacoaspiration with posterior chamber IOL implantation by a single surgeon after 3 months of activity free interval, BCVA(in Log MAR) in every follow up, anterior segment examination using slit lamp and posterior segment examination using IDO, post-operative complications and Intra ocular pressure was recorded using Noncontact tonometer.Uveitis was classified using the SUN classification of uveitis. Use of corticosteroids, biologics and immunosuppressive drug were collected at each visit. Total of 18 subjects diagnosed with cataract as a complication of uveitis &amp; undergone cataract surgery were studied (6 were females, 12 were males) 9 had anterior uveitis, 1had intermediate uveitis and 5 had pan uveitis. JRA (66.7%) was the most common cause identified. Improvement in vision from baseline was observed post-surgery at the end of first, third and 6th month which was statistically significant (P- Value &amp;#60;0.05). Average duration of disease before they underwent surgery was 18 months. Most common post op complication was posterior capsular opacification (50 %), others include secondary glaucoma (38.9), exudative retinal detachment (5.6%) and Vitritis (22.2%)Unlike adult uveitic patients, the surgical management of paediatric uveitic cataract is both challenging and controversial, and the surgery itself has been associated with poor visual outcomes. However, our study had shown that with implantation of IOL, good immunosuppressants and control of the disease can give these children a good visual outcome.