Comparison of assistance preferences of older adults with different functional dependence levels on domestic tasks performed by robots.

BACKGROUND: Robots have the potential to assist older adults in their home-based daily living tasks. Previous studies indicated that older adults generally accept robot assistance. However, the preferences of older adults with different functional dependence levels are lacking. These older adults encounter varying levels of difficulty in daily living and may have distinct preferences for robot assistance. This study aimed to describe and compare the preferences for robot assistance on domestic tasks in older adults with different functional dependence levels. METHODS: This cross-sectional descriptive study recruited a convenience sample of 385 older adults in Hong Kong. They were categorized as independent, partially dependent, and dependent using the Katz Index of Independence in Activities of Daily Living. Their preferences for robot assistance on a list of 48 domestic tasks under six categories were assessed through the Assistance Preference Checklist. Differences in preferences between the three groups were compared using one-way ANOVA test. RESULTS: Findings revealed the differences and similarities in preferences between participants with different dependence levels. In most domestic tasks under the personal care category, dependent and partially dependent older adults reported a significantly lower preferences for human assistance or a higher preferences for robot assistance (p < 0.001), compared with the independent ones. The effect size varied from medium to large (eta squared = 0.07 to 0.52). However, participants, regardless of functional dependence levels, preferred human to assist in some domestic tasks under the health and leisure activities category and preferred robot to assist in most of the domestic tasks under the chores, information management, and manipulating objects category. CONCLUSIONS: Older adults with different levels of functional dependence exhibit different preferences for robotic assistance. To effectively use robots and assist older adults as they age, the specific preferences of older adults must be considered before designing and introducing robots in domestic care.

Quality improvement of pediatric colonoscopy by application of bundle and centralization: A single-center review.

BACKGROUND: To assess the quality change of our single-center pediatric colonoscopy after applying bundle for bowel preparation and general anesthesia and centralize the procedure using terminal ileum (TI) intubation rate as the main indicator. METHODS: All elective colonoscopies performed for patients younger than 18 years old in MacKay Memorial Hospital from July 2015 through June 2020 (assigned to group 1, before bundle) and from August 2020 through July 2021 (assigned to group 2, after bundle) were retrospectively reviewed for demographic characteristics, indications, bowel preparation agent and cleansing level, diagnostic and therapeutic procedures, maximum intestinal level reached, and cecal intubation and total procedure time. Statistical analysis was done using P value < 0.05 considered to be significant. RESULTS: Analysis included 45 and 32 colonoscopies in group 1 and 2, respectively. Bloody stool was the most frequent indication in both groups. Both TI intubation rate (42.2 % vs. 75.0 %, P = 0.004) and biopsy rate (45.0 % vs. 75.9 %, P = 0.01) increased significantly from group 1 to group 2. The narrower standard deviation of bowel preparation score (1.93 vs. 1.15) and total procedure time (37.71 vs. 22.29) in group 2 indicated a more stable quality, although the mean showed no difference. There was no statistical difference in age, gender, body weight, cecal intubation rate, or cecal intubation time. CONCLUSION: A higher TI intubation rate and biopsy rate indicated an improved quality of pediatric colonoscopy after applying bundle including bowel preparation and general anesthesia, with additional centralization.

SLCO1B1 and SLCO1B3 genetic mutations in Taiwanese patients with Rotor syndrome.

Rotor syndrome is a rare, benign, inherited disorder that is commonly associated with mild hyperbilirubinemia. It is caused by bi-allelic pathological variants in both SLCO1B1 and SLCO1B3 genes, causing defective OATP1B1 and OATP1B3 in the sinusoidal membrane and interrupted bilirubin uptake of the hepatocytes. We report five Taiwanese pediatric and adult patients aged 5-32 years presenting with conjugated hyperbilirubinemia, and were found to have genetic variants of SLCO1B1 and SLCO1B3. Two also had history of prolonged neonatal jaundice. Genetic analysis using panel-based next generation sequencing revealed three patients with homozygous mutations c.1738C>T (p.R580∗) in SLCO1B1 and a transposon LINE-1 insertion in SLCO1B3, one patient with homozygous mutations for another haplotype, c.757C>T (p.R253∗) in SLCO1B1 and c.1747+1G>A in SLCO1B3. Another patient had heterozygous c.1738C>T (p.R580∗) in SLCO1B1 linked with a LINE-1 insertion in SLCO1B3, and heterozygous c.757C>T (p.R253∗) in SLCO1B1 linked with c.1747+1G>A in SLCO1B3. In conclusion, we present the first time of genetic diagnosis of Rotor syndrome in Taiwan. Advanced genetic testing has enhanced the diagnosis of rare diseases with mild symptoms.

Localization and Laparoscopic Excision of Gastric Heterotopic Pancreas in a Child by Endoscopic SPOT® Tattooing.

Heterotopic pancreas (HP) is defined as pancreatic tissue lacking vascular or anatomic connection with the normal pancreas. Surgical resection is often indicated for symptomatic gastric HP. However, intraoperative identification of gastric HP is often difficult during laparoscopic surgery. Herein, we describe a patient with gastric HP, which was marked with SPOT® dye (GI Supply, Camp Hill, PA, USA). The dye was seen clearly laparoscopically facilitating total excision of the lesion. The final pathology report confirmed the presence of heterotopic pancreatic tissue including pancreatic acini, small pancreatic ducts tissue with islets of Langerhans in the deep gastric submucosal area. There were no postoperative complications, and the patient was symptom-free. To the best of our knowledge, this was the first case report in the literature in which endoscopic tattooing of gastric HP before laparoscopic resection was performed. This method of localization was simple and reliable in children.

Uses of Antibiotics in Ornamental Fish in Hong Kong and the Antibiotic Resistance in the Associated Zoonotic Pathogens.

The use of antibiotics in ornamental fish is not regulated, as they are not intended for human consumption. Although antibiotic resistant bacteria have been detected in ornamental fish worldwide, there have been no studies to look at the situation in Hong Kong. Therefore, the present study was conducted to investigate the use of antibiotics in ornamental fish. Ornamental fish were purchased from five local pet fish shops and the antibiotics in carriage water were quantified using liquid chromatography tandem mass spectrometry. Moreover, Aeromonas and Pseudomonas spp. present in carriage water were isolated and their minimum inhibitory concentrations against selected antibiotics were determined. Results indicated that among the twenty antibiotics screened, doxycycline (0.0155-0.0836 µg L-1), oxytetracycline (0.0102-29.0 µg L-1), tetracycline (0.0350-0.244 µg L-1), enrofloxacin (0.00107-0.247 µg L-1), and oxalinic acid (n.d.-0.514 µg L-1) were detected in all sampled shops. Additionally, MIC results revealed that some of the Aeromonas and Pseudomonas spp. isolates were highly resistant to all antibiotics selected. Our findings confirmed that multiple antibiotics are being used in ornamental fish and the associated bacteria are resistant to selected antibiotics, suggesting that this could be a significant transmission route of antibiotic resistant bacteria to household indoor environments.

Rare presentation in a rare case of pancreatic extraosseous Ewing's sarcoma: A case report.

RATIONALE: Extraosseous Ewing's sarcoma is a rare tumor which is aggressive with poor prognosis; it can occur anywhere in the body, but scantily in the pancreas. Pancreatic Ewing's sarcoma is not reported commonly, with inconsistent clinical manifestations. In this regard, early recognition of this disease is very important for the patient's sake. PATIENT CONCERNS: A 16-year-old boy presented with left lower quadrant abdominal pain for 2 months, and left flank pain with dysuria for 1 month. DIAGNOSIS: Abdominal and renal ultrasonography found a mass between the spleen and left kidney as well as left renal pelvic dilatation. Abdominal computed tomography found a heterogenous mass derived from the tail of the pancreas. Serial examinations revealed that the mass was a pancreatic Ewing's sarcoma. Furthermore, no metastasis was documented. INTERVENTIONS: The tumor was totally excised after 6 months of chemotherapy, which included 10 courses of neoadjuvant chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide. The patient completed consolidation chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide for 5 courses. Radiotherapy was applied to the tumor-involved region and tumor bed. OUTCOMES: To date, the malignancy has not recurred since the treatment was completed 4 years ago. There are no complications from the treatment for the patient. LESSONS: The pancreas is a very rare extraosseous location for Ewing's sarcoma. Pancreatic extraosseous Ewing's sarcoma should be regarded as a differential diagnosis of non-urinary originated left flank pain with dysuria in adolescents.

A rare case of pancreatic macrocystic serous cystadenoma in an adolescent: a case report and literature review.

While serous cystadenomas of the pancreas usually consist of small cysts, one rare variant has been reported to be composed of macrocysts. Herein, we present the case of the youngest patient with macrocystic serous cystadenoma (MSC) to be reported in the literature. The patient was a 17-year-old girl who presented with the major symptoms of a palpable abdominal mass accompanied by epigastric pain and vomiting for several months. A potential malignancy could not be excluded on the basis of imaging studies, which showed a large macrocystic pancreatic tumor that was 7 cm in diameter. Owing to the patient's symptoms, after diagnosing the mass as a pancreatic cystic tumor with potential malignancy and large tumor size, surgical intervention was arranged. Pathological analysis of the biopsy sample suggested MSC. By reviewing the literature, we found several unique characters of MSCs that cause them to be frequently misdiagnosed as potential malignancies. Additionally, the age of MSC occurrence was found to be lower than of general serous cystadenomas. The potential of MSC should be kept in mind by clinicians when diagnosing young people with pancreatic macrocystic lesions.

Coexisting gastrointestinal and hepatobiliary tract anomalies in omphalocele and gastroschisis: A twenty-year experience in a single tertiary medical center.

BACKGROUND: Omphalocele and gastroschisis are the two most common congenital abdominal wall defects; however, no previous study has focused on gastrointestinal and hepatobiliary tract malformations in these two conditions. This study aimed to investigate the demographic characteristics, coexisting congenital gastrointestinal and hepatobiliary tract anomalies, hospital course, and outcomes of patients with gastroschisis and omphalocele. METHODS: This is retrospective chart review of all patients admitted to one tertiary medical center in Taiwan between January 1, 2000 and June 30, 2020 with a diagnosis of gastroschisis or omphalocele. The medical records were reviewed to obtain demographic data regarding coexisting gastrointestinal and hepatobiliary tract anomalies and outcomes. RESULTS: Of the 51 patients included, 21 had gastroschisis and 30 had omphalocele. Gastroschisis was associated with a significantly younger maternal age and a higher incidence of small for gestational age. Of the 30 patients with omphalocele, twelve had associated gastrointestinal and hepatobiliary anomalies. Seven of the 21 patients with gastroschisis had gastrointestinal anomalies, and none had hepatobiliary anomalies. Among the omphalocele patients, three (10%) had documented malrotation, and one developed midgut volvulus. Among gastroschisis patients, four patients (19%) had malrotation, and two developed midgut volvulus. There were no statistically significant differences in postoperative complications or mortality rates between those with and without gastrointestinal/hepatobiliary tract anomalies. CONCLUSION: The diversity of coexisting gastrointestinal and hepatobiliary tract anomalies is higher in the omphalocele than in gastroschisis. In addition, we demonstrate that patients with gastroschisis or omphalocele have a higher rate of intestinal malrotation and midgut volvulus.

A survey among healthcare professionals from seven countries reported diverse nutritional practices of late preterm infants.

AIM: To gain insight into nutritional practices and expected growth outcomes of infants born between 34 and 36 gestational weeks defined as late preterm infants (LPT). METHODS: An anonymous online survey among paediatricians and neonatologists from Bangladesh, Indonesia, Mexico, Nigeria, Malaysia, Singapore and Taiwan was conducted from March until October 2020. The questionnaire consisted of 40 questions on the nutritional management and expected growth outcomes of LPT in and after-hospital care. RESULTS: Healthcare professionals from low to high Human Development (HDI) countries (n = 322) and very high HDI countries (n = 169) participated in the survey. Human milk was the preferred feeding, resulting in an adequate growth of LPT (weight, length and occipitofrontal circumference), according to a majority of respondents (low to high HDI, 179/265, 68% vs. very high HDI, 73/143, 51%; p = 0.002). The expected growth outcome was higher after-hospital discharge. Less than half of healthcare professionals started enteral feeding during the 1st hour of life. Lactation difficulties, limited access to human milk fortifiers and donor human milk, especially among low to high HDI countries, were reported as major hurdles. CONCLUSION: Human milk is the first feeding choice for LPT. The diverse opinions on nutritional practices and expected growth outcomes among healthcare professionals indicate the necessity to develop general nutritional guidelines for LPT.

Blue Rubber Bleb Nevus Syndrome (BRBNS): A Rare Cause of Refractory Anemia in Children.

Refractory anemia is not uncommon in pediatric patients, and anemia caused by gastrointestinal tract bleeding should always be kept in mind. Aside from infection or intestinal malrotation related bleeding, vascular malformation should also be considered. Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder consisting of multiple venous malformations. Lack of experience in pediatric BRBNS might lead to delayed diagnosis or misdiagnosis. Herein, we report a case of an eleven-year-old boy with recurrent pallor appearance and weakness diagnosed with BRBNS. After a thorough examination, he was treated with endoscopic polypectomy, and further iron supplements and folic acid. He is now under regular follow-up at our outpatient department. No complication is noted for six months. BRBNS is a rare venous malformation syndrome that mostly involves skin and the gastrointestinal tract. Multidisciplinary approach should be arranged for diagnosis and management. Up to date, no consensus for BRBNS treatment has been reached. Management usually depends on clinical symptoms and severity of damage of involved organs. The options of treatment include conservative, medical, endoscopic, and surgical management.

Tuberculosis reactivation at ileum following immune checkpoint inhibition with pembrolizumab for metastatic nasopharyngeal carcinoma: a case report.

BACKGROUND: Tuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation. CASE PRESENTATION: A 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again. CONCLUSION: To date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model.

Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression. Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated. Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group. Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.

Importance of early detection of infantile inflammatory bowel disease with defective IL-10 pathway: A case report.

RATIONALE: Infantile inflammatory bowel disease (IBD) is an extremely rare subgroup of IBD that includes patients whose age of onset is younger than 2 years old. These patients can have more surgical interventions, and a severe and refractory disease course with higher rates of conventional treatment failure. Monogenic defects play an important role in this subgroup of IBD, and identification of the underlying defect can guide the therapeutic approach. PATIENT CONCERNS: In 2007, a 4-month-old girl from a nonconsanguineous family presenting with anal fistula, chronic diarrhea, and failure to thrive. She underwent multiple surgical repairs but continued to have persistent colitis and perianal fistulas. DIAGNOSIS: Crohn's disease was confirmed by endoscopic and histologic finding. INTERVENTION: Conventional pediatric IBD therapy including multiple surgical interventions and antitumor necrosis factor alpha agents were applied. OUTCOMES: The patient did not respond to conventional pediatric IBD therapy. Interleukin-10 (IL-10) receptor mutation was discovered by whole-exome sequencing and defective IL-10 signaling was proved by functional test of IL-10 signaling pathway by the age of 12. The patient is currently awaiting hematopoietic stem cell transplantation. LESSONS: Early detection of underlying genetic causes of patients with infantile-IBD is crucial, since it may prevent patients from undergoing unnecessary surgeries and adverse effects from ineffective medical therapies. Moreover, infantile-IBD patients with complex perianal disease, intractable early onset enterocolitis and extraintestinal manifestations including oral ulcers and skin folliculitis, should undergo genetic and functional testing for IL-10 pathway defect.

Recent advance in infant nutrition: Human milk oligosaccharides.

Breast feeding and human milk are the standards for infant feeding and nutrition. Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk. To date, more than 200 structural different HMOs have been identified and some can be synthesized by the food industry. HMOs are one of the major differences between human milk and formula milk, and current evidence demonstrates their various beneficial effects toward infants' health: acting as anti-adhesive antimicrobials, immune modulators, and intestinal cell response modulators, as well as providing prebiotics effect and neurodevelopment and cognition effects. HMOs compositions vary among mothers, influenced by the stage of lactation, duration of pregnancy and maternal genetic factors. However, there are still some unknown factors affecting the compositions of HMOs and requiring further research for clarification. A combination of preclinical and clinical cohort studies may help to identify whether an individual HMO contributes to disease protection. In recent years, 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) have been approved as food ingredients by official authorities. Infant formulae supplemented with these HMOs are well-tolerated. However, more prospective clinical studies are warranted to elucidate HMOs' significance in infant nutrition. Breast milk feeding remains the best option for infants nutrition and development. Whenever breast milk is not adequate or unavailable, infant formula supplemented with HMOs might be considered as an alternative.

Immune Modulation Effects of Lactobacillus casei Variety rhamnosus on Enterocytes and Intestinal Stem Cells in a 5-FU-Induced Mucositis Mouse Model.

BACKGROUND: Intestinal mucositis remains one of the most deleterious side effects in cancer patients undergoing chemotherapy. We hypothesize that the probiotics could preserve gut ecology, ameliorate inflammation, and protect epithelia via immune modulations of enterocytes and intestinal stem cells. Our aim is to characterize these changes and the safety of probiotics via a 5-fluorouracil- (5-FU-) induced intestinal mucositis mouse model. METHODS: 5-FU-injected BALB/c mice were either orally administrated with saline or probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35). Diarrhea scores, serum proinflammatory cytokines, and T-cell subtypes were assessed. Immunostaining analyses for the proliferation of intestinal stem cells CD44 and Ki67 were processed. Samples of blood and internal organs were investigated for bacterial translocation. RESULTS: Diarrhea was attenuated after oral Lcr35 administration. Serum proinflammatory cytokines were significantly increased in the 5-FU group and were reversed by Lcr35. A tremendous rise of the CD3+/CD8+ count and a significant decrease of CD3+CD4+/CD3+CD8+ ratios were found in the 5-FU group and were both reversed by Lcr35. 5-FU significantly stimulated the expression of CD44 stem cells, and the expression was restored by Lcr35. 5-FU could increase the number of Ki67 proliferative cells. No bacterial translocation was found in this study. CONCLUSIONS: Our results showed that 5-FU caused intestinal inflammation mainly via Th1 and Th17 responses. 5-FU could stimulate stem cells and proliferation cells in a mouse model. We demonstrate chemotherapy could decrease immune competence. Probiotics were shown to modulate the immune response. This is the first study to analyze the immune modulation effects and safety of Lactobacillus strain on enterocytes and intestinal stem cells in a mouse model.

Comprehensive Exome Analysis of Immunocompetent Metastatic Head and Neck Cancer Models Reveals Patient Relevant Landscapes.

Immunocompetent metastatic head and neck cancer (HNC) models, although scarce, can help understanding cancer progression and therapy responses in vivo. Their comprehensive genome characterizations are essential for translational research. We first exome-sequenced the two most widely used spontaneous metastatic immunocompetent models, namely AT-84 and SCC VII, followed by comprehensive genomic analyses with three prior-sequenced models (MOC2, MOC2-10, and 4MOSC2), together with patient tumors for utility assessment. AT-84 and SCC VII bear high HNC tumor resemblance regarding mutational signatures-Trp53, Fanconi anemia, and MAPK and PI3K pathway defects. Collectively, the five models harbor genetic aberrations across 10 cancer hallmarks and 14 signaling pathways and machineries (metabolic, epigenetic, immune evasion), to extents similar in patients. Immune defects in HLA-A (H2-Q10, H2-Q4, H2-Q7, and H2-K1), Pdcd1, Tgfb1, Il2ra, Il12a, Cd40, and Tnfrsf14 are identified. Invasion/metastatic genome analyses first highlight potential druggable ERBB4 and KRAS mutations, for advanced/metastatic oral cavity cancer, as well as known metastasis players (Muc5ac, Trem3, Trp53, and Ttn) frequently captured by all models. Notable immunotherapy and precision druggable targets (Pdcd1, Erbb4, Fgfr1, H/Kras, Jak1, and Map2k2) and three druggable hubs (RTK family, MAPK, and DNA repair pathways) are frequently represented by these models. Immunocompetent metastatic HNC models are worth developing to address therapy- and invasion/metastasis-related questions in host immunity contexts.

Choledochal cyst as an important risk factor for pediatric gallstones in low-incidence populations: A single-center review.

BACKGROUND: Gallstones are uncommon in infants and children and Asian children are thought to have very low risk. Diagnoses have increased in recent years with the widespread use of ultrasonography (USG). This study aimed to review our experience with risk factors, complications, and treatment of pediatric gallstones in low-incidence populations. METHODS: We retrospectively reviewed patients younger than 18 years old diagnosed with gallstones using USG between November 2006 and December 2012 in a tertiary referral hospital in Taiwan. Demographic information including age and sex, follow-up period, USG findings, predisposing factors, complications, treatment approaches and outcomes were recorded. RESULTS: Ninety-eight children with gallstones diagnosed with USG were enrolled and reviewed in our study. Females comprised 55% of patients, with no specific gender tendency. No risk factor could be identified in 30.8% of patients. The most common risk factors were cephalosporin (CS) use, presence of a choledochal cyst (CC), and spherocytosis. CS use was not associated with a higher dissolution rate. The presence of type IVa CC implied a high rate of gallstone recurrence after Roux-en-Y hepaticojejunostomy. Complications were seen in 22.4% of patients, but only two needed emergency stone removal. Expectant management was performed in 61% of patients and 62.5% of them achieved spontaneous resolution; the stone dissolution rate was not lower than in the group treated with ursodeoxycholic acid (UDCA). Stone size was significantly decreased after UDCA use if resolution did not occur. CONCLUSIONS: Pediatric gallstones showed high resolution rate, and the clinical course was largely benign. CS use was the most common risk factor and did not predict a higher dissolution rate. Type IVa CC was also an important risk factor associated with a high recurrence rate. Conservative treatment and oral UDCA may be reasonable strategies in most patients, unless complications are present.

NEWS and qSIRS superior to qSOFA in the prediction of 30-day mortality in emergency department patients in Hong Kong.

BACKGROUND: We aim to compare the prognostic value of Quick Sepsis-Related Organ Failure Assessment (qSOFA) and the previous Systemic Inflammatory Response Syndrome (SIRS) criteria, the National Early Warning Score (NEWS) and along with their combinations in the emergency department (ED). METHODS: This single-centre prospective study recruited a convenience sample of unselected ED patients triaged as category 2 (Emergency) and 3 (Urgent). Receiver Operating Characteristic analyses were performed to determine the Area Under the Curve (AUC), along with sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios for the various scores. RESULTS: Of 1253 patients recruited, overall 30-day mortality was 5.7%. The prognostic value for prediction of 30-day mortality, with AUCs for qSOFA ≥2, SIRS ≥2, NEWS ≥5, qSIRS (qSOFA + SIRS) ≥2 and NSIRS (NEWS + SIRS) ≥5 of 0.56 (95%CI 0.53-0.58), 0.61 (95%CI 0.58-0.64), 0.61 (95%CI 0.58-0.64), 0.64 (95%CI 0.62-0.67) and 0.61 (95%CI 0.58-0.63), respectively. Using pairwise comparisons of ROC curves, NEWS ≥5 and qSIRS ≥2 were better than qSOFA ≥2 at predicting 30-day mortality. CONCLUSIONS: Among unselected emergency and urgent ED patients, the prognostic value for NEWS and qSIRS were greater than qSOFA, Combinations of qSOFA and SIRS could improve the predictive value for 30-day mortality for ED patients. Key messages NEWS ≥5 and qSIRS ≥2 were better than qSOFA ≥2 at predicting 30-day mortality in ED patients. Combinations of qSOFA and SIRS could improve the predictive value for 30-day mortality for ED patients.

Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated MAPK1 mutations. Residues D321, R135, and E322 are in 3D proximity. MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K's effect is moderate.

MAPK pathway mutations in head and neck cancer affect immune microenvironments and ErbB3 signaling.

MAPK pathway mutations affect one-fifth of head and neck squamous cell carcinoma (HNSCC). Unexpectedly, MAPK pathway aberrations are associated with remarkably long patient survival, even among patients with TP53 mutations (median ∼14 yr). We explored underlying outcome-favoring mechanisms with omics followed by preclinical models. Strikingly, multiple hotspot and non-hotspot MAPK mutations (A/BRAF, HRAS, MAPK1, and MAP2K1/2) all abrogated ErbB3 activation, a well-established HNSCC progression signal. Inhibitor studies functionally defined ERK activity negatively regulating phospho-ErbB3 in MAPK-mutants. Furthermore, pan-pathway immunoprofiling investigations identified MAPK-mutant tumors as the only "CD8+ T-cell-inflamed" tumors inherently bearing high-immunoreactive, constitutive cytolytic tumor microenvironments. Immunocompetent MAPK-mutant HNSCC models displayed active cell death and massive CD8+ T-cell recruitment in situ. Consistent with CD8+ T-inflamed phenotypes, MAPK-mutant HNSCC patients, independent of tumor-mutational burden, survived 3.3-4 times longer than WT patients with anti-PD1/PD-L1 immunotherapies. Similar prognosticity was noted in pan-cancers. We uncovered clinical, signaling, and immunological uniqueness of MAPK-mutant HNSCC with potential biomarker utilities predicting favorable patient survival.