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Background/aim: Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting synovial joints, often causing to joint destruction and systemic comorbidities. Cervical spine involvement, especially atlantoaxial subluxation (AAS), can lead to spinal cord compression and neurological deficits. While disease-modifying antirheumatic drugs (DMARDs) are standard therapy, intolerance to agents like methotrexate (MTX) in elderly or comorbid patients limits options. Molecular hydrogen, with antioxidant and anti-inflammatory properties, has emerged as a potential adjuvant in autoimmune diseases. This case report describes an elderly woman with long-standing, treatment-refractory RA and severe cervical spine disease who received molecular hydrogen therapy, highlighting immunological changes, clinical outcomes, and challenges in managing RA with complex comorbidities.

Case report: An 85-year-old Taiwanese woman with long-standing rheumatoid arthritis (2010 American College of Rheumatology/European League Against Rheumatism criteria) and multiple comorbidities discontinued methotrexate in 2016 due to pancytopenia. Her RA was managed with oral steroids and hydroxychloroquine, but she had recurrent hospitalizations for flares with multiple joint pain. Molecular hydrogen therapy was initiated in June 2023 as an adjuvant treatment. Fatigue, assessed using the Taiwan Brief Fatigue Inventory (BFI-T), improved notably across multiple domains, accompanied by dynamic changes in immune cell populations suggesting immunomodulatory effects. During this admission, atlantoaxial subluxation was diagnosed, fulfilling surgical criteria; however, the patient and her family declined surgery due to risk and prognosis, opting for palliative care until her death.

Conclusion: This case highlights the potential immunomodulatory benefits of molecular hydrogen as an adjuvant therapy in rheumatoid arthritis. Although clinical and immunological improvements were observed, larger studies with longer follow-up are needed. It also illustrates severe cervical spine involvement, atlantoaxial subluxation, underscoring the complexity and neurological risks of advanced RA.

Background/aim: Pediatric palliative care, particularly in oncology, is aimed at improving the quality of life for children with cancer and other life-limiting conditions. With an increase in the pediatric population eligible for such care, the need for multidisciplinary approaches and the integration of personalized care strategies emerges.

Materials and methods: We conducted a systematic review to analyze the available evidence regarding the most effective interventions, with particular attention to pharmacological assistance, home management, and the central role of the nurse in childcare. The literature search was conducted through the databases PubMed, CINAHL, Google Scholar, and Scopus, encompassing studies published between 2000 and 2024, with a focus on children aged 0 to 2 years.

Results: Ten key studies were identified that highlighted the importance of the multimodal approach in pediatric palliative care. The main interventions include the use of sedative drugs for symptom management, electronic symptom monitoring to improve family involvement, the importance of pain therapy, and the effectiveness of home care, as preferred by most families.

Conclusion: A care model that integrates multiple strategies, supported by a multidisciplinary team, is essential to ensure the optimal well-being of children in critical conditions. However, the paucity of specific studies on the 0-2 age group and the lack of standardized protocols represent significant limitations in clinical practice.

Background/aim: Tumor boards (TUBs) are interdisciplinary meetings designed to determine the most effective cancer therapies and improve patient outcomes. This study aimed to assess which TUB therapy recommendations were easily implemented and to identify factors that hindered their implementation in clinical practice.

Patients and methods: In this retrospective study, data from ten TUBs held at the University Hospital Bonn between 2014 and 2016 were analyzed. The dataset included 7,152 patients and 13,050 therapy recommendations. The degree of adherence to the recommended therapies was classified into four categories. Additionally, reasons for deviations from the recommendations were categorized based on medical record reviews.

Results: On average, 84.2% of recommendations were implemented: 68.1% were fully and 16.1% partially implemented. Deviations occurred in 8.6% of cases. The most common reasons for partial implementation were therapy changes based on new clinical findings or physician decisions (16.7%) and patient preferences (10.4%). The leading reason for complete deviation from the recommendation was lack of documentation (51.3%).

Conclusion: Most TUB recommendations across ten medical disciplines were fully or partially implemented. However, there remains potential for improvement, particularly in ensuring consistent documentation and integrating patient preferences into clinical decision-making.

Background/aim: Anamorelin, a ghrelin receptor agonist, increases body weight and lean body mass (LBM); however, its effects on the gut microbiota remain unclear. Furthermore, the predictive value of nutritional scores, such as the Controlling Nutritional Status (CONUT) score, for anamorelin response is not established. This study aimed to evaluate the effects of anamorelin on body weight, quality of life (QOL), and gut microbiota in patients with advanced cancer and cachexia, and to clarify the predictive role of nutritional indicators.

Patients and methods: This single-center prospective observational study enrolled cachectic patients (non-small cell lung, pancreatic, gastric, or colorectal cancer) receiving anamorelin 100 mg/day with dietary counseling. Outcomes included change in body weight (baseline, 3, 6, 12 weeks), QOL (EORTC QLQ-C15-PAL), and gut microbiota diversity. The association between the baseline CONUT score and weight gain (>0 kg at 6 weeks) was analyzed.

Results: Sixteen patients were analyzed. Body weight significantly increased from baseline at weeks 3, 6, and 12 (mean change at 12 weeks: +2.61±0.72 kg, p=0.008). In the eight patients assessed for QOL, the overall scale showed no significant change. The score for appetite loss (Q8) was 2.125±0.835 at 0 weeks vs. 1.375±0.744 at 6 weeks (unadjusted p=0.033). Gut microbiota alpha and beta diversity showed no significant change. A high baseline CONUT score (≥5) was associated with failure to gain weight in six weeks compared to a score <5 (87.5% of non-gainers had a high score vs. 12.5%; unadjusted p=0.01).

Conclusion: In this pilot study, anamorelin significantly increased body weight and suggested an improvement in appetite in patients with cancer and cachexia. No significant changes in overall QOL or gut microbiota diversity were detected at 6 weeks. The finding that a high baseline CONUT score may predict a lack of short-term weight gain warrants further investigation.

Background/aim: Drug metabolism and thus drug efficacy can be affected by individual differences in cytochrome P450 2D6 enzyme (CYP2D6) due to genetic polymorphism in its gene. In this study, we aimed to investigate CYP2D6 allelic variants in drug metabolism among patients with COVID-19 with comorbidities.

Patients and methods: This prospective case-control study, approved by the Pamukkale University Ethics Committee, investigated CYP2D6 polymorphisms (*4, *5, *7, *10) and COVID-19 outcomes in the Emergency Department between April and June 2020. Genomic DNA was extracted from whole blood, and genotyping was performed by polymerase chain reaction followed by sequencing on the ABI PRISM 7700 platform. Statistical analyses, including Student's t-test, Mann-Whitney U-test, chi-square test, and Fisher's exact test, were performed for laboratory and clinical data comparing between wild-type and heterozygous variants, and significance was determined as p<0.05. Data visualization was performed using SankeyMATIC, STATA 16.1 SE, and GraphPad Prism 5.0.

Results: Among the 99 patients, 71 were identified as having one or more comorbid conditions. Comorbidity analysis showed that the absence of comorbidities was most common in CYP2D6*4 (38.46%), *5 (40%), and *7 (29.63%) heterozygotes, while hypertension and diabetes were also common. CYP2D6*10 heterozygotes (n=3) presented with cardiovascular diseases, osteomalacia, and arrhythmia. In particular, CYP2D6*5 heterozygotes had significantly lower lymphocyte counts. A trend toward differences was observed for hemoglobin in CYP2D6*4 and platelet count for CYP2D6*5 and CYP2D6*10, but these were not statistically significant.

Conclusion: This study highlights the diverse clinical profiles of COVID-19 patients with different CYP2D*6 variants, particularly the association between CYP2D6*5 heterozygosity and a reduced lymphocyte count.

Background/aim: This study aimed to review the influence of different total antioxidant capacity (TAC) on the incidence of postoperative complications of cataract surgery.

Materials and methods: A prospective, non-randomized controlled trial was conducted, and individuals who received cataract surgery were enrolled. These individuals were then categorized into groups according to the mean TAC levels of the whole population, resulting in 25 eyes assigned to the high-TAC group and 30 eyes to the low-TAC group. The main outcomes were postoperative superficial keratitis, anterior chamber (AC) inflammation, corneal edema, and ocular hypertension. The generalized linear mixed model was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for the main outcomes between groups.

Results: One day postoperatively, the uncorrected distance visual acuity (UDVA) was significantly better in the high-TAC group (p=0.002), and the high-TAC group also had a higher sphere power and lower cylinder power (both p<0.05). Regarding postoperative conditions, the incidence of corneal edema (p=0.007) and ocular hypertension (p=0.028) were significantly lower in the high-TAC group. There was no preoperative parameter, which was associated with corneal edema or ocular hypertension in the high-TAC group (all p>0.05). Dense cataract and high axial length (AXL) were correlated with a higher risk of postoperative corneal edema in the low-TAC group (both p<0.05), and dense cataract was associated with higher postoperative ocular hypertension rate in the low-TAC group (p=0.033).

Conclusion: A low TAC status is associated with a higher incidence of postoperative corneal edema and ocular hypertension.

Background/aim: Zinc (Zn) deficiency is common among patients with cirrhosis and is associated with hepatic encephalopathy, immune dysfunction, and sarcopenia. In Japan, cell-free and concentrated ascites reinfusion therapy (CART) is widely employed for refractory ascites, effectively restoring albumin (ALB) and coagulation factors. However, its effect on trace elements has not been investigated. This retrospective study aimed to assess Zn concentration changes in ascitic fluid before and after CART in patients with cirrhotic refractory ascites.

Patients and methods: Data from 24 patients with decompensated cirrhosis who underwent CART at Nara Medical University Hospital between June 2022 and May 2024 were analyzed. The concentrations of Zn and ALB in original and processed ascitic fluid were measured.

Results: Among the cohort (mean age, 66.3±13.7 years, 69.6% men), 75.0% had Child-Pugh class C cirrhosis. The mean volume of drained ascitic fluid was 5,947.2±2,345.9 ml, whereas that of processed ascitic fluid was 350.6±167.6 ml. Positive correlations were observed between serum Zn and serum albumin (ALB) levels as well as ascitic Zn and ascitic ALB levels. The Zn concentration significantly increased from 12 μg/dl in the original ascitic fluid to 119 μg/dl in the processed ascitic fluid (p<0.001). The calculated recovery rates for Zn and ALB, based on the ratio of total Zn and ALB content in processed versus original fluid, were approximately 70% and 80%, respectively.

Conclusion: CART markedly increases Zn concentration in ascitic fluid, which may contribute to the restoration of micronutrient levels in patients with cirrhosis. Further studies should determine whether reinfusion of Zn-rich processed ascitic fluid increases serum Zn levels and enhances clinical outcomes.

The recurrent laryngeal nerve (RLN), a branch of the vagus nerve, plays a crucial role in phonation, respiration, and airway protection. Dysfunction of the RLN can result from various factors, including trauma, surgery, endotracheal intubation, infection, and systemic diseases, leading to clinical symptoms such as hoarseness, stridor, dysphagia, and severe respiratory distress. This systematic review examines the impact of systemic diseases on RLN function. Through an analysis of cases from the English literature, the review demonstrates that RLN dysfunction in the context of systemic diseases is multifactorial, often involving complex pathophysiology. Key findings highlight that RLN dysfunction can be caused by autoimmune, inflammatory, and neurological conditions, as well as medications. The review discusses the diagnostic challenges associated with these conditions, as symptoms often overlap with other disorders, complicating accurate diagnosis. The importance of early recognition and a multidisciplinary approach to management is emphasized, with the goal of improving patient outcomes. Ultimately, increased awareness and understanding of the diverse causes of RLN dysfunction in systemic diseases are essential for effective diagnosis and management.

Background/aim: This study aimed to assess the time advantages of delivering adjuvant hypofractionated radiotherapy (AH-RT) before third-generation adjuvant chemotherapy (A-CT), compared to the standard sequence (A-CT before AH-RT), in node-positive breast cancer (BC).

Patients and methods: A total of 45 patients with node-positive BC treated with AH-RT before third-generation A-CT at our institution between 2022 and 2023 (EXP group) were retrospectively enrolled and matched with a control group of 45 patients treated with standard sequencing (CTRL group). The primary endpoints were as follows: gain in time to RT initiation and overall treatment time, RT delay, RT interruptions, which were compared between the two groups. Propensity score matching was performed. Univariate and multivariate Cox-proportional hazards models were generated. Data from the multivariate analysis were confirmed by Pearson's covariance test, assuming p<0.001.

Results: A significant reduction in the time to AH-RT initiation and overall adjuvant treatment time was recorded in the EXP group. In the EXP group, the mean duration of the entire adjuvant treatment was 35 (29-40) weeks after surgery vs. 42 (39-50) weeks for the CTRL group (p=0.032). Hematological G2-G3 toxicity was responsible for RT delay (p=0.022) in the CTRL group. Multivariate analysis confirmed that acute skin toxicity was significantly associated with RT delay and interruption in the AH-RT15 CTRL arm (p=0.033) in the CTRL group. Pearson's covariance test confirmed these effects for the CTRL group (p<0.001).

Conclusion: Treatment with AH-RT before third-generation A-CT was found to be safe with a low acute toxicity profile in node-positive breast cancer, providing an advantage in shortening the time from surgery to AH-RT initiation as well as the overall adjuvant treatment time.

Background/aim: Cancer-induced bone pain (CIBP) due to metastatic breast cancer is common and debilitating. Effective, long-term treatment options have side-effects that reduce patients' quality of life. Preclinical models are valuable tools for testing novel analgesics, but new methods that are translationally and clinically relevant are necessary. This study aimed to assess spontaneous pain-like behavior of home cage activity and wheel running in Digital Ventilated Cages^®.

Materials and methods: Twenty BALB/cAnNHsd mice were housed in Digital Ventilated Cages^® from Tecniplast^® with GYM500 home cage running wheels. Ten mice underwent 4T1-Luc2 mammary gland adenocarcinoma cell inoculation into the right femur to establish CIBP and another ten mice underwent a sham procedure. Mice were assessed by limb use and static weight bearing to determine the development of CIBP and this was compared to the dark-phase home cage activity and wheel running in the Digital Ventilated Cages^®.

Results: The 4T1-Luc2-inoculated mice displayed pain-like behavior in limb-use and weight-bearing tests, demonstrating a preference for the contralateral limb. The limb-use scores were compared with home cage activity and wheel running. Reduced wheel running distance corresponded to reduced limb-use scores, with the shortest wheel running distances corresponding to the lowest scores. However, this behavioral pattern was not observed in home-cage activity, which remained consistent throughout the study.

Conclusion: Wheel running behavior appears to be affected by the development of metastatic breast cancer. Wheel running in a Digital Ventilated Cage^® may be a useful behavioral assessment of spontaneous pain-like behavior of CIBP and may be useful to assess analgesic efficacy.