Triggers of intensive care patients with palliative care needs from nurses' perspective: a mixed methods study.

PURPOSE: Triggers have been developed internationally to identify intensive care patients with palliative care needs. Due to their work, nurses are close to the patient and their perspective should therefore be included. In this study, potential triggers were first identified and then a questionnaire was developed to analyse their acceptance among German intensive care nurses. METHODS: For the qualitative part of this mixed methods study, focus groups were conducted with intensive care nurses from different disciplines (surgery, neurosurgery, internal medicine), which were selected by convenience. Data were analysed using the "content-structuring content analysis" according to Kuckartz. For the quantitative study part, the thus identified triggers formed the basis for questionnaire items. The questionnaire was tested for comprehensibility in cognitive pretests and for feasibility in a pilot survey. RESULTS: In the qualitative part six focus groups were conducted at four university hospitals. From the data four main categories (prognosis, interprofessional cooperation, relatives, patients) with three to 15 subcategories each could be identified. The nurses described situations requiring palliative care consults that related to the severity of the disease, the therapeutic course, communication within the team and between team and patient/relatives, and typical characteristics of patients and relatives. In addition, a professional conflict between nurses and physicians emerged. The questionnaire, which was developed after six cognitive interviews, consists of 32 items plus one open question. The pilot had a response rate of 76.7% (23/30), whereby 30 triggers were accepted with an agreement of ≥ 50%. CONCLUSION: Intensive care nurses see various triggers, with interprofessional collaboration and the patient's prognosis playing a major role. The questionnaire can be used for further surveys, e.g. interprofessional triggers could be developed.

Neonatal Paratesticular Abscess as the Greatest Mimicker of Testicular Torsion.

INTRODUCTION: The management of acute scrotal swelling can be challenging in neonatal age, with scrotal abscess being great mimickers of testicular torsion. CASE PRESENTATION: We report a 12-day-old previously healthy male infant who presented with 72 h of increasing right-sided scrotal swelling, without fever or irritable behavior. The left testicle was palpable, but the right side was too swollen to palpate a testicle, with absent cremasteric reflex. Biochemical analysis was normal and Doppler sonography demonstrated a hypoechogenic avascular lesion compressing the right testis, without intratesticular flow. Due to these findings, surgical exploration was undertaken on suspicion of potential testicular torsion. Purulent material was encountered and cultured. The testis and epididymis were covered by thick necrotic fibrinous exudate, with no spermatic cord torsion. Gentamicin and vancomycin were begun immediately. The patient remained afebrile and the scrotal induration gradually subsided. Urine and blood cultures were sterile. On the second postoperative day, cultures yielded Escherichia coli sensitive to gentamicin. One-month follow-up testicular ultrasound demonstrated complete inflammation resolution. CONCLUSION: Paratesticular abscess may be considered as the greatest mimicker of testicular neonatal torsion, due to the frequent absence of classical signs of inflammation. Early surgical exploration can be diagnostic and therapeutic and should be performed in these cases.

Cooling Holstein cows for 60 days prepartum in summer: effects on prepartum physiology, postpartum productivity, and calf growth.

Heat stress (HS) during the dry period of dairy cows in hot and dry conditions compromises the physiological status and mammary gland development of dairy cows, thereby negatively affecting milk component yield in the subsequent lactation. Our objective was to evaluate the effects of cooling Holstein cows under moderate or higher HS conditions (i.e., ambient temperature higher than 30 °C, with a temperature-humidity index of 78.2 units) during the dry period on prepartum physiological status, postpartum productivity, and calf growth. Twenty-four multiparous Holstein cows were divided into two groups: one with a cooling system based on spray and fans under a pen shade (CL, n = 12) and the other not-cooled (NC, n = 12). The cooling system operated 10 h/d (09:00-19:00 h) for 60 d prepartum. During the morning, rectal temperature and respiration frequency were lower in CL cows, but not in the afternoon, which was attributed to higher (P < 0.01) dry matter intake by CL cows. Total serum protein was higher (P < 0.01) in CL cows, but hemoglobin was higher in NC cows (P < 0.01), with no differences in other electrolytes, hormones, hematological components, and metabolites. Milk fat and fat and fat-protein corrected milk were higher (P < 0.05) in CL cows. Female and birth weight trended (P = 0.08) to be higher in CL cows. Cooling cows during the dry period had a limited effect on physiology prepartum but increased postpartum productivity of Holstein cows under hot and dry conditions.

Region of Murcia's 2022 report card on physical activity for children and youth.

Objective: The aim of this review was to summarize the process and results of the Region of Murcia's 2022 Report Card on Physical Activity for Children and Youth. Methods: Indicators from the Global Matrix initiative (Overall Physical Activity, Organized Sport & Physical Activity, Physical Fitness, Active Play, Active Transport, Sedentary Behaviors, Family & Peers, School, Community & Environment, and Government) were evaluated based on the best available data in the Region of Murcia. Results: Active play was the indicator with the highest grade (B+), followed by Organized Sport & Physical Activity (B) and Active Play (B). School and Family and Peers indicators obtained a C+ and C grade, respectively. Both Community and Environment and Sedentary Behaviors indicators received a D+ grade. The grade for Overall Physical Activity and Government indicators was D. Physical Fitness was the indicator with the lowest grade of this Report Card (D-). None of the indicators received an incomplete grade (INC) because of a lack of available information. Conclusions: The present Report Card offers evidence highlighting the low level of physical activity in Spanish children and adolescents living in the Region of Murcia. Further studies and surveillance efforts are urgently needed for most of the indicators analyzed, which should be addressed by researchers and the Region of Murcia's Government for this specific population. A strong commitment from the Government of the Region of Murcia is needed at all levels to promote a cultural change that will lead children and young people in this region to improve the current situation.

Mortality predictive factors in congenital hepatic hemangioma: a case-control study.

Congenital hepatic hemangiomas (CHHs) are benign vascular tumors whose clinical, histological, and genetic correlation has recently been described in patients with long-term survival, although no mortality risk factors have been identified to date. The aim of this study is to analyze predictors of mortality in patients with CHH. A retrospective single-center case-control study of consecutive CHH patients diagnosed in our institution between 1991 and 2021 was performed, who were classified into two groups according to their survival. Demographic, gestational, imaging, and laboratory data at diagnosis were collected and compared between both groups. A total of 29 patients were included (12 males; 17 females) of whom 5 died as a result of CHH evolution due to cardiac failure and coagulopathy, with a median age of 11 days until death. No differences in demographic or gestational data were reported. There were neither differences when comparing imaging tests, nor in location, number of affected liver segments, or CHH estimated volume. Upon laboratory data at diagnosis, deceased patients had a significant elevation of median liver enzymes [glutamic-oxaloacetic transaminase (359 u/L vs. 45 u/L; p < 0.01) and glutamic-pyruvic transaminase (313 u/L vs. 20 u/L; p < 0. 01)], as well as a decreased median platelet count (85,250/µL vs. 337,000/µL; p < 0.01), prothrombin activity (54% vs. 93%; p < 0.01), and fibrinogen (131 mg/dL vs. 284 mg/dL; p < 0.01), with no differences in blood count or biochemistry data. CONCLUSIONS: CHH clinical behavior can be innocuous or life-threatening. Thrombocytopenia, coagulation disorders, and increased liver enzymes at diagnosis seem to be the main predictors of mortality. WHAT IS KNOWN: • Congenital Hepatic Hemangiomas (CHHs) are benign vascular tumors whose clinical behavior can be innocuous or life-threatening. WHAT IS NEW: • Thrombocytopenia, coagulation disorders and increased liver enzymes at diagnosis seem to be the main predictors of mortality in these patients.

The effectiveness of matrix ablation with silver nitrate in the treatment of ingrown toenails. A single-center case-control study.

BACKGROUND: Partial onychectomy with chemical matrixectomy is considered the gold standard treatment for stage II-III ingrown toenails (IT). However, there are scarce reports describing the use of silver nitrate in IT management in adolescents. Our aim is to analyze the effectiveness of matrix ablation with silver nitrate and compare it with partial onychectomy by electrocautery. METHODS: A retrospective study of adolescent patients with stage II-III IT was performed. Those who underwent electrocautery matricectomy in a major outpatient surgical center (Group A) and those who were treated with silver nitrate at an outpatient clinic (Group B) were compared. Efficacy was determined by recurrence and postoperative infection rates. RESULTS: Two hundred and nine patients were included (86 group A; 123 group B), with a total of 382 partial onychectomies (151 group A; 231 group B). Group B patients exhibited a lower recurrence rate (4.7%) when compared to group A (11.2%, p = .02), and had a lower postoperative infection rate (4.0% group A vs. 1.7% group B; p = .18), although not statistically significant. CONCLUSION: Silver nitrate chemical matricectomy after partial onychectomy is an effective treatment for IT in adolescents, with few postoperative complications and low recurrence rate. Therefore, it should be considered as a possible alternative to electrocautery matricectomy.

How does the number of training years in pediatric surgery affect appendectomy outcomes?

INTRODUCTION: Appendectomy has traditionally been considered as a training operation for junior pediatric surgeons during their training period. However, with the increase of laparoscopic appendectomy, there has been a growing concern about the performance of this procedure by junior trainees. Our aim is to analyze intra-/postoperative appendectomy outcomes according to the number of training years during Pediatric Surgical residency training program. METHODS: A retrospective study was performed in patients who underwent appendectomy between 2018 and 2021 in our institution, who were divided into 5 groups according to the number of training years of the junior surgeon who performed the intervention (Y1-Y5). Demographics, complicated appendicitis rate, operation time, and postoperative complications were compared. A stratified analysis according to the technique performed (open/laparoscopic) was performed. RESULTS: A total of 1274 appendectomized patients were analyzed, of which 1257 (98.7%) were operated on by junior trainees (81 in Y1; 407 in Y2; 337 in Y3; 261 in Y4; and 171 in Y5) without demographic differences between groups. As the year of training increased, an elevation in complicated appendicitis rate was observed, although without statistically significant differences. However, laparoscopic/open appendectomies ratio increased with increasing year of training (p < 0.001). Operative time decreased significantly with increasing year of training (p < 0.001), both in open and laparoscopic appendectomies. There were no significant differences in postoperative complications, nor in the stratified analysis according to surgical technique. CONCLUSION: Appendectomy performed by junior pediatric surgery trainees can be considered a safe procedure from the first year of training, regardless of the technique used.

Does the timing of appendectomy affect outcomes and postoperative complications?

PURPOSE: There is controversy about the necessity of nighttime appendectomy. The aim of this study was to determine whether timing of appendectomy performance plays a role on postoperative complications. METHODS: A retrospective single-center comparative study was performed in children who underwent surgery for acute appendicitis between 2017 and 2021. Patients were divided into groups based on the time slot in which surgery was performed: morning (8:00 h-15:00 h), afternoon (15:00 h-22:00 h) and night (22:00 h-08:00 h). Demographics, intraoperative data, length of hospital stay, and postoperative complications were analyzed and compared. RESULTS: A total of 1643 patients were included: 337 were operated in the morning, 751 in the afternoon and 555 at night. We found no demographic differences. When comparing the intraoperative data, no differences were observed in the percentage of complicated appendicitis. Night group patients presented a higher percentage of open appendectomies (64.5%) when compared to afternoon (49.6%) and morning (46.2%) groups (p < 0.001). Surgery time was also significantly shorter in the night group (45.2 min ± 18.9 min) (p < 0.001). There were no differences in length of hospital stay, postoperative complications rate or readmission rate. CONCLUSION: These results show that in our institution time slot in which the appendectomy is performed has no consequences in postoperative outcomes and complications.

Predicting carcass tissue composition in Blackbelly sheep using ultrasound measurements and machine learning methods.

This study aimed to predict Blackbelly sheep carcass tissue composition using ultrasound measurements and machine learning models. The models evaluated were decision trees, random forests, support vector machines, and multi-layer perceptrons and were used to predict the total carcass bone (TCB), total carcass fat (TCF), and total carcass muscle (TCM). The best model for predicting the three parameters, TCB, TCF, and TCM was random forests, with mean squared error (MSE) of 0.31, 0.33, and 0.53; mean absolute error (MAE) of 0.26, 0.29, and 0.53; and the coefficient of determination (R2) of 0.67, 0.69, and 0.76, respectively. The results showed that machine learning methods from in vivo ultrasound measurements can be used as determinants of carcass tissue composition, resulting in reliable results.

Reproductive performance of hair ewes and rams implanted with melatonin previous to the anestrus season in northwest Mexico.

Ovine reproductive behavior depends on annual photoperiodic cycle and its impact on endogenous melatonin secretion. In this regard, exogenous melatonin administration previous to the physiological anestrus period could modify the reproductive performance of sheep in the northwest of Mexico. Two independent studies were performed to evaluate such hypothesis in hair sheep implanted with melatonin prior to the anestrus season in latitudes 24° and 25° of Mexico. Study 1 involved 15 rams assigned to one of three treatments receiving 0mg (n=5), 18mg (n=5), or 36mg (n=5) of melatonin subcutaneously. Study variables were measured monthly since implantation (d0) and included testosterone concentration, scrotal circumference, mass motility, individual motility, and sperm concentration. Study 2 included 50 ewes assigned to one of two treatments receiving 0mg (n=25) or 18mg (n=25) of melatonin subcutaneously. In ewes, progesterone concentration and the frequency of females in anestrus were measured during the implantation (-30d), as well as at the beginning (0d) and at the end (45d) of the mating period, while pregnancy rate was determined by ultrasonography 45d after. Continuous variables were analyzed using a mixed effects model considering treatment, time, and the treatment by time interaction as fixed effects. Animal nested within treatment was the random effect. Binary variables were analyzed using the chi-square test. In males, melatonin improved testosterone and sperm concentrations (P<0.05), while in females, a 28% higher pregnancy rate was observed in implanted ewes (P<0.05). Therefore, melatonin enhanced reproductive parameters in both sexes and its exogenous administration previous to the anestrus season in northwest Mexico could be more effective in rams.

Matrix Cauterization With Silver Nitrate in the Treatment of Ingrown Toenails in Children: Pilot Study. / [Artículo traducido] Cauterización de la matriz con nitrato de plata para el tratamiento de las uñas encarnadas en los dedos de los pies en niños: estudio piloto.

BACKGROUND: Although partial onychectomy with chemical matricectomy has been described asthe treatment of choice, there is sparse evidence in the literature regarding the use of silvernitrate for matricectomy. Our aim is to describe the effectiveness of silver nitrate for matrixcauterization after partial onychectomy. METHODS: A prospective observational study was performed on patients with ingrown toenailsstage 2-3 who underwent partial onychectomy with silver nitrate chemical matricectomy during 2018-2019 in our institution. All patients were evaluated in the outpatient clinic on the 7th and 30th post-operative day and a telephone evaluation was performed every 6 months afterthe surgical procedure to date. RESULTS: One hundred and twenty-three patients, who underwent 231 partial onychectomies with silver nitrate chemical matricectomy were included, with a median follow-up of 21 months (interquartile range, 12-29). The procedure had an effectiveness of 95.3%, with only 11 recur-rences (4.7%) reported so far on follow-up. Postoperative infections were observed in 4 patients (1.7%). Adverse effects, such as pain and postoperative drainage, were irrelevant in mostpatients. CONCLUSIONS: Silver nitrate matricectomy after partial onychectomy is an effective and safealternative for the treatment of ingrown toenail in children, with scarce postoperative morbidityand low recurrence rate.

Matrix Cauterization With Silver Nitrate in the Treatment of Ingrown Toenails in Children: Pilot Study.

BACKGROUND: Although partial onychectomy with chemical matricectomy has been described as the treatment of choice, there is sparse evidence in the literature regarding the use of silver nitrate for matricectomy. Our aim is to describe the effectiveness of silver nitrate for matrix cauterization after partial onychectomy. METHODS: A prospective observational study was performed on patients with ingrown toenails stage 2-3 who underwent partial onychectomy with silver nitrate chemical matricectomy during 2018-2019 in our institution. All patients were evaluated in the outpatient clinic on the 7th and 30th post-operative day and a telephone evaluation was performed every 6 months after the surgical procedure to date. RESULTS: One hundred and twenty-three patients, who underwent 231 partial onychectomies with silver nitrate chemical matricectomy were included, with a median follow-up of 21 months (interquartile range, 12-29). The procedure had an effectiveness of 95.3%, with only 11 recurrences (4.7%) reported so far on follow-up. Postoperative infections were observed in 4 patients (1.7%). Adverse effects, such as pain and postoperative drainage, were irrelevant in most patients. CONCLUSIONS: Silver nitrate matricectomy after partial onychectomy is an effective and safe alternative for the treatment of ingrown toenail in children, with scarce postoperative morbidity and low recurrence rate.

Robust Nonequilibrium Edge Currents with and without Band Topology.

We study two-dimensional bosonic and fermionic lattice systems under nonequilibrium conditions corresponding to a sharp gradient of temperature imposed by two thermal baths. In particular, we consider a lattice model with broken time-reversal symmetry that exhibits both topologically trivial and nontrivial phases. Using a nonperturbative Green function approach, we characterize the nonequilibrium current distribution in different parameter regimes. For both bosonic and fermionic systems, we find chiral edge currents that are robust against coupling to reservoirs and to the presence of defects on the boundary or in the bulk. This robustness not only originates from topological effects at zero temperature but, remarkably, also persists as a result of dissipative symmetries in regimes where band topology plays no role. Chirality of the edge currents implies that energy locally flows against the temperature gradient without any external work input. In the fermionic case, there is also a regime with topologically protected boundary currents, which nonetheless do not circulate around all system edges.

Artificial urinary sphincter in congenital neuropathic bladder: Very long-term outcomes.

OBJECTIVE: Artificial urinary sphincter has been used to treat urinary incontinence in children with neuropathic bladder, although there are few studies reporting very long-term results. We assess our experience over the last 27 years in the management of artificial urinary sphincter. METHODS: A retrospective study was performed in patients with neuropathic bladder in whom an artificial urinary sphincter was placed in our institution between 1994 and 2020. Demographic variables, pre- and post-artificial urinary sphincter implantation urodynamic studies, long-term outcomes, and postoperative complications were collected. RESULTS: An artificial urinary sphincter was implanted in 71 patients (median age 14.5; interquartile range 12.8-15.9), with a median follow-up time of 17.2 years (interquartile range 9.8-23.9 years). Thirty-nine patients underwent enterocystoplasty combined with artificial urinary sphincter placement and 32 underwent artificial urinary sphincter implantation alone, of whom 12 patients (16.9%) eventually required an enterocystoplasty because of unexpected bladder behavior changes, usually within 3 years of artificial urinary sphincter implantation. Adequate urinary continence was reported in 90.1% of patients, nine void their bladders spontaneously, and 62 need clean intermittent catheterization. Eighteen mechanical malfunctions occurred in 15 patients (21.1%), with an average artificial urinary sphincter working life of 15.1 ± 1.3 years. In five patients artificial urinary sphincter was removed due to infection or erosion. In 12 patients (30.8%), a continent catheterizable stoma was made (before or during the follow-up) because of problems with clean intermittent catheterization through the urethra. CONCLUSION: The very long-term results of this study demonstrate that artificial urinary sphincter is an effective treatment for urinary incontinence in neuropathic bladder patients. Long-term follow-up is important to identify potential unexpected changes in bladder behavior in these patients.

Robotic Soave pull-through procedure for Hirschsprung's disease in children under 12-months: long-term outcomes.

PURPOSE: To describe the long-term outcomes of the robotic Soave pull-through (RSPT) procedure for Hirschsprung's disease (HSCR) in children younger than 12 months. METHODS: A prospective observational study was conducted on HSCR patients under 12 months of age who underwent RSPT at our institution between 2011 and 2020. Data regarding demographics, clinical features, technical details, operative time, hospital stay, postoperative complications, and long-term outcomes were prospectively collected. RESULTS: A total of 15 patients (9 male; 6 female) were included, with a median age at surgery of 4 months (interquartile range 3-6), and a mean weight of 6.8 ± 1.3 kg. Twelve patients suffered from rectosigmoid aganglionosis and three from long HSCR (extending up to the hepatic flexure). The mean total operative time was 240 ± 72 min. The median hospital stay was 3 days (interquartile range 3-4). Partial anastomosis dehiscence was observed in one patient, requiring reoperation on the 4th postoperative day. With a median follow-up of 79 months (interquartile range 45-115), no fecal incontinence or mild soiling were observed. Constipation occurred in two patients and mild enterocolitis in one case. CONCLUSION: RSPT procedure for Hirschsprung's disease in children younger than 12 months is a safe and effective procedure, with few complications and satisfactory long-term continence outcomes.

Venous malformations: what do phleboliths tell us in the pediatric population?

PURPOSE: Phleboliths are often observed within Venous malformations (VM) and frequently indicated as cause of morbidity. The aim of this study is to investigate independent risk factors for phleboliths in a pediatric population and to determine if its presence influences clinical management. METHODS: We retrospectively review data from patients diagnosed with VM in a vascular anomalies center during a 5-year period. Associations between phleboliths and potential risk factors were assessed. A multivariable analysis, was performed to assess the influence of phleboliths in the need for surgery. RESULTS: We included 88 patients with a mean age of 10 years. Phleboliths were found in 33.0%. In univariate analysis, there were no significant differences between the two groups regarding age or gender, location, dimension or depth of the VM, pain and laboratory parameters. Multivariable analysis could not detect any independent risk factor for phleboliths. In contrast, multivariable logistic analysis revealed that when phleboliths were present, the need for surgical extirpation was more likely (p = 0.031). CONCLUSIONS: This study showed that patients who have phleboliths within their VM seem to require surgery more frequently. This constitutes an entirely innovative thought that could raise awareness to a lower threshold for surgery in this group of patients.

Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients.

Recently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3' massive analysis of cDNA ends (3'MACE). We found >30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-ß-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/ß-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients.

Screen-detected breast cancer is associated with better prognosis and survival compared to self-detected/symptomatic cases in a Chilean cohort of female patients.

PURPOSE: The implementation of national breast cancer (BC) screening programs in Latin America has been rather inconsistent. Instead, most countries have opted for "opportunistic" mammogram screenings on the population at risk. Our study assessed and compared epidemiological, clinical factors, and survival rates associated with BC detected by screening (SDBC) or self-detected/symptomatic (non-SDBC) in Chilean female patients. METHODS: Registry-based cohort study that included non-metastatic BC (stage I/II/III) patients diagnosed between 1993 and 2020, from a public hospital (PH) and a private university cancer center (PC). Epidemiological and clinical data were obtained from medical records. RESULTS: A total of 4559 patients were included. Most patients (55%; n = 2507) came from PH and were diagnosed by signs/symptoms (non-SDBC; n = 3132, 68.6%); these patients displayed poorer overall (OS) and invasive disease-free survival (iDFS) compared to SDBC. Importantly, the proportion of stage I and "luminal" BC (HR + /HER2 -) were significantly higher in SDBC vs. non-SDBC. Finally, using a stage/subset-stratified age/insurance-adjusted model, we found that non-SDBC cases are at a higher risk of death (HR:1.75; p < 0.001). In contrast, patients with PC health insurance have a lower risk of death (HR: 0.60; p < 0.001). CONCLUSION: We confirm previous studies that report better prognosis/survival on SDBC patients. This is probably due to a higher proportion of stage I and luminal-A cases versus non-SDBC. In turn, the survival benefit observed in patients with PC health insurance might be attributed to a larger proportion of SDBC. Our data support the implementation of a systematic BC screening program in Chile to improve patient prognosis and survival rates.

A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer.

BACKGROUND: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3-4 toxicity. METHODS: Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. RESULTS: Reported grade ≤ 2 and 3-4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70-10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19-1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. CONCLUSION: Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.

Quality assessment of environmental water by a simple and fast non-ionic hydrophobic natural deep eutectic solvent-based extraction procedure combined with liquid chromatography tandem mass spectrometry for the determination of plastic migrants.

A non-ionic hydrophobic natural deep eutectic solvent (HNADES) based on thymol and menthol was proposed for the liquid-liquid microextraction of fourteen phthalates and one adipate from environmental water samples. Separation, identification, and quantification were achieved by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. The main factors affecting the extraction efficiency were thoroughly studied. Sample pH of 8 and 100 µL of thymol:menthol at molar ratio 2:1 were selected as the best conditions, while ionic strength and type of dispersant solvent were not relevant for the extraction of the target compounds. The whole methodology was validated for treated wastewater, runoff, and pond water matrices, using di-n-butyl phthalate-3,4,5,6-d4 and dihexyl phthalate-3,4,5,6-d4 as surrogates. Recovery ranged from 70 to 127% with relative standard deviation values lower than 14%. Limits of quantification of the method were in the range 0.042-0.425 µg/L for treated wastewater, 0.015-0.386 µg/L for runoff, and 0.013-0.376 µg/L for pond water. The methodology was applied for the analysis of real treated wastewater, runoff, and pond water samples from different places of Tenerife and Gran Canaria (Canary Islands) finding the presence of diethyl phthalate, diallyl phthalate, dipropyl phthalate, benzylbutyl phthalate, di-n-butyl phthalate, bis-(2-n-butoxyethyl) phthalate, di-n-pentyl phthalate, dicyclohexyl phthalate, and bis-(2-ethylhexyl) phthalate at concentrations between 105.2 and 3414 ng/L.