Solitary Giant Primary Gastric Plasmacytoma Mimicking Gastric Adenocarcinoma In Situ.

A solitary extraosseous plasmacytoma is a rare type of plasma cell neoplasm. Its occurrence in the stomach is particularly unusual and can easily be mistaken for more common types of tumors. We describe a case involving a solitary extraosseous plasmacytoma in a patient who experienced weight loss as the sole symptom. Initially, the condition was misdiagnosed as gastric adenocarcinoma based on endoscopic biopsy results, leading to a gastrectomy after neoadjuvant chemotherapy. Subsequent examination of the pathological specimen revealed the presence of plasma cell neoplasia alongside a gastric adenocarcinoma in situ.

Mother-Offspring Bonding after Calving in Water Buffalo and Other Ruminants: Sensory Pathways and Neuroendocrine Aspects.

The cow-calf bonding is a process that must be developed within the first six hours after calving. Both the buffalo dam and the newborn calf receive a series of sensory cues during calving, including olfactory, tactile, auditory, and visual stimuli. These inputs are processed in the brain to develop an exclusive bond where the dam provides selective care to the filial newborn. The limbic system, sensory cortices, and maternal-related hormones such as oxytocin mediate this process. Due to the complex integration of the maternal response towards the newborn, this paper aims to review the development of the cow-calf bonding process in water buffalo (Bubalus bubalis) via the olfactory, tactile, auditory, and visual stimuli. It will also discuss the neuroendocrine factors motivating buffalo cows to care for the calf using examples in other ruminant species where dam-newborn bonding has been extensively studied.

Human animal relationships in Bos indicus cattle breeds addressed from a Five Domains welfare framework.

The present review has two objectives, the first is to investigate the differences in temperament between Bos indicus and Bos taurus breeds and determining the effects on production due to positive treatment and to compare this with negative HAR, by using the Five Domain Model as framework. The second objective is to discuss potential strategies to achieve better HAR when working with Bos indicus cattle. Bos indicus are more reactive and temperamental than Bos taurus cattle. When human animal relationships (HAR) are evaluated, Bos indicus cattle may react with greater intensity. They may be more likely to develop a negative emotional state, especially in extensively raised Bos indicus cattle that are handled only a few times each year. Bos indicus cattle can have positive emotional states when they have frequent positive interactions with people. Interactions with people, both positive and negative, would be in the fourth Domain of the Five Domains model. Cattle that are more reactive during handling may also have lower weight gain, even when they have abundant feed. This would be in the first Domain of Nutrition. When cattle are handled in races and corrals, injuries may be more likely to occur. Injuries and bruises would be in the third Domain of Health. Injuries could be caused by either poor handling practices by people or poor handling facilities. Yelling or electric prod use would be examples of poor HAR. Second Environmental Domain issues may be broken facilities or slick, slippery floors that are associated with falls.

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes.

BACKGROUND: Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus (T2DM), that is, patients who have insulin resistance, obesity, and other cardiovascular risk factors, suggesting that the presence of glutamic acid decarboxylase (anti-GAD65), islet antigen 2 (anti-IA2), and zinc transporter 8 (anti-Zn8T) antibodies could have deleterious effects on beta cell function, causing failure and earlier requirement for insulin treatment. AIM: To evaluate anti-GAD65, anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM. METHODS: This was a case-control study in patients with clinically diagnosed with T2DM (68 cases and 64 controls with and without early insulin dependence respectively), male and female, aged 12-18 years. Somatometry, blood pressure, glucose, insulin, C-peptide, glycated hemoglobin A1c, and lipid profiles were assessed. ELISA was used to measure anti-GAD65, anti-IA2, and anti-Zn8T antibodies. Descriptive statistics, Pearson's χ 2 test, Student's t test, and logistic regression was performed. P < 0.05 was considered statistically significant. RESULTS: There were 132 patients (53.8% female), with a mean age was 15.9 ± 1.3 years, and there was a disease evolution time of 4.49 ± 0.88 years. The presence of anti-GAD65, anti-IA2, and anti-Zn8T positivity was found in 29.5%, 18.2%, and 15.9%, respectively. Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity: anti-GAD65 odds ratio (OR): 2.42 (1.112-5.303, P = 0.026); anti-IA2: OR: 1.55 (0.859-2.818, P = 0.105); and anti-Zn8T: OR: 7.32 (2.039-26.279, P = 0.002). CONCLUSION: Anti-GAD65 positivity was high in our study. Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype, leading to an increased risk of early insulin dependence.

Nutritional Management of Patients with Fatty Acid Oxidation Disorders.

Treatment of fatty acid oxidation disorders is based on dietary, pharmacological and metabolic decompensation measures. It is essential to provide the patient with sufficient glucose to prevent lipolysis and to avoid the use of fatty acids as fuel as far as possible. Dietary management consists of preventing periods of fasting and restricting fat intake by increasing carbohydrate intake, while maintaining an adequate and uninterrupted caloric intake. In long-chain deficits, long-chain triglyceride restriction should be 10% of total energy, with linoleic acid and linolenic acid intake of 3-4% and 0.5-1% (5/1-10/1 ratio), with medium-chain triglyceride supplementation at 10-25% of total energy (total MCT+LCT ratio = 20-35%). Trihepatnoin is a new therapeutic option with a good safety and efficacy profile. Patients at risk of rhabdomyolysis should ingest MCT or carbohydrates or a combination of both 20 min before exercise. In medium- and short-chain deficits, dietary modifications are not advised (except during exacerbations), with MCT contraindicated and slow sugars recommended 20 min before any significant physical exertion. Parents should be alerted to the need to increase the amount and frequency of carbohydrate intake in stressful situations. The main measure in emergency hospital treatment is the administration of IV glucose. The use of carnitine remains controversial and new therapeutic options are under investigation.

Advances in Light-Responsive Smart Multifunctional Nanofibers: Implications for Targeted Drug Delivery and Cancer Therapy.

Over the last decade, scientists have shifted their focus to the development of smart carriers for the delivery of chemotherapeutics in order to overcome the problems associated with traditional chemotherapy, such as poor aqueous solubility and bioavailability, low selectivity and targeting specificity, off-target drug side effects, and damage to surrounding healthy tissues. Nanofiber-based drug delivery systems have recently emerged as a promising drug delivery system in cancer therapy owing to their unique structural and functional properties, including tunable interconnected porosity, a high surface-to-volume ratio associated with high entrapment efficiency and drug loading capacity, and high mass transport properties, which allow for controlled and targeted drug delivery. In addition, they are biocompatible, biodegradable, and capable of surface functionalization, allowing for target-specific delivery and drug release. One of the most common fiber production methods is electrospinning, even though the relatively two-dimensional (2D) tightly packed fiber structures and low production rates have limited its performance. Forcespinning is an alternative spinning technology that generates high-throughput, continuous polymeric nanofibers with 3D structures. Unlike electrospinning, forcespinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This review addresses current trends and potential applications of light-responsive and dual-stimuli-responsive electro- and forcespun smart nanofibers in cancer therapy, with a particular emphasis on functionalizing nanofiber surfaces and developing nano-in-nanofiber emerging delivery systems for dual-controlled drug release and high-precision tumor targeting. In addition, the progress and prospective diagnostic and therapeutic applications of light-responsive and dual-stimuli-responsive smart nanofibers are discussed in the context of combination cancer therapy.

Assessment of the nociceptive response to the use of cannabidiol alone and in combination with meloxicam through infrared pupillometry in female dogs undergoing elective ovariohysterectomy.

The negative effects of pain are a constant concern in the surgical management of animals, leading to the search for new drugs or more effective analgesic protocols to control this negative emotion. This study aimed to evaluate the nociceptive response of cannabidiol (CBD) alone and in combination with meloxicam using infrared pupillometry in female dogs undergoing elective ovariohysterectomy (OVH) under isoflurane anesthesia. A total of 60 female dogs of different breeds were included. These dogs were randomly assigned to four study groups according to the treatment: Control Group (G0: n = 15) receiving saline solution; group premedicated with meloxicam at a dose of 0.2 mg Kg-1 IV (GMelox: n = 15). Postoperatively this drug was used at 0.1 mg Kg-1 IV every 24 h; the CBD-treated Group (GCBD: n = 15) at a dose of 2 mg Kg-1 orally in the preoperative. Postoperatively was administrated every 12 h; and the Group premedicated with the combination of meloxicam and CBD (GMelox/CBD: n = 15) Meloxicam at a dose of 0.2 mg Kg-1 IV preoperatively, and 0.1 mg Kg-1 IV during the postoperative. CBD at a dose of 2 mg Kg-1 orally in the preoperative, and every 12 h in the postoperative. Treatments were administered for 48 postoperative hours. After OVH, the pupillary neurologic index, pupillary size, minimum diameter (MIN), percentage change, constriction latency (Lat), constriction velocity, and maximum constriction velocity were recorded as pupillometric variables in both eyes during events (E): Baseline (30 min before drug administration), E30 min, E1h, E2h, E3h, E4h, E8h, E12h, E24h, and E48h. The Short-Form of the Glasgow Composite Measure Pain Scale (GCMPS-SF) was used to assess pain during the same events. Overall, it was observed that the pupillometric variables Size, MIN., and Lat. were significantly higher in G0 compared to the other groups during E30 min, E1h, and E2h (p = 0.03), indicating greater pupil dilation in G0 animals. Additionally, no statistically significant differences were observed in GCMPS-SF between GMelox, GCBD, and GMelox/CBD during the postoperative period (p > 0.05). In contrast, the scores were statistically different compared to G0 (p = 0.00001), where all animals in this group received rescue analgesia at 2 h post-surgery. According to pupillometry and scores on the GCMPS-SF scale, it was observed that monotherapy with cannabidiol provides a similar analgesic effect to meloxicam alone or in combination with cannabidiol to manage acute pain in dogs. Similarly, these findings suggest that infrared pupillometry could be a tool for recognizing acute pain in dogs.

Tactile, Auditory, and Visual Stimulation as Sensory Enrichment for Dairy Cattle.

Several types of enrichment can be used to improve animal welfare. This review summarizes the literature on the use of mechanical brushes, tactile udder stimulation, music, and visual stimuli as enrichment methods for dairy cows. Mechanical brushes and tactile stimulation of the udder have been shown to have a positive effect on milk yield and overall behavioral repertoire, enhancing natural behavior. Classical music reduces stress levels and has similarly been associated with increased milk yield. A slow or moderate tempo (70 to 100 bpm) at frequencies below 70 dB is recommended to have this positive effect. Evidence on the impacts of other types of enrichment, such as visual stimulation through mirrors, pictures, and color lights, or the use of olfactory stimuli, is equivocal and requires further study.

Application of Infrared Thermography in the Rehabilitation of Patients in Veterinary Medicine.

Infrared Thermography (IRT) has become an assistance tool in medicine and is used to noninvasively evaluate heat elimination during and after inflammatory processes or during the recovery period. However, its application in veterinary patients undergoing physiotherapy is a field that requires deep research. This review aims to analyze the application of IRT in the monitoring of animal physiotherapy, using the thermal changes that are present in patients undergoing gait or lameness issues (e.g., inflammation, pain, increased local temperature) as a neurobiological basis. Rehabilitation techniques such as acupuncture, physical therapies, thermotherapy, photo-biomodulation, and electrostimulation have been reported to have an anti-inflammatory effect that decreases the amount of local heat production, which is heat that can be recorded with IRT. Therefore, IRT could be used as a complementary tool to evaluate the effectiveness of the therapy, and it is suggested that further studies evaluate the accuracy, sensibility, and sensitivity of IRT.

Light-Responsive and Dual-Targeting Liposomes: From Mechanisms to Targeting Strategies.

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

Generalized pustular psoriasis: A nationwide population-based study using the National Health Data System in France.

BACKGROUND: GPP is a rare, chronic, neutrophilic skin disease, with limited real-world data characterizing patients with flares and the impact of flares on disease progression and morbidity. OBJECTIVE: Describe the clinical characteristics of patients with GPP, comorbidities, disease epidemiology and frequency and severity of flares, and compare patients with GPP with a matched severe psoriasis population. METHODS: In this population-based real-world cohort study an algorithm was developed to identify patients with GPP flares. Three cohorts were identified using the Système National des Données de Santé (SNDS) database covering almost the entire French population; a prevalent cohort (2010-2018), an incident cohort (2012-2015). A severe psoriasis cohort was compared with the GPP incident cohort using propensity score matching. RESULTS: The prevalent and incident cohorts comprised 4195 and 1842 patients, respectively. In both cohorts, mean age was 58 years; 53% were male. Comorbidities were significantly more common in the incident cohort versus matched psoriasis cohort, respectively, including hypertension (44% vs. 26%), ischaemic heart disease (26% vs. 18%) and hyperlipidaemia (25% vs. 15%). In the incident cohort, the flare rate was 0.1 flares/person-year and 0.4 flares/person-year among the 569 out of 1842 patients hospitalized with flares. These patients had a mean (±SD) stay of 11.6 ± 10.4 days; 25% were admitted to the intensive care unit. In 2017, the cumulative incidence and cumulative GPP age-sex standardized prevalence were 7.1 and 45.2 per million, respectively. CONCLUSIONS: Patients with GPP had a distinct comorbidity profile compared to patients with severe psoriasis, and GPP flares were associated with long hospitalizations.

Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project.

BACKGROUND: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. AIMS: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. METHODS: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant. MAIN RESULTS: Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy. CONCLUSION: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.

Uterine dynamics, blood profiles, and electronic fetal monitoring of primiparous and multiparous bitches classified according to their weight.

Perinatal mortality occurs in all species. In dogs, mortality rates have been reported to range from 5 to 35%. Electronic fetal and uterine monitoring has recently been used in domestic animals to monitor the mother and newborn before and during parturition. In this way, the fetal heart rate and uterine dynamics can be monitored. This study evaluated the uterine dynamics of bitches with different weights and parity. Ninety-six bitches and their 476 puppies were divided into four experimental groups containing 24 individuals each (12 primiparous bitches and 12 multiparous bitches), according to body weight: G1 (4-8 kg), G2 (8.1-16 kg), G3 (16.1 to 32 kg), and G4 (32.1 to 39.6 kg). The fetal heart rate decelerations (dip 2 patterns), uterine dynamics, and bitches' blood profiles were evaluated, including levels of glucose, lactate, pCO2, pO2, pH, HCO3-, and Ca++. The dam weight can affect the vitality of newborns and the uterine dynamics, with differences in the frequency, intensity, and duration of myometrial contractions. The expulsion interval between puppies was longest in primiparous bitches with low weight and shortest in multiparous bitches with high weight. The expulsion interval and the number of stillborn females were higher in primiparous bitches with high weight. Newborn male puppies were significantly heavier than newborn females.

Caffeine Administration in Piglets with Low Birthweight and Low Vitality Scores, and Its Effect on Physiological Blood Profile, Acid-Base Balance, Gas Exchange, and Infrared Thermal Response.

Intrapartum asphyxia, fetal hypoxia, and their consequences (e.g., acidosis, hypercapnia, hypoglycemia, and hypothermia) are the main factors related to physio-metabolic imbalances that increase neonatal mortality in piglets, particularly in piglets with low birthweight and low vitality scores. This study aimed to evaluate the effect of three different doses of caffeine (10, 20, and 30 mg/kg) administered orally to 480 newborn piglets with low birthweight and low vitality scores. Blood gas parameters (pH, pO2, pCO2, and HCO3-), physio-metabolic profile (Ca++, glucose, and lactate), and the thermal response assessed through infrared thermography in four thermal windows (ocular, auricular, snout, and hindlimb) and rectal temperature were evaluated during the first 24 h of life. Doses of 30 mg/kg resulted in significant differences at 24 h for all evaluated parameters, suggesting that caffeine administration improved the cardiorespiratory function and metabolic activity of piglets by reducing acidosis, restoring glycemia, and increasing surface and rectal temperature. In conclusion, caffeine at 30 mg/kg could be suggested as an appropriate dose to use in piglets with low birthweight and low vitality scores. Future research might need to study the presentation of adverse effects due to higher caffeine concentrations.

Clinical Outcomes of Patients with Chronic Neuropathic Form of Gaucher Disease in the Spanish Real-World Setting: A Retrospective Study.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1-25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.

The Challenge of Global Warming in Water Buffalo Farming: Physiological and Behavioral Aspects and Strategies to Face Heat Stress.

Water buffaloes have morphological and behavioral characteristics for efficient thermoregulation. However, their health, welfare, and productive performance can be affected by GW. The objective of this review was to analyze the adverse effects of GW on the productive behavior and health of water buffaloes. The physiological, morphological, and behavioral characteristics of the species were discussed to understand the impact of climate change and extreme meteorological events on buffaloes' thermoregulation. In addition, management strategies in buffalo farms, as well as the use of infrared thermography as a method to recognize heat stress in water buffaloes, were addressed. We concluded that heat stress causes a change in energy mobilization to restore animal homeostasis. Preventing hyperthermia limits the physiological, endocrine, and behavioral changes so that they return to thermoneutrality. The use of fans, sprinklers, foggers, and natural sources of water are appropriate additions to current buffalo facilities, and infrared thermography could be used to monitor the thermal states of water buffaloes.

Rat Grimace Scale as a Method to Evaluate Animal Welfare, Nociception, and Quality of the Euthanasia Method of Wistar Rats.

Refinement of experimental procedures in animal research has the objective of preventing and minimizing pain/distress in animals, including the euthanasia period. This study aimed to evaluate pain associated with six methods of euthanasia in Wistar rats (injectable, inhalational, and physical), by applying the Rat Grimace Scale (RGS), comparing the scores, and determining the method with the highest score that might indicate pain for laboratory rodents. Sixty adult male and female Wistar rats were used and assigned to six treatments: pentobarbital, CO2, decapitation, isoflurane, ketamine + xylazine, and ketamine + CO2. Video recording to assess the RGS scores was performed in four events: basal: 24 h before the procedure; Ti1: three minutes before the procedure; Ti2: during the application of the euthanasia method; and Ti3: immediately after the application until LORR. The main findings of this study showed that, during Ti2, decapitation and ketamine + xylazine had the highest scores (0.6 ± 0.26 and 0.6 ± 0.16, respectively) (p < 0.0001), while at Ti3, CO2 (0.9 ± 0.18) and isoflurane (1.2 ± 0.20) recorded the highest scores (p < 0.0001). According to the present results, decapitation and ketamine + xylazine elicited short-term acute pain, possibly due to tissue damage caused by both methods (injection and guillotine). In contrast, isoflurane's RGS scores recorded during Ti3 might be associated with nociception/pain due to the pungency of the drug or to the pharmacological muscle relaxant effect of isoflurane. Further research is needed to establish a comprehensive study of pain during euthanasia, where RGS could be used minding the limitations that anesthetics might have on facial expression.

Breastfeeding and Inborn Errors of Amino Acid and Protein Metabolism: A Spreadsheet to Calculate Optimal Intake of Human Milk and Disease-Specific Formulas.

Human milk (HM) offers important nutritional benefits. However, except for phenylketonuria (PKU), there are little data on optimal levels of consumption of HM and a special formula free of disease-related amino acids (SF-AA) in infants with inborn errors of metabolism of amino acids and proteins (IEM-AA-P). We designed a spreadsheet to calculate the amounts of SF-AA and HM required to cover amino acid, protein, and energy needs in patients with the nine main IEM-AA-P in infants aged under 6 months. Upon entering the infant's weight and the essential amino acid or intact protein requirements for the specific IEM, the spreadsheet calculates the corresponding required volume of HM based on the amino acid concentration in HM. Next, the theoretical daily fluid intake (typical range, 120-200 mL/kg/day) is entered, and the estimated daily fluid intake is calculated. The required daily volume of SF-AA is calculated as the difference between the total fluid intake value and the calculated volume of HM. The spreadsheet allows for the introduction of a range of requirements based on the patient's metabolic status, and includes the option to calculate the required volume of expressed HM, which may be necessary in certain conditions such as MMA/PA and UCD. In cases in which breastfeeding on demand is feasible, the spreadsheet determines the daily amount of SF-AA divided over 6-8 feeds, assuming that SF-AA is administered first, followed by HM as needed. Intake data calculated by the spreadsheet should be evaluated in conjunction with data from clinical and nutritional analyses, which provide a comprehensive understanding of the patient's nutritional status and help guide individualized dietary management for the specific IEM.

Advanced or metastatic biliary tract cancer in Japan: a study using the Japan Medical Data Center payer claims database.

Aim: Biliary tract cancers are aggressive, with poor prognosis. This study describes clinical characteristics, treatment patterns and healthcare resource utilization in patients with metastatic biliary tract cancer in Japan. Materials & methods: This cohort-based study collected data from the Japan Medical Data Center claims database (2014-2018). Results: A total of 325 patients were included; 65.2% were male and the mean age was 59.2 years. A 47.6% had an Elixhauser Comorbidity Index score ≥5. Most frequent regimens were gemcitabine + cisplatin (52.9%) for first-line therapy and tegafur + gimeracil + oteracil for second-line therapy (48.6%) and third-line therapy (27.2%). Approximately 77% of patients had ≥1 hospital admission, with a median length of 57 days. Conclusion: This study provides insights on the characteristics and burden of metastatic biliary tract cancer in Japan, highlighting high disease burden in a younger population.