Istanbul Bilim University

The functional connectivity (FC) of the amygdala in Alzheimer’s disease (AD) and its relationship to cognitive impairment is still not well established. Thus, we examined resting-state FC changes in the amygdala among 21 patients with AD dementia (ADD) and 34 individuals with amnestic mild cognitive impairment (aMCI), compared to 33 individuals with subjective cognitive impairment (SCI), to provide insights into the association between amygdala FC and cognitive decline in different clinical stages of Alzheimer’s disease. We conducted seed-to-voxel FC analysis, focused on two cognitive functions, episodic memory, and face recognition, and examined the correlations between changes in FC of the amygdala and cognitive test scores. We demonstrated that the left amygdala exhibits progressive disruption in FC, especially with the frontal regions in aMCI and ADD. We further identified that this disrupted FC in the left amygdala showed significant positive correlations with cognitive test scores from the MCI stage onward. Our results indicate that FC changes in the left amygdala may serve as an early marker of AD and this FC pattern of amygdala influence detrimentally affects episodic memory and face recognition functions. These findings highlight that the amygdala may be a critical anatomical region for detecting the early stages of AD.

Background Transaldolase deficiency (TALDO) is a rare autosomal recessive disorder of the pentose phosphate pathway, presenting with end‐stage liver disease, renal tubular dysfunction, and coagulopathies. Liver transplantation has emerged as a potential treatment for end‐stage liver disease in TALDO patients, though clinical evidence is limited to seven reported cases. Methods We describe the case of a pediatric patient with TALDO who successfully underwent living donor liver transplantation. Clinical, preoperative, surgical, and postoperative data were reviewed and compared with previously reported cases. Results A 3‐year 4‐month‐old girl with TALDO presented with end‐stage liver disease, recurrent bleeding, and suspected hepatocellular carcinoma (HCC). She received a left lateral segment graft from her father. Postoperatively, coagulopathy and bleeding episodes resolved, with stable liver function at 1 year. Histopathology revealed cirrhosis without HCC. Complications included bile duct stenosis, successfully managed. Conclusions This case emphasizes liver transplantation as a lifesaving option for TALDO patients with end‐stage liver disease. While short‐term outcomes are promising, further studies are needed to evaluate long‐term prognosis and growth outcomes. Reporting additional cases is vital to refine management strategies.

Objective To assess the effectiveness of COVID-19 vaccination in patients with rheumatic diseases undergoing biologic (bDMARDs) or targeted-synthetic disease-modifying anti-rheumatic drugs (tsDMARDs). Methods This cross-sectional study was conducted at ten rheumatology clinics in Turkey between May 1, 2021, and October 30, 2022. Patients with rheumatic diseases on bDMARD or tsDMARD therapy who received at least two doses of an mRNA or inactivated SARS-CoV-2 vaccine were included. After vaccination, COVID-19 infection rates, adverse events, and rheumatic disease flares were recorded. Data were collected via face-to-face or telephone interviews. Results A total of 963 participants were included in the final analysis; 44% were male, and the median age was 49 years. The most frequently observed rheumatic diseases were ankylosing spondylitis and rheumatoid arthritis, accounting for 37.2% and 32.6% of cases, respectively. Adalimumab (19.2%) and infliximab (17.8%) were the most commonly used bDMARDs. Of the participants, 634 (65.9%) received an inactivated vaccine (CoronaVac) and 329 (34.1%) an mRNA vaccine (BioNTech). A total of 502 (52.1%) patients received a booster dose. Following the first, second, and third vaccine doses, adverse event rates were 19.9%, 15.9%, and 26.7%, respectively. Forty-two (4.4%) patients experienced a disease flare within six months after their first vaccination dose. COVID-19 infection occurred in 79 participants (8.2%) after two vaccine doses; most cases were symptomatic but did not require hospitalization. The COVID-19 infection rate was lower in participants who received a booster dose than those who did not (3.4% vs . 8.2%, P <0.001). Conclusions Our study indicates that both mRNA and inactivated SARS-CoV-2 vaccines are effective in preventing severe COVID-19 outcomes, with an acceptable rate of adverse events and disease flares among patients with rheumatic diseases on bDMARD or tsDMARD therapy.

It is well known that aging affects many systems in the body. The digestive system is one of the systems most affected by aging. In our study, we examined the effects of young plasma treatment on cell proliferation, growth factors, immune defense and histological parameters in the jejunum of aged male rats. For this purpose, aged male Sprague Dawley rats (24 months, n = 7) were treated with pooled plasma (0.5 ml/day, intravenously for 30 days) collected from young (5 weeks, n = 51) rats. Aged rats that received young plasma treatment were grouped as the experimental group, while aged rats formed the control group. At the end of the experiment, the jejunums of the groups were collected and histological parameters such as villus height, crypt depth, total mucosal thickness and surface absorption areas were measured and compared. In addition, cell proliferation index and proliferation intensity in the crypt glands of the jejunum were evaluated with proliferating cell nuclear antigen and expressions of growth factors such as insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) expression and effects of immunoglobulin A (IgA), which plays a role in the defense of the digestive system against microorganisms, were examined. In the experimental group, an increase in histological parameters, IGF-R and IGF-IR expression, proliferation density, proliferation index and IgA expression density and IgA cell count were observed compared to the control group. These results suggest that young plasma treatment has a positive effect on the digestive system and may be a potential therapeutic for tissue regeneration.

Objectives: We aim to assess whether severely frail patients have an increased risk of complications and worse surgical outcomes after retrograde intrarenal surgery. Methods: The data of 340 consecutive patients undergoing retrograde intrarenal surgery to treat upper tract urinary stones were analyzed retrospectively. The 5-item modified frailty index (mFI-5) was used to assess the frailty status. Using a cutoff value of score 2 in the mFI-5 score, patients were divided into two groups: patients with an mFI-5 score <2 were assigned to a non-frail (Group 1) group, and patients with an mFI-5 score ≥2 were assigned to a frail (Group 2) group. The patients' demographics, stone characteristics, operative outcomes, and complication rates were compared between the groups. The primary objective was to examine whether the surgical outcomes were much better in non-frail patients. Results: After matching confounding factors, Group 1 comprised 255 patients, and Group 2 comprised 85 patients. The baseline characteristics were similar between the groups. There were no statistically significant differences in terms of the median operation time and length of hospital stay among groups. There were no significant differences between groups for intraoperative complication rates (7.6% and 9.4%, respectively; P = .47) and postoperative complication rates (13.8% and 11.8%, respectively; P = .71), and stone-free rates (70.9% versus 72.9%, respectively; P = .73). Conclusions: Retrograde intrarenal surgery is an efficient and feasible treatment option for upper urinary tract stones in severely frail patients.

Background Diabetic neuropathy (DN) is a heterogeneous condition characterized by complex pathophysiological changes affecting both autonomic and somatic components of the nervous system. Inflammation and oxidative stress are recognized contributors to the pathogenesis of DN. This study aims to evaluate the therapeutic potential of dichloroacetic acid (DCA) in alleviating DN symptoms, focusing on its anti-inflammatory and antioxidant properties. Methods Thirty-two adult male Sprague Dawley rats were divided into four groups: Control, Diabetic, and two DCA-treated groups receiving 5 mg/kg and 10 mg/kg of DCA, respectively. Diabetes was induced with streptozotocin (STZ) injections. Assessments included lipid peroxidation levels, plasma fibroblast growth factor-21 (FGF-21) and transforming growth factor-beta (TGF-β) levels, electrophysiological measurements, histological examination of the sciatic nerve, and motor function tests. Results Treatment with DCA significantly reduced malondialdehyde (MDA) levels, indicating decreased lipid peroxidation. Plasma TGF-β levels were also lower in the DCA-treated groups, suggesting diminished inflammation. Conversely, plasma FGF-21 levels were elevated. Electrophysiological assessments revealed enhanced compound muscle action potential (CMAP) amplitudes and reduced distal latencies in DCA-treated rats, indicative of improved nerve conduction. Histopathological examinations showed reduced perineural thickness in the sciatic nerves of DCA-treated rats, pointing to decreased fibrosis. Enhanced performance in motor function tests was observed in these rats, implying improved muscle strength and motor capacity. Conclusions The study demonstrates that DCA therapy significantly reduces oxidative stress and inflammation in a rat model of DN, thereby ameliorating neuropathic symptoms. These results support the potential of DCA as a promising therapeutic agent for DN treatment. Further research is warranted to explore its clinical applications and to provide more detailed insights.

This review examines the inconsistent effects of endocrine-disrupting chemicals (EDCs) and pollutants on pubertal timing, emphasizing the methodological challenges contributing to variability in findings. Data from nine key studies reveal that chemicals such as BPA, phthalates, and PFAS impact pubertal onset differently based on exposure timing, dosage, and sex. For instance, BPA is linked to earlier puberty in girls but delayed onset in boys, while other EDCs show mixed effects across populations. These discrepancies often arise from challenges in study design, such as the difficulty in establishing reliable control groups, accurately measuring exposures, and accounting for confounding factors like socioeconomic status, diet, and obesity. Sex-specific differences and environmental shifts during the COVID-19 pandemic, including increased indoor exposure and stress, further complicate the picture. These factors highlight the urgent need for more robust research methodologies, including standardized exposure assessments and longitudinal studies, to clarify the mechanisms driving these effects. Despite these challenges, the findings stress the importance of public health interventions, such as stricter EDC regulations, improved pollutant monitoring, and minimizing exposures during sensitive developmental windows. Addressing methodological gaps is crucial for producing reliable, actionable insights to protect adolescent development from the adverse effects of EDCs.

Objective The objective of this study is to evaluate whether adding oral glucocorticoids to immunosuppressive therapy improves skin scores and ensures safety in patients with early diffuse cutaneous systemic sclerosis (dcSSc). Methods We performed an emulated randomized trial comparing the changes from baseline to 12 ± 3 months of the modified Rodnan skin score (mRSS: primary outcome) in patients with early dcSSc receiving either oral glucocorticoids (≤20 mg/day prednisone equivalent) combined with immunosuppression (treated) or immunosuppression alone (controls), using data from the European Scleroderma Trials and Research Group. Secondary end points were the difference occurrence of progressive skin or lung fibrosis and scleroderma renal crisis. Matching propensity score was used to adjust for baseline imbalance between groups. Results We matched 208 patients (mean age 49 years; 33% male; 59% anti‐Scl70), 104 in each treatment group, obtaining comparable characteristics at baseline. In the treated group, patients received a median prednisone dose of 5 mg/day. Mean mRSS change at 12 ± 3 months was similar in the two groups (decrease of 2.7 [95% confidence interval {95% CI} 1.4–4.0] in treated vs 3.1 [95% CI 1.9–4.4] in control, P = 0.64). Similar results were observed in patients with shorter disease duration (≤ 24 months) or with mRSS ≤22. There was no between‐group difference for all prespecified secondary outcomes. A case of scleroderma renal crisis occurred in both groups. Conclusion We did not find any significant benefit of adding low‐dose oral glucocorticoids to immunosuppression for skin fibrosis, and at this dosage, glucocorticoid did not increase the risk of scleroderma renal crisis.

Objectives HSD3B7 deficiency is a genetic disorder caused by mutations in the HSD3B7 gene, leading to impaired bile acid synthesis and the accumulation of toxic intermediates. Affected patients typically present with cholestatic liver disease, including jaundice and progressive liver dysfunction. Case presentation This case series describes three pediatric patients from two families diagnosed with HSD3B7 deficiency, each demonstrating varying clinical severity and outcomes. All cases exhibited cholestasis with normal GGT levels and elevated AST/ALT. Case 1, a male infant, also presented with craniosynostosis and failure to thrive, responding well to cholic acid therapy. Case 2, a female infant and first cousin of Case 1, had mild cardiac abnormalities and showed slight improvement with ursodeoxycholic acid and vitamin supplementation. Case 3, a male infant with a compound HSD3B7 and ATP8B1 mutation, progressed to fulminant liver failure, ultimately requiring a liver transplant. A novel c.531 + 1G>C variant was identified in Cases 1 and 2, contributing to understanding genotype–phenotype correlations in bile acid synthesis disorders. Conclusions Early diagnosis and treatment with bile acid therapy are crucial for improving outcomes, although some cases may necessitate liver transplantation. This series emphasizes the need to consider bile acid synthesis disorders in the differential diagnosis of cholestasis.

Objectives The aim of this study was to determine the effects of a training program based on educational brochures and audio recordings of testicular cancer (TC) stories on testicular self‐examination (TSE) and health beliefs among university students. Design The study had a pretest–posttest, control group experimental design. Sample This study was conducted with 106 students in Turkey. Method Data were collected using a personal information form, the Health Beliefs Model (HBM) Scale for TC and TSE, and a form for determining TSE and sharing information. Results There was a statistically significant difference between the posttest scores obtained by the intervention group, who received the training and the control group on the susceptibility, benefits and health motivation, barriers, self‐efficacy, and health motivation dimensions of the HBM Scale ( p < 0.05). The percentage of TSE in the intervention group increased from 14.8% to 90.7% after receiving training on TC and TSE, which was significantly different from the pretest and posttest scores of the control group. Conclusions Training using educational brochures and audio recordings of TC stories had a positive effect on TSE and health beliefs. The results suggest that both training methods can be used to increase social awareness of TC.

Background: Recombinant growth hormone (rhGH) has been used since 1985 to treat growth hormone (GH)-induced short stature, typically associated with transient adverse events. However, lipoatrophy, characterized by irreversible damage to subcutaneous fat, was first reported in 1999 and linked to antibody formation. In 2021, localized lipoatrophy was observed in 14.5% of patients receiving daily rhGH, with repeated injections at the same sites being a common contributing factor. Long-acting rhGH (LAGH) preparation offers the advantage of weekly injections, enhancing patient comfort and adherence to treatment. Methods: This case report discusses a 5.5-year-old girl born at 40 weeks of gestation with a birth weight of 2300 g, diagnosed with idiopathic short stature and borderline GH secretion, along with a history of mild intrauterine growth retardation. Results: After initiating treatment with the non-pegylated fusion protein formulation of LAGH at the standard dose of 0.66 mg/kg body weight weekly, administered by her family, she developed localized lipoatrophy at the injection site within eleven weeks. The injections were performed consistently in the same area of the right upper arm, where lipoatrophy emerged. Following the onset of this adverse effect, her treatment was adjusted to daily rhGH, with strict instructions to rotate injection sites. Despite these clear instructions, follow-up revealed that the parents continued to administer injections with the non-pegylated LAGH fusion protein formulation, this time in the left upper arm, leading to a recurrence of lipoatrophy within eight weeks. Conclusions: The recurrence underscores the importance of proper injection techniques, particularly site rotation, in preventing localized adverse effects. Given the limitations of this case, where the recommended adjustments were not followed by the parents, it is crucial to emphasize that the administration of the preparation should be discontinued immediately upon the appearance of side effects such as lipoatrophy. Individual reactions to drugs are always possible, and this highlights the need for clinician vigilance in monitoring and addressing adverse effects promptly during treatments with LAGH.

Purpose Postoperative fever (POF)/urinary tract infection (UTI) is one of the most unpleasant and undesirable conditions for surgeons after retrograde intrarenal surgery (RIRS). RIRS is not recommended for any patient with a positive urine culture to avoid POF and UTI, but some patients may develop postoperative UTI even if the urine culture is sterile. This study investigated the predictive factors of fever and UTIs after RIRS. Methods In total, 1240 patients who underwent RIRS for proximal ureteral stones and/or kidney stones were analyzed. After case-control matching, 168 patients were included in the study. Demographic data, preoperative/peroperative/postoperative data, and hematological parameters were compared. Patients with sterile urine cultures were included in the study. Postoperative fever was defined as fever ≥ 38 °C within 72 h after RIRS. Patients were divided into two groups: those with and without POF/UTI. Demographic data, preoperative and postoperative findings, and inflammatory parameters of the patients were compared retrospectively. Results POF/UTI was observed in 61 (36.3%) of 168 patients who underwent RIRS. After case-control matching, increased body mass index (BMI) and longer operation time were found to be significant predictors of POF/UTI (p = 0.001 and 0.016 respectively). Preoperative systemic immune-inflammation index (SII) (PxN/L), high Platelet/Lymphocyte Ratio (PLR), and urine leukocyte positivity were found to be significant predictors of POF/UTI (p = 0.037, 0.025 and 0.038 respectively). Conclusion Hematological parameters are simple and feasible to use to evaluate POF/UTI in patients undergoing RIRS. High SII and PLR may predict POF and early infection after RIRS. In addition, according to demographic data and per-operative status, high BMI and prolonged operation time are risk factors for infection.

Importance Increasing evidence supports the oncologic safety of de-escalating axillary surgery for patients with breast cancer after neoadjuvant chemotherapy (NAC). Objective To evaluate the oncologic outcomes of de-escalating axillary surgery among patients with clinically node (cN)–positive breast cancer and patients whose disease became cN negative after NAC (ycN negative). Design, Setting, and Participants In the NEOSENTITURK MF-1803 prospective cohort registry trial, patients from 37 centers with cT1-4N1-3M0 disease treated with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) alone or with ypN-negative or ypN-positive disease after NAC were recruited between February 15, 2019, and January 1, 2023, and evaluated. Exposure Treatment with SLNB or TAD after NAC. Main Outcomes and Measures The primary aim of the study was axillary, locoregional, or distant recurrence rates; disease-free survival; and disease-specific survival. Number of axillary lymph nodes removed was also evaluated. Results A total of 976 patients (median age, 46 years [range, 21-80 years]) with cT1-4N1-3M0 disease underwent SLNB (n = 620) or TAD alone (n = 356). Most of the cohort had a mapping procedure with blue dye alone (645 [66.1%]) with (n = 177) or without (n = 468) TAD. Overall, no difference was found between patients treated with TAD and patients treated with SLNB in the median number of total lymph nodes removed (TAD, 4 [3-6] vs SLNB, 4 [3-6]; P = .09). Among patients with ypN-positive disease, those who underwent TAD were more likely to have a lower median lymph node ratio (TAD, 0.28 [IQR, 0.20-0.40] vs SLNB, 0.33 [IQR, 0.20-0.50]; P = .03). At a median follow-up of 39 months (IQR, 29-48 months), no significant difference was found in the rates of ipsilateral axillary recurrence (0.3% [1 of 356] vs 0.3% [2 of 620]; P ≥ .99) or locoregional recurrence (0.6% [2 of 356] vs 1.1% [7 of 620]; P = .50) between the TAD and SLNB groups, with an overall locoregional recurrence rate of 0.9% (9 of 976). The initial clinical tumor stage, pathologic complete response, and use of blue dye alone as a mapping procedure were not associated with the outcome. Even though patients with TAD demonstrated an increased disease-free survival rate compared with the SLNB group, this difference did not reach statistical significance (94.9% vs 92.6%; P = .07). Factors associated with decreased 5-year disease-specific survival were cN2-3 axillary stage (cN1, 98.7% vs cN2-3, 96.8%; P = .03) and nonluminal type tumor pathologic characteristics (luminal, 98.9% vs nonluminal, 96.9%; P = .007). Conclusions and Relevance The short-term results suggest very low rates of axillary and locoregional recurrence in a select group of patients with cN-negative disease after NAC treated with TAD alone or SLNB alone followed by regional nodal irradiation regardless of the SLNB technique or nodal pathology. Whether TAD might provide a clear survival advantage compared with SLNB remains to be proven in studies with longer follow-up.

Objective(s) In our study, the neuroprotective efficacy of pre- and post-traumatic applications of boric acid (BA) in rats with experimentally induced spinal cord injury (SCI) was investigated. Materials and Methods The experimental animals were divided into four groups: control group (C), SCI group (SCI), BA-treated group before SCI (BA+SCI), and BA-treated group after SCI (SCI+BA). Forty-eight hours after SCI, biochemical levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and cytochrome c (Cytc) and caspase-3 (Casp3) expressions were measured in the spinal cord tissues and were examined histologically. Results After SCI, oxidative stress markers, such as MDA, TOS, and OSI, and apoptosis markers Cytc and Casp3 showed an increase in levels compared to Group C. The oxidative stress markers that increased after SCI decreased with BA+SCI application, while Cytc level, one of the apoptosis markers that increased after SCI, decreased in both groups with BA application. Cell, myelin, ependymal damage, and hemorrhage levels increased after SCI compared to Group C. These histological markers increased after SCI and decreased after BA+SCI. BA was found to reduce SCI-induced oxidative stress and oxidative stress-induced apoptosis. Conclusion BA administered before SCI was shown to be more effective in protecting neural damage.

Purpose In cardiovascular surgeries, iron deficiency anemia and transfusion of blood products are associated with mortality and morbidity, prolonged hospital stay and poor patient outcomes. Patient blood management (PBM) is a patient-centered approach based on a ‘three pillar’ model that promotes optimum use of blood and blood products to improve outcomes. This study assessed the potential budget impact of implementing PBM in patients undergoing elective cardiovascular surgery in a private hospital in Turkey. Methods Two models were developed to estimate the hospital budget impact of PBM. The first model encompassed implementation of the first pillar of PBM, which proposes treatment of iron deficiency anemia before a surgical procedure. The second covered implementation of all three pillars of PBM. Budget impact was estimated from the number of avoided complications after treating iron deficiency anemia and reducing blood transfusions. Rates of complication (sepsis, myocardial infarction, renal failure and stroke) with and without PBM were taken from published meta-analyses. Data on 882 cardiovascular operations performed during 2020–2022 were taken from the Florence Nightingale Istanbul Hospital. The costs of treating complications were estimated by applying Turkish Social Security Institution prices to a healthcare resource utilization tool for each complication completed by experts. Results Results from the budget impact analysis showed that, by implementing the first pillar of PBM, the department could have avoided 30 complications and saved 4,189,802 TRY. For the second model based on implementing all three pillars of PBM, 29 complications could have been avoided by reducing the number of transfusions, with budget savings of 6,174,434 TRY. Reducing the length of hospital stay could have enabled 137 additional operations in the given period. Conclusion Implementation of PBM in patients undergoing elective cardiovascular surgery in private hospitals could be a budget-saving strategy in Turkey and may provide an opportunity to increase revenue.

Very-long-chain fatty acids (VLCFAs) are commonly used to diagnose peroxisomal disorders, but elevated levels may also result from other non-peroxisomal causes, leading to diagnostic challenges. We report the case of a 2-year-old girl presenting with growth retardation and diarrhea, with laboratory investigations revealing elevated VLCFA levels suggestive of a peroxisomal disorder. Despite initial suspicion, genetic panels for peroxisomal and dyslipidemia-associated genes were negative. Whole exome sequencing (WES) ultimately revealed a pathogenic variant in the ABCG8 gene, consistent with a diagnosis of sitosterolemia, a rare autosomal recessive condition characterized by elevated plant sterols. Elevated plant sterols in sitosterolemia may interfere with VLCFA analysis, potentially leading to falsely elevated results and incorrect suspicion of peroxisomal dysfunction. This case underscores the importance of including sitosterolemia in the differential diagnosis for elevated VLCFA levels, particularly in patients with atypical presentations for peroxisomal disorders. It also highlights the role of WES in establishing an accurate diagnosis when biochemical findings are ambiguous. More studies are needed to evaluate the effects of plant sterols on VLCFA measurements. This report contributes to the literature by demonstrating the utility of genetic testing in clarifying challenging diagnostic scenarios involving elevated VLCFAs.