Epidemiology and clinical features of Streptococcus pyogenes bloodstream infections in children in Madrid, Spain.

Studies have shown increased invasive Group A Streptococcus (GAS) disease, including bloodstream infections (GAS-BSI). However, the epidemiological data of GAS-BSI are limited in children. We aimed to describe GAS-BSI in children in Madrid, over 13 years (2005-2017). Multicenter retrospective cohort study from 16 hospitals from Madrid, Spain. Epidemiology, symptomatology, laboratory, treatment, and outcome of GAS-BSI in children ≤ 16 years were analyzed. 109 cases of GAS-BSI were included, with incidence rate of 4.3 episodes/100,000 children attended at the emergency department/year. We compared incidence between two periods (P1: 2005-June 2011 vs P2: July 2011-2017) and observed a non-significant increase along the study period (annual percentage change: + 6.0% [95%CI: -2.7, + 15.4]; p = 0.163). Median age was 24.1 months (IQR: 14.0-53.7), peaking during the first four years of life (89/109 cases; 81.6%). Primary BSI (46.8%), skin and soft tissue (21.1%), and osteoarticular infections (18.3%) were the most common syndromes. We compared children with primary BSI with those with a known source and observed that the former had shorter hospital stay (7 vs. 13 days; p = 0.003) and received intravenous antibiotics less frequently (72.5% vs. 94.8%; p = 0.001) and for shorter duration of total antibiotic therapy (10 vs. 21 days; p = 0.001). 22% of cases required PICU admission. Factors associated with severity were respiratory distress, pneumonia, thrombocytopenia, and surgery, but in multivariate analysis, only respiratory distress remained significant (adjusted OR:9.23 [95%CI: 2.16-29.41]). Two children (1.8%) died.   Conclusion: We observed an increasing, although non-significant, trend of GAS-BSI incidence within the study. Younger children were more frequently involved, and primary BSI was the most common and less severe syndrome. PICU admission was frequent, being respiratory distress the main risk factor. What is known: • In recent decades, several reports have shown a worldwide increase in the incidence of invasive Group A streptococcal disease (GAS), including bloodstream infection (BSI). Recently, there have been a few reports showing an increase in severity as well. • There needs to be more information on the epidemiology in children since most studies predominantly include adults. What is new: • This study, carried out in children with GAS-BSI in Madrid, shows that GAS-BSI affects mostly younger children, with a broad spectrum of manifestations, needing PICU admission frequently. Respiratory distress was the leading risk factor for severity, whereas primary BSI seemed to be less severe. • We observed an increasing, although non-significant, trend of GAS-BSI incidence in recent years (2005-2017).

Ultrastaging protocol in sentinel lymph node for apparent early stage ovarian cancer.

OBJECTIVE: The objective of the present study is to determine the role of sentinel lymph node (SLN) ultrastaging in apparent early-stage ovarian cancer. METHODS: We previously demonstrated the feasibility of SLN in early-stage ovarian cancer in a pilot study and in a clinical trial (NCT03452982). The SLN of the 30 patients involved in both were processed following an ultrastaging protocol. The cost of ultrastaging processing was also reported. RESULTS: A SLN was detected in up to 91.3% and 90% in the pelvic and para-aortic region, respectively. In all cases, a SLN was detected at least in one field, pelvic or para-aortic. The mean time from injection to SLN resection was 53.3 ± 20.3 min. Two of 30 (6.6%) patients had a contralateral SLN in the para-aortic field, but no patients had contralateral SLN within the pelvic field after injection. The mean number of harvested SLN was 2.1 ± 1.4 (range: 0-5) and 2.7 ± 1.5 (range: 0-7) in the pelvic and para-aortic region, respectively. Two patients were upgraded to stage IIIA1 because of lymph node metastasis. In the first case, based on single sections and haematoxylin and eosin (H&E) examination, a pelvic SLN micrometastasis (1 mm) was found on the first H&E section. By using the ultrastaging protocol, the size of the metastasis was increased to 2.1 mm (macrometastasis). In the same patient, the ultrastaging study of the inframesenteric para-cava SLNs found isolated tumour cells in the subcapsular and interfollicular lymph nodes sinus in one of the two SLN harvested (in one of the sections at the fourth and fifth ultrastage levels). The other upstaged case was a para-aortic macrometastasis in a patient in whom the SLN was not identified in the para-aortic field because of the absence of migration from the infundibulo-pelvic stump injection. The cost of ultrastaging in each patient depended on the total number of SLN retrieved, averaging 96.8 € (range: 0-230.5) and 124.5 € (range: 0-322.7€) for pelvic and para-aortic SLN, respectively. CONCLUSIONS: A uniform protocol for ultrastaging is essential for lower-volume metastasis detection and to provide reproducible information between upcoming studies, as evidence about SLN in ovarian cancer is growing.

Sentinel lymph node technique in early-stage ovarian cancer (SENTOV): a phase II clinical trial.

OBJECTIVE: Early-stage ovarian cancer might represent an ideal disease scenario for sentinel lymph node application. Nevertheless, the published experience seems to be limited. Our objective was to assess the feasibility and safety concerns of sentinel lymph node biopsy in patients with clinical stage I-II ovarian cancer. METHODS: We conducted a prospective cohort study of 20 patients with histologically confirmed ovarian cancer. 99mTc and indocyanine green were injected into both the utero-ovarian and infundibulopelvic ligament stump, if they were present, during surgical staging. An intraoperative gamma probe and near-infrared fluorescence imaging were used to detect the sentinel lymph nodes. Inclusion criteria included: >18 years of age, suspicious adnexal mass (unilateral or bilateral) at ultrasound and CT imaging or confirmed ovarian tumor after previous surgery (unilateral or bilateral salpingo-oophorectomy with or without hysterectomy). Adverse events were recorded through postoperative day 30. The primary trial end point was to report adverse events related to the technique, including the use of 99mTc and ICG intraperitoneally, as well as the feasibility of the technique. RESULTS: A total of 20 patients were included in the analysis. Sentinel lymph nodes were detected in 14/15 (93%) pelvic and all 20 (100%) para-aortic regions. Five patients did not have utero-ovarian injection because of prior hysterectomy. The mean time from injection to sentinel lymph node resection was 53±15 min (range; 30-80). The mean number of harvested sentinel lymph nodes was 2.2±1.5 (range; 0-5) lymph nodes in the pelvis and 3.3±1.8 (range; 1-7) lymph nodes in the para-aortic region. There were no adverse intraoperative events, nor any within the 30 days of follow-up related with the technique. CONCLUSION: Sentinel lymph node mapping in early-stage ovarian cancer is feasible without major intraoperative or < 30 days safety concerns. (NCT03452982). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03452982.

The differential diagnoses of uterine leiomyomas and leiomyosarcomas using DNA and RNA sequencing.

BACKGROUND: Although uterine leiomyomas and leiomyosarcomas are considered biologically unrelated tumors, they share morphologic and histologic characteristics that complicate their differential diagnosis. The long-term therapeutic option for leiomyoma is laparoscopic myomectomy with morcellation, particularly for patients who wish to preserve their fertility. However, because of the potential dissemination of undiagnosed or hidden leiomyosarcoma from morcellation, there is a need to develop a preoperative assessment of malignancy risk. OBJECTIVE: Through an integrated comparative genomic and transcriptomic analysis, we aim to identify differential genetic targets in leiomyomas vs leiomyosarcomas using next-generation sequencing as the first step toward preoperative differential diagnosis. STUDY DESIGN: Targeted sequencing of DNA and RNA coding regions for solid tumor-associated genes was performed on formalin-fixed paraffin-embedded samples from 13 leiomyomas and 13 leiomyosarcoma cases. DNA sequencing was used to identify copy number variations, single-nucleotide variants, and small insertions/deletions. RNA sequencing was used to identify gene fusions, splice variants, and/or differential gene expression profiles. RESULTS: In leiomyosarcomas, tumor mutation burden was higher in terms of copy number variations, single nucleotide variants, small insertions/deletions, and gene fusions compared with leiomyomas. For copy number variations, 20 genes were affected by deletions in leiomyosarcomas, compared with 6 observed losses in leiomyomas. Gains (duplications) were identified in 19 genes in leiomyosarcomas, but only 3 genes in leiomyomas. The most common mutations (single-nucleotide variants and insertions/deletions) for leiomyosarcomas were identified in 105 genes of all analyzed leiomyosarcomas; 82 genes were affected in leiomyomas. Of note, 1 tumor previously diagnosed as leiomyosarcoma was established as inflammatory myofibroblastic tumor along this study with a novel ALK-TNS1 fusion. Finally, a differential transcriptomic profile was observed for 11 of 55 genes analyzed in leiomyosarcomas; 8.5% of initially diagnosed leiomyosarcomas showed high-confidence, novel gene fusions that were associated with these tumors. CONCLUSION: Through integrated comparative genomic and transcriptomic analyses, we identified novel differential genetic targets that potentially differentiate leiomyosarcomas and leiomyomas. This provides a new insight into the differential diagnosis of these myometrial tumors.

CENTRAL NERVOUS SYSTEM INFECTION BY GROUP A STREPTOCOCCUS IN CHILDREN IN SPAIN (2019-2023).

Central nervous system infections in children caused by group A Streptococcus are rare. This study, conducted across 52 hospitals in Spain from 2019 to 2023, identified 32 cases of central nervous system infections in children caused by group A Streptococcus, with a significant increase from October 2022 onward (1.1% vs. 5.9%, P = 0.002). Half required pediatric intensive care unit admission, 12.5% exhibited sequelae and the mortality rate was 6.2%. Mastoiditis was the predominant primary infection.

One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA).

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 µm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/µL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

Port site resection after laparoscopy in advance ovarian cancer surgery: Time to abandon?

INTRODUCTION: The use of laparoscopy in the treatment and management of advanced ovarian cancer is increasing among the gynaecologic oncologists. The development of port site metastases after laparoscopy is a concern and a matter of debate due to theoretical iatrogenic disease spread. Port site resection (PSR) has been proposed as an option to avoid this scenario. MATERIAL AND METHODS: One hundred and twenty-three patients with advanced ovarian cancer (FIGO III-IV) and with diagnostic laparoscopy were included and after cytoreductive surgery were classified into two groups: no port site resection (No-PSR) and port site resection (PSR). Based on the pathological results of all port site specimens, PSR was classified as positive port site metastasis (PSM+) and negative port site metastasis (PSM-). RESULTS: In 82 cases, the laparoscopic port site access was resected in the debulking surgery. At the final specimen examination, 49% presented as PSM+. No statistical differences regarding survival were found, either between the No-PSR and PSR groups (p = 0.28) or between the PSM+ and PSM - groups (p = 0.92). A higher wound complication rate was found in the PSR group (17% vs. 34%; p = 0.047). The RR (Relative Risk) of wound events for PSR was 2.42 (95% CI 1.09-5.35; p = 0.0296). CONCLUSIONS: To date, not only there is no data supporting PSR after laparoscopy in advanced ovarian cancer, but the role of PSM+ in prognosis also remains unclear. In patients in which laparoscopy is performed prior to the debulking procedure, the PSR may not be recommended in those cases of no macroscopic port site metastasis.

[Seroprevalence and vertical transmission of Chagas disease in a cohort of Latin-american pregnant women in a tertiary hospital in Madrid]. / Seroprevalencia y transmisión vertical de enfermedad de Chagas en una cohorte de gestantes latinoamericanas en un hospital terciario de Madrid.

BACKGROUND: Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is endemic in Latin-America and is emerging in Spain due to immigration. The vertical transmission rate is around 5%. A routine prenatal screening with serology of all pregnant women from endemic areas is recommended to identify infected newborns, allowing early treatment and cure. OBJECTIVE: The aim of this study was to estimate the prevalence of positive Chagas serology in a cohort of pregnant women from Latin-America and its vertical transmission. PATIENTS AND METHODS: An observational, prospective, follow-up study was conducted on women with positive serology to T. cruzi, as well as their newborns, from January 2013 to April 2015. Congenital Chagas was ruled out using a PCR technique at birth and at 1 month, and with serology at 9-12 months old. A child was considered infected when PCR was positive, and uninfected when PCR was negative, and/or it had a negative serology. RESULTS: Screening was performed on 1244 pregnant women from Latin-America, and there were positive results in 40 (prevalence 3.2%, 95% CI: 2.4-4.4%), with 85% of them from Bolivia. There was only one infected newborn (rate of vertical transmission 2.8% (95% CI: 0-15%)), who had a positive PCR at birth. Relative studies enabled an 8-year-old sister with an asymptomatic disease to be diagnosed and treated. Both were treated successfully with benznidazole (later the PCR and serology were negative). CONCLUSION: Screening during pregnancy in Latin-American women helped to detect those with Chagas disease. The rate of vertical transmission was 2.8%, in keeping with literature. Screening led to the detection and treatment of previously unidentified familial cases.

Comparison of Mycobacterium lentiflavum and Mycobacterium avium-intracellulare complex lymphadenitis.

BACKGROUND: Mycobacterium lentiflavum is considered a rare pathogen causing nontuberculous mycobacterial (NTM) lymphadenitis. METHODS: A multicenter, retrospective study was performed in immunocompetent children <14 years of age with microbiologically confirmed NTM lymphadenitis treated at 6 hospitals in Madrid, Spain, during 2000-2010. We compared children with M. lentiflavum and Mycobacterium avium-intracellulare complex infection. RESULTS: Forty-five microbiologically confirmed NTM lymphadenitis patients were identified: 19 (45.2%) caused by M. avium-intracellulare complex, 17 (40.5%) by M. lentiflavum, 1 by both and 5 by other mycobacteria. Out of 17 M. lentiflavum cases, 14 were diagnosed in the past 5 years. Regarding M. lentiflavum cases, median age was 23 months. Submandibular nodes were the most frequently involved (76.5%), with multiple locations seen in 41% of the children and spontaneous drainage in 41% of them. Drug susceptibility tests were performed in 14 isolates and showed a complete susceptibility to clarithromycin and cycloserine, whereas 93% were resistant to rifampin, 33% to quinolones and full resistance to other tested antimycobacterial drugs was detected. All but 1 child required surgery and 11 were treated additionally with various drug combinations. Total resolution was achieved in 50% of children within 6 months.Compared with M. avium-intracellulare complex cases, children were younger and laterocervical nodes were significantly less frequently involved. No statistically significant differences were found related to clinical characteristics, treatment and outcome. CONCLUSIONS: M. lentiflavum is an emerging pathogen producing NTM lymphadenitis in Madrid.

Once-daily antiretroviral therapy in a cohort of HIV-infected children and adolescents.

We evaluated the evolution over time of once-daily antiretroviral therapy in HIV-infected children and its relationship with adherence. An increase on the prevalence of once-daily antiretroviral therapy was observed over time (from 0.9% in 2002 to 44.2% in 2011). There was no difference in adherence regarding once-daily or BID regimens in 2011. Adherence was related to age and pill burden.

Apendicolitiasis: revisión y serie clínica / Appendicolithiasis: Review and case series report

La presencia de cálculos (coprolitos, fecalitos o apendicolitos) en el lumen del apéndice cecal se denomina apendicolitiasis. Es un hallazgo frecuente, especialmente en niños, sometidos a apendicectomía por apendicitis aguda. También puede ser un hallazgo imagenológico en el estudio de un paciente por otro motivo. Históricamente se ha postulado la relación causal con apendicitis, pero la literatura reciente postula que el factor obstructivo adjudicado al apendicolito pareciera asociarse solo a la presencia de complicaciones y no ser un elemento causal de apendicitis aguda. Hasta el momento, no existe evidencia suficiente para plantear un manejo estandarizado ante el hallazgo de apendicolitiasis en pacientes asintomáticos. Presentamos cuatro casos clínicos de pacientes con apendicolitiasis, todos los cuales consultaron por dolor abdominal, descartándose cuadro agudo y fueron sometidos a cirugía diferida. El examen histopatológico de nuestros pacientes demostró en todos, algún grado de inflamación apendicular, reafirmando la necesidad de someter a cirugía los pacientes con apendicolitiasis sintomática. Se realiza una revisión bibliográfica del tema y las diferentes opciones ante al hallazgo de un coprolito apendicular.

The presence of calculi (coproliths, fecaliths or appendicoliths) in the appendiceal lumen is refered to as appendicolithiasis. It is a common finding, especially in pediatric patients undergoing surgery for acute appendicitis. Appendicolithiasis can also be a finding in patients undergoing diagnostic imaging tests for other conditions. Historically a casual relation has been considered between appendicolithiasis and appendicitis, but recent literature shows that the presence of an appendicolith is associated with complications but it is not the cause of appendicitis. So far, there is not enough evidence supporting a standarized treatment for patients with asymptomatic appendicolithiasis. We present four clinical cases and a review of relevant literature.

An intervention integrated into daily clinical practice reduces the incidence of delirium during hospitalization in elderly patients.

OBJECTIVES: To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients. DESIGN: Controlled study comparing an intervention in a geriatric unit (GI) with usual care in two internal medicine services (UC). SETTING: University hospital in Madrid, Spain. PARTICIPANTS: Five hundred forty-two consecutive patients (170 GI, 372 UC), aged 70 and older, with any of the risk criteria for delirium (cognitive impairment, visual impairment, acute disease severity, dehydration). INTERVENTION: Educational measures and specific actions in seven risk areas (orientation, sensory impairment, sleep, mobilization, hydration, nutrition, drug use). Daily monitoring of adherence. MEASUREMENTS: Baseline characteristics, risk factors for delirium, and quality care indicators were analyzed. The primary endpoint was incidence of delirium assessed daily. The secondary endpoint was functional decline, defined as loss of independence in any of the activities of daily living. The intervention effect was evaluated using logistic regression analysis. RESULTS: Delirium affected 11.7% of the GI group and 18.5% of the UC group (P=.04). After adjustment for confounders, the intervention was associated with lower incidence of delirium (odds ratio=0.4, 95% confidence interval=0.24-0.77; P=.005). In the patients who experienced delirium, severity, length, and recurrence of episodes were similar in both groups. Adherence to the intervention protocols was 75.7%. The intervention reduced the rate of functional decline (45.5% in GI vs 56.3% in UC, P=.03) and improved other quality indicators (e.g., mobilization and physical restraints reduction). CONCLUSION: A multicomponent, nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients, improves quality of care, and can be implemented without additional resources in a public healthcare system.