Prospective validation of the nutrition screening tool for childhood cancer (SCAN).

BACKGROUND & AIMS: Different nutritional screening tools have been proposed in childhood cancer, but none has shown convincing predictive capacity so far. The "nutrition screening tool for childhood cancer (SCAN)" has been specifically designed for this population and provides an easy-to-use, promising approach to identify patients at risk of malnutrition. We aim to: 1. Validate the SCAN tool prospectively in identifying malnourished patients or those who required nutritional support 2. Validate the SCAN tool prospectively in predicting toxicities or outcome. 3. Compare performance of a pediatric screening tool (STRONGKIDS) with SCAN. METHODS: Children in our center with a new diagnosis of cancer from August 2018 to May 2019 were offered to participate in the study. Measurements (SCAN questionnaire, weight, height, body-mass index (BMI), and mid upper-arm circumference (MUAC)) were taken at diagnosis and at regular intervals throughout therapy. The last measurement was taken 6 months after finishing the intensive treatment phase. SCAN score at diagnosis was validated prospectively against variables of interest. RESULTS: A total of 49 patients were recruited. When considering malnutrition during therapy the SCAN tool showed a sensitivity of 37.5% and negative predictive value (NPV) of 81%. Patients who required nutritional support were identified with a sensitivity of 50% and NPV of 62%. The SCAN tool was not able to predict increased toxicities, risk of relapse or decreased survival. The pediatric screening tool STRONGKIDS was unable to discriminate nutritional risk and labeled all 49 patients (100%) as medium or high-risk. Applying SCAN periodically during therapy increased sensitivity for identifying malnutrition to 87.5%. CONCLUSIONS: In our study, applying the SCAN tool at diagnosis showed low sensitivity in identifying patients who go on to develop malnutrition during therapy. However, patients labeled as "not at risk" were unlikely to need nutritional support in the form of nasogastric tube or total parenteral nutrition. Using SCAN throughout therapy could be helpful in building awareness for malnutrition and successfully discriminates between patients who need further support and those who don't.

Effectiveness of Therapeutic Exercise for Children Undergoing Treatment for Cancer: A Systematic Review: Therapeutic Exercise Children Cancer.

PURPOSE: To evaluate the effectiveness of therapeutic physical exercise (TPE) interventions on the physical functioning, psychosocial well-being, and quality of life (QoL) of children undergoing treatment for cancer. METHOD: Systematic review: databases were searched in April 2023. Selection criteria: children (<18 years old) undergoing treatment for cancer or a malignant neoplasm, randomized controlled trial design, utilization of TPE, and including physical and psychosocial outcomes. Internal validity was measured with Physiotherapy Evidence Database scale. RESULTS: Seven randomized controlled trials were included. Most studies showed that strength, fatigue, and QoL improved after the intervention. Cardiorespiratory capacity through 6-minute walk test and physical activity levels were better in the experimental groups. No changes were noted in other variables. CONCLUSIONS: This review supports the importance of a TPE program during cancer treatment, with the aim of maintaining physical capacities and counteracting physical inactivity.

Complications and adverse events in lymphadenectomy of the inguinal area: worldwide expert consensus.

BACKGROUND: Inguinal lymph node dissection plays an important role in the management of melanoma, penile and vulval cancer. Inguinal lymph node dissection is associated with various intraoperative and postoperative complications with significant heterogeneity in classification and reporting. This lack of standardization challenges efforts to study and report inguinal lymph node dissection outcomes. The aim of this study was to devise a system to standardize the classification and reporting of inguinal lymph node dissection perioperative complications by creating a worldwide collaborative, the complications and adverse events in lymphadenectomy of the inguinal area (CALI) group. METHODS: A modified 3-round Delphi consensus approach surveyed a worldwide group of experts in inguinal lymph node dissection for melanoma, penile and vulval cancer. The group of experts included general surgeons, urologists and oncologists (gynaecological and surgical). The survey assessed expert agreement on inguinal lymph node dissection perioperative complications. Panel interrater agreement and consistency were assessed as the overall percentage agreement and Cronbach's α. RESULTS: Forty-seven experienced consultants were enrolled: 26 (55.3%) urologists, 11 (23.4%) surgical oncologists, 6 (12.8%) general surgeons and 4 (8.5%) gynaecology oncologists. Based on their expertise, 31 (66%), 10 (21.3%) and 22 (46.8%) of the participants treat penile cancer, vulval cancer and melanoma using inguinal lymph node dissection respectively; 89.4% (42 of 47) agreed with the definitions and inclusion as part of the inguinal lymph node dissection intraoperative complication group, while 93.6% (44 of 47) agreed that postoperative complications should be subclassified into five macrocategories. Unanimous agreement (100%, 37 of 37) was achieved with the final standardized classification system for reporting inguinal lymph node dissection complications in melanoma, vulval cancer and penile cancer. CONCLUSION: The complications and adverse events in lymphadenectomy of the inguinal area classification system has been developed as a tool to standardize the assessment and reporting of complications during inguinal lymph node dissection for the treatment of melanoma, vulval and penile cancer.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.

Immune checkpoint blockade has changed the treatment paradigm for advanced solid tumors, but the overall response rates are still limited. The combination of checkpoint blockade with anti-4-1BB antibodies to stimulate tumor-infiltrating T cells has shown anti-tumor activity in human trials. However, the further clinical development of these antibodies has been hampered by significant off-tumor toxicities. Here, we generated an anti-4-1BB/EGFR/PD-L1 trispecific antibody consisting of a triple-targeting tandem trimerbody (TT) fused to an engineered silent Fc region. This antibody (IgTT-4E1-S) was designed to combine the blockade of the PD-L1/PD-1 axis with conditional 4-1BB costimulation specifically confined to the tumor microenvironment (TME). The antibody demonstrated simultaneous binding to purified EGFR, PD-L1, and 4-1BB in solution, effective blockade of the PD-L1/PD1 interaction, and potent 4-1BB-mediated costimulation, but only in the presence of EGFR-expressing cells. These results demonstrate the feasibility of IgTT-4E1-S specifically blocking the PD-L1/PD-1 axis and inducing EGFR-conditional 4-1BB agonist activity.

Facial trauma in the major league baseball.

OBJECTIVE: The objectives of this study were to identify and describe significant facial trauma present in Major League Baseball (MLB) that resulted in players missing games or being placed in the injury reserve list. STUDY DESIGN: This was a retrospective cohort study. The predictor variables were the player's age, height, weight, body mass index, position, team conference, and if played games took place in playoffs season. The outcome variables were injury location (upper, middle, and lower facial third) and type of injury (soft tissue, fracture). Chi-square and logistic regression were computed to determine associations between predictor and outcome variables. RESULTS: A total of 109 players missed games due to facial injuries, and a total of 115 injuries were identified. Of the 115 injuries, none occurred in the upper facial third, 96 (83%) were in the middle third, and 19 (17%) in the lower third. Most fractures occurred in fielders (45%), and most soft tissue injuries in basemen (40%). CONCLUSIONS: Significant facial trauma in the MLB has risen in recent years. The player's height, conference, and playoff season were the most associated factors. Most injuries occurred in the periorbital area. A recommendation for the use of protection goggles can be made to prevent them.

Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo.

Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)-directed immunotherapy, including T cells bearing chimeric antigen receptors (CARs) and systemically injected bispecific T cell engagers (TCEs), has shown remarkable clinical activity, and several products have received market approval. However, despite promising results, most patients eventually become refractory and relapse, highlighting the need for alternative strategies. Engineered T cells secreting TCE antibodies (STAb) represent a promising strategy that combines the advantages of adoptive cell therapies and bispecific antibodies. Here, we undertook a comprehensive preclinical study comparing the therapeutic potential of T cells either expressing second-generation anti-BCMA CARs (CAR-T) or secreting BCMAxCD3 TCEs (STAb-T) in a T cell-limiting experimental setting mimicking the conditions found in patients with relapsed/refractory multiple myeloma. STAb-T cells recruited T cell activity at extremely low effector-to-target ratios and were resistant to inhibition mediated by soluble BCMA released from the cell surface, resulting in enhanced cytotoxic responses and prevention of immune escape of multiple myeloma cells in vitro. These advantages led to robust expansion and persistence of STAb-T cells in vivo, generating long-lived memory BCMA-specific responses that could control multiple myeloma progression in xenograft models, outperforming traditional CAR-T cells. These promising preclinical results encourage clinical testing of the BCMA-STAb-T cell approach in relapsed/refractory multiple myeloma.

Nickel-based cerium zirconate inorganic complex structures for CO2 valorisation via dry reforming of methane.

The increasing anthropogenic emissions of greenhouse gases (GHG) is encouraging extensive research in CO2 utilisation. Dry reforming of methane (DRM) depicts a viable strategy to convert both CO2 and CH4 into syngas, a worthwhile chemical intermediate. Among the different active phases for DRM, the use of nickel as catalyst is economically favourable, but typically deactivates due to sintering and carbon deposition. The stabilisation of Ni at different loadings in cerium zirconate inorganic complex structures is investigated in this work as strategy to develop robust Ni-based DRM catalysts. XRD and TPR-H2 analyses confirmed the existence of different phases according to the Ni loading in these materials. Besides, superficial Ni is observed as well as the existence of a CeNiO3 perovskite structure. The catalytic activity was tested, proving that 10 wt.% Ni loading is the optimum which maximises conversion. This catalyst was also tested in long-term stability experiments at 600 and 800°C in order to study the potential deactivation issues at two different temperatures. At 600°C, carbon formation is the main cause of catalytic deactivation, whereas a robust stability is shown at 800°C, observing no sintering of the active phase evidencing the success of this strategy rendering a new family of economically appealing CO2 and biogas mixtures upgrading catalysts.

Association of race and ethnicity with initial surgical hemodialysis access type in a safety net system.

OBJECTIVES: Prior studies have found lower arteriovenous fistula (AVF) creation rates in Black and Hispanic patients. Whether this is due to health care disparities or other differences is unclear. Our objective was to evaluate the racial/ethnic differences in initial surgical access type within a high-volume, safety net system with predominantly Black and Hispanic populations. METHODS: A retrospective review of initial hemodialysis (HD) access in consecutive cases between 2014 and 2019 was conducted from all five safety net hospitals in a health care system that primarily treats underserved patients. Patient data collected included race, ethnicity, sex, comorbidities, and initial arteriovenous (AV) access type (AV fistula [AVF] vs AV graft [AVG]). The rates of cephalic vein-based AVF (CAVF; radiocephalic, brachiocephalic) were compared with basilic and brachial vein AVF (BAVF), because the latter are performed as two stages. Bivariate and multivariate logistic regression models were adjusted for demographic and clinical variables to evaluate the relationship between race/ethnicity, surgical access type, and comorbid conditions. RESULTS: We included 1334 patients (74% Hispanic, 9% Black, 7% Asian, 2% White, 8% other) who underwent first-time surgical HD access creation. The majority were male (818 [63%]). Medical comorbidities were equal among groups, except for chronic obstructive pulmonary disease and stroke, which were higher in Black patients (P < .005 and P = .005, respectively). Overall, 1303 patients (98%) underwent AVF creation and 31 AVG creation (2%), with no difference between race/ethnicity in AVF vs AVG creation. Of the AVF cohort, 991 (76%) had a CAVF and 312 (24%) had a BAVF. Males were more likely than females to get a CAVF (65% vs 35%; P = .002). CONCLUSIONS: Within our safety net health system, where most patients are under-represented minorities, nearly all patients undergoing HD access had an AVF as their initial surgery with no difference in race/ethnicity. AVF type received differed by race, with Black patients twice as likely to undergo BAVF, which required two stages. Further studies are needed to identify the reasons for these differences.

HeNeCOn: An ontology for integrative research in Head and Neck cancer.

BACKGROUND: Head and Neck Cancer (HNC) has a high incidence and prevalence in the worldwide population. The broad terminology associated with these diseases and their multimodality treatments generates large amounts of heterogeneous clinical data, which motivates the construction of a high-quality harmonization model to standardize this multi-source clinical data in terms of format and semantics. The use of ontologies and semantic techniques is a well-known approach to face this challenge. OBJECTIVE: This work aims to provide a clinically reliable data model for HNC processes during all phases of the disease: prognosis, treatment, and follow-up. Therefore, we built the first ontology specifically focused on the HNC domain, named HeNeCOn (Head and Neck Cancer Ontology). METHODS: First, an annotated dataset was established to provide a formal reference description of HNC. Then, 170 clinical variables were organized into a taxonomy, and later expanded and mapped to formalize and integrate multiple databases into the HeNeCOn ontology. The outcomes of this iterative process were reviewed and validated by clinicians and statisticians. RESULTS: HeNeCOn is an ontology consisting of 502 classes, a taxonomy with a hierarchical structure, semantic definitions of 283 medical terms and detailed relations between them, which can be used as a tool for information extraction and knowledge management. CONCLUSION: HeNeCOn is a reusable, extendible and standardized ontology which establishes a reference data model for terminology structure and standard definitions in the Head and Neck Cancer domain. This ontology allows handling both current and newly generated knowledge in Head and Neck cancer research, by means of data linking and mapping with other public ontologies.

Interrupciones voluntarias del embarazo recurrentes. Estudio de prevalencia y exploración de factores asociados. Antioquia, Colombia, 2015 - 2021 / Recurrent voluntary termination of pregnancy. Prevalence study and exploration of associated factors. Antioquia, Colombia, 2015 ­ 2021

Objetivos: Describir la prevalencia de las interrupciones voluntarias del embarazo (IVE) recurrentes y efectuar una exploración de los factores asociados a esta. Materiales y métodos: Estudio de corte trasversal descriptivo, en el que se incluyeron mujeres atendidas entre 2015 y 2021 en cinco sedes, en el Departamento de Antioquia, de una Institución que promueve la atención en salud sexual y reproductiva (SSR) en Colombia. Se midieron variables sociodemográficas, de SSR, así como la realización de IVE recurrente, tipo de procedimiento utilizado en la primera IVE, y método de anticoncepción elegido posterior a esta. Se presenta la prevalencia de período de aborto recurrente global y por año. Se hace exploración de los factores asociados por medio de análisis multivariado. Se obtuvo aval del comité de investigación de la institución. Resultados: Se incluyó un total de 20.423 mujeres. La prevalencia de IVE recurrente fue del 4,07 % (n = 831) en todo el período, y varió del 2,3 al 6 % en los 6 años. El método más utilizado para la IVE recurrente fue inducción farmacológica (48,50 %). Después de la primera IVE, el 69,81 % de las mujeres utilizó métodos anticonceptivos clasificados como "muy efectivos", según la Organización Mundial de la Salud. Se identificaron como factores de riesgo de la IVE recurrente pertenecer al régimen de aseguramiento subsidiado por el Estado (Odds ratio ajustado (ORa) = 1,35; IC 95 %: 1,05-1,72) y haber tenido dos o más gestaciones (ORa = 1,23; IC 95 %: 1,06 - 1,44). Como factores protectores se identificaron: contratación del servicio de IVE bajo modalidad de pago de bolsillo (ORa = 0,71; IC 95 %: 0,61-0,82), el antecedente de IVE tardía (ORa = 0,30; IC 95 %: 0,11-0,81), y la elección del implante subdérmico posterior al primer aborto primer aborto como (ORa =0,64; IC 95 %: 0,49 - 0,83). Conclusiones: La prevalencia de IVE recurrente posiblemente está incrementando. Se requieren estudios prospectivos que evalúen si existe una tendencia al incremento y que verifiquen posibles hipótesis de asociación que surgen de este trabajo.

Objectives: To describe the prevalence of recurrent voluntary termination of pregnancy (VTP) and to explore associated factors. Material and methods: Descriptive, cross-sectional cohort study which included women seen between 2015 and 2021 in five sites of an institution located in the Department of Antioquia which promotes sexual and reproductive health (SRH) care in Colombia. Measured variables included sociodemographics, SRH, recurrent performance of VTP, type of procedure used in the first VTP and contraception method selected afterwards. The prevalence of global and yearly recurrent abortion period is presented. Associated factors were explored using a multivariate analysis. The research committee of the institution approved the study. Results: In total, 20,423 women were included. The prevalence of recurrent VTP was 4.07 % (n = 831) during the entire period, ranging between 2.3 and 6 % over the 7 years. The most commonly used method for recurrent VTP was pharmacological induction (48.50 %). After the first VTP, 69.81 % of women used contraceptive methods classified as "very effective" according to the World Health Organization. The risk factors identified as being associated with recurrent VTP included being part of the state-subsidized health insurance system (adjusted odds ratio [aOR] = 1.35; 95 % CI:1.05-1.72) and having had two or more pregnancies (aOR = 1.23; 95% CI: 1.06 - 1.44). Protective factors were identified and included out-of-pocket payment for VTP service (aOR = 0.71; 95% CI: 0.61-0.82), a history of late VTP (aOR = 0.30; 95% CI: 0.11-0.81), and the selection of a subdermal implant for contraception following the first abortion (sOR = 0.64; 95% CI: 0.49 - 0.83). Conclusions: It is possible that the prevalence of recurrent VTP is increasing. Prospective studies are required in order to determine whether there is a growing trend and to verify potential association hypotheses derived from this work.

Portal hypertension increases the risk of hepatic decompensation after 90Yttrium radioembolization in patients with hepatocellular carcinoma: a cohort study.

Background: Transarterial radioembolization (TARE) is increasingly used in patients with hepatocellular carcinoma (HCC). This treatment can induce or impair portal hypertension, leading to hepatic decompensation. TARE also promotes changes in liver and spleen volumes that may modify therapeutic decisions and outcomes after therapy. Objectives: We aimed to investigate the impact of TARE on the incidence of decompensation events and its predictive factors. Design: In all, 63 consecutive patients treated with TARE between February 2012 and December 2018 were retrospectively included. Methods: We assessed clinical (including Barcelona Clinic Liver Cancer stage, portal hypertension assessment, and liver decompensation), laboratory parameters, and liver and spleen volumes before and 6 and 12 weeks after treatment. A multivariate analysis was performed. Results: In total, 18 out of 63 (28.6%) patients had liver decompensation (ascites, variceal bleeding, jaundice, or encephalopathy) within the first 3 months after therapy, not associated with tumor progression. Clinically significant portal hypertension (CSPH) and bilobar treatment independently predicted the development of liver decompensation after TARE. A significant volume increase in the non-treated hemi-liver was observed only in patients with unilobar treatment (median volume increase of 20.2% in patients with right lobe TARE; p = 0.007), especially in those without CSPH. Spleen volume also increased after TARE (median volume increase of 16.1%; p = 0.0001) and was associated with worsening liver function scores and decreased platelet count. Conclusion: Bilobar TARE and CSPH may be associated with an increased risk of liver decompensation in patients with intermediate or advanced HCC. A careful assessment considering these variables before therapy may optimize candidate selection and improve treatment planning.

Hepatotoxic Evaluation of N-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer.

Valproic acid (VPA) is a drug that has various therapeutic applications; however, it has been associated with liver damage. Furthermore, it is interesting to propose new compounds derived from VPA as N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA has better antiproliferative activity than the VPA in different cancer cell lines. The purpose of this study was to evaluate the liver injury of HO-AAVPA by acute treatment (once administration) and repeated doses for 7 days under intraperitoneal administration. The median lethal dose value (LD50) was determined in rats and mice (females and males) using OECD Guideline 425. In the study, male rats were randomly divided into 4 groups (n = 7), G1: control (without treatment), G2: vehicle, G3: VPA (500 mg/kg), and G4: HO-AAVPA (708 mg/kg, in equimolar ratio to VPA). Some biomarkers related to hepatotoxicity were evaluated. In addition, macroscopic and histological studies were performed. The LD50 value of HO-AAVPA was greater than 2000 mg/kg. Regarding macroscopy and biochemistry, the HO-AAVPA does not induce liver injury according to the measures of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutathione peroxidase, glutathione reductase, and catalase activities. Comparing the treatment with HO-AAVPA and VPA did not show a significant difference with the control group, while malondialdehyde and glutathione-reduced levels in the group treated with HO-AAVPA were close to those of the control (p ≤ 0.05). The histological study shows that liver lesions caused by HO-AAVPA were less severe compared with VPA. Therefore, it is suggested that HO-AAVPA does not induce hepatotoxicity at therapeutic doses, considering that in the future it could be proposed as an antineoplastic drug.

Clinical Findings and Genetic Analysis of Nine Mexican Families with Bartter Syndrome.

BACKGROUND: Bartter's syndrome (BS) is a group of salt-wasting tubulopathies characterized by hypokalemia, metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism, and low or normal blood pressure. Loss-of-function variants in genes encoding for five proteins expressed in the thick ascending limb of Henle in the nephron, produced different genetic types of BS. AIM: Clinical and genetic analysis of families with Antenatal Bartter syndrome (ABS) and with Classic Bartter syndrome (CBS). METHODS: Nine patients from unrelated non-consanguineous Mexican families were studied. Massive parallel sequencing of a gene panel or whole-exome sequencing was used to identify the causative gene. RESULTS: Proband 1 was homozygous for the pathogenic variant p.Arg302Gln in the SLC12A1 gene encoding for the sodium-potassium-chloride NKCC2 cotransporter. Proband 3 was homozygous for the nonsense variant p.Cys308* in the KCNJ1 gene encoding for the ROMK potassium channel. Probands 7, 8, and 9 showed variants in the CLCKNB gene encoding the chloride channel ClC-Kb: proband 7 was compound heterozygous for the deletion of the entire gene and the missense change p.Arg438Cys; proband 8 presented a homozygous deletion of the whole gene and proband 9 was homozygous for the nonsense mutation p.Arg595*. A heterozygous variant of unknown significance was detected in the SLC12A1 gene in proband 2, and no variants were found in SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, and MAGED2 genes in probands 4, 5, and 6. CONCLUSIONS: Genetic analysis identified loss-of-function variants in the SLC12A1, KCNJ1, and CLCNKB genes in four patients with ABS and in the CLCNKB gene in two patients with CBS.

An Integral Approach to the Molecular Diagnosis of Tuberous Sclerosis Complex: The Role of Mosaicism and Splicing Variants.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the presence of hamartomas in multiple organs. At the molecular level, the disease is caused by pathogenic variants in the TSC1 and TSC2 genes, and only 10% to 25% of clinically diagnosed patients remain negative after multiplex ligation-dependent probe amplification and exon sequencing of both genes. Here, to improve the molecular diagnosis of TSC, we developed an integral approach that includes multiplex ligation-dependent probe amplification and deep-coverage next-generation sequencing of the entire TSC1 and TSC2 genes, along with an adapted bioinformatic pipeline to detect variants at low allele frequencies (>1%). Using this workflow, the molecular cause was identified in 29 of 42 patients with TSC, describing here, for the first time, 12 novel pathogenic variants in TSC genes. These variants included seven splicing variants, five of which were studied at the cDNA level, determining their effect on splicing. In addition, 8 of the 29 pathogenic variants were detected in mosaicism, including four patients with previous negative study results who presented extremely low mosaic variants (allele frequency, <16%). We demonstrate that this integral approach allows the molecular diagnosis of patients with TSC and improves the conventional one by adapting the technology to the detection of low-frequency mosaics.

Bibliometric analysis of academic journal recommendations and requirements for surgical and anesthesiologic adverse events reporting.

BACKGROUND: Standards for reporting surgical adverse events (AEs) vary widely within the scientific literature. Failure to adequately capture AEs hinders efforts to measure the safety of healthcare delivery and improve the quality of care. The aim of the present study is to assess the prevalence and typology of perioperative AE reporting guidelines among surgery and anesthesiology journals. MATERIALS AND METHODS: In November 2021, three independent reviewers queried journal lists from the SCImago Journal & Country Rank (SJR) portal (www.scimagojr.com), a bibliometric indicator database for surgery and anesthesiology academic journals. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted from Scopus journal data. Quartile 1 (Q1) was considered the top quartile and Q4 bottom quartile based on the journal impact factor. Journal author guidelines were collected to determine whether AE reporting recommendations were included and, if so, the preferred reporting procedures. RESULTS: Of 1409 journals queried, 655 (46.5%) recommended surgical AE reporting. Journals most likely to recommend AE reporting were: by category surgery (59.1%), urology (53.3%), and anesthesia (52.3%); in top SJR quartiles (i.e. more influential); by region, based in Western Europe (49.8%), North America (49.3%), and the Middle East (48.3%). CONCLUSIONS: Surgery and anesthesiology journals do not consistently require or provide recommendations on perioperative AE reporting. Journal guidelines regarding AE reporting should be standardized and are needed to improve the quality of surgical AE reporting with the ultimate goal of improving patient morbidity and mortality.

Increased Prevalence of Symptomatic Human Intestinal Spirochetosis in MSM with High-Risk Sexual Behavior in a Cohort of 165 Individuals.

Human intestinal spirochetosis (HIS) can cause gastrointestinal symptoms, although asymptomatic infections have been described. Individuals from low-income countries, people living with HIV, and men who have sex with men (MSM) show increased risk. A retrospective review of all patients diagnosed with HIS (n = 165) between January 2013 and October 2020 at a tertiary hospital in Madrid, Spain, was performed to assess risk factors for symptomatic HIS, symptoms, and response to treatment. Most patients were male (n = 156; 94.5%), 86.7% were MSM, and 23.5% practiced chemsex, of whom most were symptomatic (p = 0.039). Most patients (78.4%) reported unprotected oral-anal intercourse. A total of 124 (81.1%) were symptomatic; diarrhea was the most common complaint (68.3%). Multivariable regression showed increased odds of symptoms associated with age under 41 (odds ratio 5.44, 95% CI 1.87-15.88; p = 0.002). Colonoscopy was normal in 153 (92.7%). Furthermore, 66.7% presented previous or concomitant sexually transmitted diseases (STDs). Among the patients, 102 underwent testing for other gastrointestinal pathogens, with positive results in 20 (19.6%). All symptomatic patients without concomitant gastrointestinal infection presenting improvement on follow-up (42 of 53) had received either metronidazole or doxycycline (p = 0.049). HIS should be considered as a cause of chronic diarrhea in MSM with high-risk sexual behavior after other causes have been ruled out; treatment with metronidazole is recommended. Coinfection with other STDs is common.

Severity Grading Systems for Intraoperative Adverse Events. A Systematic Review of the Literature and Citation Analysis.

INTRODUCTION: The accurate assessment and grading of adverse events (AE) is essential to ensure comparisons between surgical procedures and outcomes. The current lack of a standardized severity grading system may limit our understanding of the true morbidity attributed to AEs in surgery. The aim of this study is to review the prevalence in which intraoperative adverse event (iAE) severity grading systems are used in the literature, evaluate the strengths and limitations of these systems, and appraise their applicability in clinical studies. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. PubMed, Web of Science, and Scopus were queried to yield all clinical studies reporting the proposal and/or the validation of iAE severity grading systems. Google Scholar, Web of Science, and Scopus were searched separately to identify the articles citing the systems to grade iAEs identified in the first search. RESULTS: Our search yielded 2957 studies, with 7 studies considered for the qualitative synthesis. Five studies considered only surgical/interventional iAEs, while 2 considered both surgical/interventional and anesthesiologic iAEs. Two included studies validated the iAE severity grading system prospectively. A total of 357 citations were retrieved, with an overall self/nonself-citation ratio of 0.17 (53/304). The majority of citing articles were clinical studies (44.1%). The average number of citations per year was 6.7 citations for each classification/severity system, with only 2.05 citations/year for clinical studies. Of the 158 clinical studies citing the severity grading systems, only 90 (56.9%) used them to grade the iAEs. The appraisal of applicability (mean%/median%) was below the 70% threshold in 3 domains: stakeholder involvement (46/47), clarity of presentation (65/67), and applicability (57/56). CONCLUSION: Seven severity grading systems for iAEs have been published in the last decade. Despite the importance of collecting and grading the iAEs, these systems are poorly adopted, with only a few studies per year using them. A uniform globally implemented severity grading system is needed to produce comparable data across studies and develop strategies to decrease iAEs, further improving patient safety.

Urticaria after breakthrough Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 infection in a triple-vaccinated (Pfizer) patient: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 continues to threaten public health. The virus is causing breakthrough infections in vaccinated individuals. Also, scarce information is available about cutaneous manifestations after severe acute respiratory syndrome coronavirus 2 infection. CASE PRESENTATION AND FINDINGS: A case of a triple-vaccinated (Pfizer) 37-year-old Hispanic American (Colombian) male who developed urticaria after Omicron BA.5.1 severe acute respiratory syndrome coronavirus 2 breakthrough infection is described. Virus isolation and whole genome sequencing along with immune and molecular assays were performed. Dermatological manifestations (skin rash and urticaria) after Omicron BA.5.1 infection were observed. Sequence analysis of the Omicron BA.5.1 isolate also revealed several important mutations. Hemogram analysis revealed leukocytosis and neutrophilia. Serology testing revealed anti-spike immunoglobulin G serum titers but negative detection of immunoglobulin M at 10 days after symptom onset. Anti-nucleocapsid, anti-spike 1 immunoglobulin G, anti-spike trimer, and anti-receptor-binding-domain immunoglobulin G and immunoglobulin E sera were detected at different titers 10 days after symptom onset. Several serum levels of chemokines/cytokines (Interferon-α, interferon-γ, interleukin-12/interleukin-23p40, interleukin-18, interferon gamma-induced protein-10, monocyte chemoattractant protein-1, monokine induced by gamma, macrophage inflammatory protein-1α, chemokine (C-C motif) ligand-5 , tumor necrosis factor-ß1, Tumor necrosis factor-α) were detected, but interleukin-2, interleukin-4, interleukin-6, interleukin-8, and interleukin-17A were below the limit of detection. INTERPRETATION AND CONCLUSIONS: To our knowledge, this is the first study describing skin effects of a severe acute respiratory syndrome coronavirus 2 Omicron BA.5 variant breakthrough infection in a triple-vaccinated patient in Colombia. Several important mutations were found in the spike glycoprotein of the virus isolated; these mutations are associated with immune evasion and changes in antigenic properties of the virus. Physicians overseeing coronavirus disease 2019 cases should be aware of the potential skin effects of the infection. Pathogenesis of severe acute respiratory syndrome coronavirus 2 infection and its association with proinflammatory cytokines and chemokines may enhance the development of urticaria and other skin manifestations in immunized individuals. However, further studies are needed to better understand the complexity of coronavirus disease in such situations.