Conciliação medicamentosa na admissão de pacientes transplantados renais em um hospital universitário / Medication reconciliation in the admission of kidney transplant patients to a university hospital

Introdução:O presente estudo considerou conciliações medicamentosas realizadas na admissão hospitalar de pacientes transplantados renais e intervenções farmacêuticas decorrentes desse processo.Métodos:Trata-se de um estudo transversal realizado no período de julho de 2018 a julho de 2019 no Hospital de Clínicas de Porto Alegre. Foram coletadas as características dos pacientes, as conciliações medicamentosas realizadas pelo farmacêutico clínico, as discrepâncias identificadas pelo mesmo (intencionais e não intencionais) e o resultado das intervenções. Os medicamentos foram classificados de acordo com a Anatomic Therapeutic Chemical (ATC).Resultados:Dos 719 pacientes acompanhados pelo farmacêutico clínico, 175 tiveram a conciliação medicamentosa de admissão realizada, desses, 56 apresentaram discrepâncias não intencionais. Encontramos a média de 2,2 medicamentos omissos por prescrição com desvio padrão de 1,3 medicamentos. No total, foram realizadas 122 intervenções farmacêuticas, sendo que em 61,5% houve adesão por parte da equipe médica. A classe terapêutica com maior ocorrência (43,4%) de discrepâncias não intencionais foi a que atuava sobre o aparelho cardiovascular. As variáveis observadas foram sexo, número de medicamentos nas intervenções (ambas com associação significativa com a adesão médica), idade, tempo de internação, número de medicamentos na internação e número de medicamentos de uso prévio (estas últimas sem associação significativa com a adesão médica). Conclusões:A conciliação medicamentosa previne possíveis erros de medicação, uma vez que a identificação das discrepâncias não intencionais na prescrição médica gera sinalizações que são levadas pelo farmacêutico clínico à equipe assistente, a fim garantir o uso seguro e correto dos medicamentos durante a internação hospitalar.

Introduction:This study considered medication reconciliations performed on hospital admission of kidney transplant patients and pharmaceutical interventions resulting from this process.Methods:This is a cross-sectional study carried out from July 2018 to July 2019 at Hospital de Clínicas de Porto Alegre. The characteristics of the patients, the medication reconciliations performed by the clinical pharmacist, the discrepancies identified by the same (intentional and unintentional) and the result of the interventions were collected. The drugs were classified according to the Anatomic Therapeutic Chemical (ATC). Results:Of the 719 patients monitored by the clinical pharmacist, 175 had medication reconciliation on admission performed, of which 56 had unintentional discrepancies. We found an average of 2.2 missing medications per prescription with a standard deviation of 1.3 medications. In total, 122 pharmaceutical interventions were performed, and in 61.5% there was adherence by the medical team. The therapeutic class with the highest occurrence (43.4%) of unintentional discrepancies was that which acted on the cardiovascular system. The variables observed were gender, number of medications in interventions (both with a significant association with medical adherence), age, length of stay, number of medications in hospitalization and number of medications previously used (the latter without a significant association with medical adherence).Conclusions:Medication reconciliation prevents possible medication errors, since the identification of unintentional discrepancies in the medical prescription generates signals that are taken by the clinical pharmacist to the assistant team, in order to guarantee the safe and correct use of medications during hospitalization.

High farnesoid X receptor expression predicts favorable clinical outcomes in PD­L1low/negative non­small cell lung cancer patients receiving anti­PD­1­based chemo­immunotherapy.

Anti­programmed death­1 (PD­1)/programmed death­ligand 1 (PD­L1)­directed immunotherapy has revolutionized the treatment of advanced non­small cell lung cancer (NSCLC). However, predictive biomarkers are still lacking, particularly in identifying PD­L1low/negative patients who will benefit from immunotherapy. It was previously reported that farnesoid X receptor (FXR) downregulated PD­L1 expression in NSCLC, and that FXRhighPD­L1low mouse Lewis lung carcinoma tumors showed an increased susceptibility to PD­1 blockade compared with mock tumors. At present, whether the FXRhighPD­L1low phenotype predicts clinical response to immunotherapy in patients with NSCLC remains unclear. Herein, a retrospective study was conducted to examine the expression levels of FXR, PD­L1 and CD8+ T cells by immunohistochemistry in a cohort of 149 patients with NSCLC receiving anti­PD­1­based chemo­immunotherapy. The results revealed that high FXR and PD­L1 expression levels were associated with higher objective response rates (ORR) in all patients. High PD­L1 expression also indicated superior progression­free survival (PFS). Interestingly, an inverse correlation was identified between FXR and PD­L1 expression in specimens with NSCLC. Subgroup analysis revealed that high FXR expression was associated with a higher ORR, as well as longer PFS and overall survival (OS) in PD­L1low patients. Cox multivariate analysis revealed that high FXR expression was an independent predictor for PFS and OS in PD­L1low patients. Tumor microenvironment evaluation revealed a statistically significant decrease of infiltrating CD8+ T cells in FXRhigh specimens with NSCLC. Overall, the present study proposed an FXRhighPD­L1low signature as a candidate predictor of response to anti­PD­1­based chemo­immunotherapy in PD­L1low/negative patients with NSCLC, providing evidence that could be used to broaden the patients benefitting from immunotherapy.

Editorial on the Special Issue "Botulinum Toxin for the Treatment of Neurological Disorders: Where We Are and Where We Need to Go".

Over the past 30 years, botulinum toxin (BoNT) has seen an ever-expanding use in disorders afflicting the nervous system [...].

Pharmacological treatment after acute coronary syndrome: Baseline clinical characteristics and gender differences in a population-based cohort study / Tratamiento farmacológico después de un síndrome coronario agudo: características clínicas y diferencias de género en un estudio poblacional de cohortes

Objective: To describe baseline socio-demographic and clinical characteristics and drugs prescribed for secondary prevention after a first episode of ACS and to assess differences between men and women.SettingPHC in Catalonia. Data source: SIDIAP (Information System for Research in Primary Care).ParticipantsPatients who suffered an ACS during 2009–2016 and followed-up in PHC centres of the Catalan Health Institute in Catalonia.InterventionsNot applicable.Main measuresSocio-demographic and clinical characteristics at baseline: sex, age, socioeconomic index, toxic habits, comorbidities, study drugs (prescribed for cardiovascular secondary prevention: antiplatelets, betablockers, statins, drugs acting on the renin–angiotensin system) and comedications.Results8071 patients included, 71.3% of them were men and 80.2% had an acute myocardial infarction. Their mean age was 65.3 and women were older than men. The most frequent comorbidities were hypertension, dyslipidaemia and diabetes and they were more common in women. Antiplatelets (91.3%) and statins (85.7%) were the study drugs most prescribed. The uses of all comedications were significantly higher in women, except for nitrates. The combination of four study groups was initially prescribed in 47.7% of patients and combination of beta-blockers, statins and antiplatelets was prescribed in 18.4%. More men than women received all recommended pharmacological groups.ConclusionWomen were older, had more comorbidities and received more comedications. Most patients were treated with a combination of four or three study drugs for secondary prevention. Men initiated more drug treatments for secondary prevention and dual antiplatelet therapy than women.

Objetivos: Describir las características sociodemográficas y clínicas basales, y los fármacos prescritos para la prevención cardiovascular secundaria tras un síndrome coronario agudo (SCA). Analizar si existen diferencias entre varones y mujeres.EmplazamientoAtención primaria (AP) en Cataluña. Fuente de datos: Sistema de Información para el Desarrollo de la Investigación en AP (SIDIAP).ParticipantesPacientes que hayan sufrido un primer SCA durante 2009-2016, seguidos en AP del Instituto Catalán de la Salud en Cataluña.IntervencionesNo aplica.Mediciones principalesCaracterísticas sociodemográficas y clínicas al inicio: sexo, edad, índice socioeconómico, hábitos tóxicos, comorbilidades, fármacos de estudio (prescritos para prevención secundaria: antiagregantes, betabloqueantes, estatinas, fármacos del sistema renina-angiotensina) y fármacos concomitantes.ResultadosSe incluyeron 8.071 pacientes; 71,3% varones y 80,2% habían sufrido infarto. La edad media era de 65,3 años y las mujeres eran mayores que los varones. Las comorbilidades más frecuentes fueron hipertensión, dislipemia y diabetes; más comunes en mujeres. Antiagregantes (91,3%) y estatinas (85,7%) fueron los fármacos más prescritos. El uso de todas las comedicaciones era más frecuente en mujeres, excepto nitratos. La combinación de los 4 grupos farmacológicos de estudio se prescribió al 47,7% de los pacientes incluidos y la combinación de antiagregante, betabloqueante y estatina al 18,4%. Más varones que mujeres recibieron los fármacos recomendados.ConclusionesLas mujeres incluidas eran mayores, con más comorbilidad y mayor uso de comedicaciones. La mayoría de pacientes eran tratados con la combinación de 3 o 4 fármacos para prevención secundaria. Los varones iniciaban más fármacos para prevención secundaria y más terapia antiagregante doble que las mujeres.

Anterior gradient protein 2 is a marker of tumor aggressiveness in breast cancer and favors chemotherapy­induced senescence escape.

Among the different chemotherapies available, genotoxic drugs are widely used. In response to these drugs, particularly doxorubicin, tumor cells can enter into senescence. Chemotherapy­induced senescence (CIS) is a complex response. Long described as a definitive arrest of cell proliferation, the present authors and various groups have shown that this state may not be complete and could allow certain cells to reproliferate. The mechanism could be due to the activation of new signaling pathways. In the laboratory, the proteins involved in these pathways and triggering cell proliferation were studied. The present study determined a new role for anterior gradient protein 2 (AGR2) in vivo in patients and in vitro in a senescence escape model. AGR2's implication in breast cancer patients and proliferation of senescent cells was assessed based on a SWATH­MS proteomic study of patients' samples and RNA interference technology on cell lines. First, AGR2 was identified and it was found that its concentration is higher in the serum of patients with breast cancer and that this high concentration is associated with metastasis occurrence. An inverse correlation between intratumoral AGR2 expression and the senescence marker p16 was also observed. This observation led to the study of the role of AGR2 in the CIS escape model. In this model, it was found that AGR2 is overexpressed in cells during senescence escape and that its loss considerably reduces this phenomenon. Furthermore, it was shown that the extracellular form of AGR2 stimulated the reproliferation of senescent cells. The power of proteomic analysis based on the SWATH­MS approach allowed the present study to highlight the mammalian target of rapamycin (mTOR)/AKT signaling pathway in the senescence escape mechanism mediated by AGR2. Analysis of the two signaling pathways revealed that AGR2 modulated RICTOR and AKT phosphorylation. All these results showed that AGR2 expression in sera and tumors of breast cancer patients is a marker of tumor progression and metastasis occurrence. They also showed that its overexpression regulates CIS escape via activation of the mTOR/AKT signaling pathway.

Effects of COVID-19 pandemic on head and neck oncology activity: the experience of our University Hospital.

OBJECTIVE: The COVID-19 pandemic has severely affected otolaryngology and head and neck activities, also involving diagnosis and treatment of patients with oncology diseases with consequent delays and tumor upstaging. The aim of this study was to describe the experience of our otolaryngology unit during the pandemic on patients with cancer of the head and neck, comparing data on anatomical site of origin and preferred treatment with pre-pandemic data. PATIENTS AND METHODS: This study retrospectively analyzed the clinical records of patients treated for oncology disorders of the head and neck in the Otolaryngology Unit of the Policlinico Umberto I, Sapienza University of Rome, between March 10, 2020, and March 9, 2021. Data were compared with the same period of the previous year (March 10, 2019 - March 9, 2020). RESULTS: During the pandemic, we treated 92 patients with malignant tumor of the head and neck, compared to 101 patients treated during the same period of 2019 (-8.91%). The most common anatomical sites of origin of the neoplasms were larynx, oral cavity, and oropharynx. Surgical approach was preferred in 57 patients (61.95%); non-surgical treatments were performed in 35 cases (38.05%). Compared to the same period of the previous year, we found a 12.90% decrease in the number of oncology patients undergoing surgery, while patients treated exclusively with non-surgical approaches increased by 18.42%. CONCLUSIONS: Despite the impact of COVID-19 on the activity of our otolaryngology unit and on the whole healthcare system, diagnostic and therapeutic procedures for patients affected by malignancy of head and neck region were only minimally impacted.

Medical Outcomes, Quality of Life, and Family Perceptions for Outpatient vs Inpatient Neutropenia Management After Chemotherapy for Pediatric Acute Myeloid Leukemia.

Importance: Pediatric acute myeloid leukemia (AML) requires multiple courses of intensive chemotherapy that result in neutropenia, with significant risk for infectious complications. Supportive care guidelines recommend hospitalization until neutrophil recovery. However, there are little data to support inpatient over outpatient management. Objective: To evaluate outpatient vs inpatient neutropenia management for pediatric AML. Design, Setting, and Participants: This cohort study used qualitative and quantitative methods to compare medical outcomes, patient health-related quality of life (HRQOL), and patient and family perceptions between outpatient and inpatient neutropenia management. The study included patients from 17 US pediatric hospitals with frontline chemotherapy start dates ranging from January 2011 to July 2019, although the specific date ranges differed for the individual analyses by design and relative timing. Data were analyzed from August 2019 to February 2020. Exposures: Discharge to outpatient vs inpatient neutropenia management. Main Outcomes and Measures: The primary outcomes of interest were course-specific bacteremia incidence, times to next course, and patient HRQOL. Course-specific mortality was a secondary medical outcome. Results: Primary quantitative analyses included 554 patients (272 [49.1%] girls and 282 [50.9%] boys; mean [SD] age, 8.2 [6.1] years). Bacteremia incidence was not significantly different during outpatient vs inpatient management (67 courses [23.8%] vs 265 courses [29.0%]; adjusted rate ratio, 0.73; 95% CI, 0.56 to 1.06; P = .08). Outpatient management was not associated with delays to the next course compared with inpatient management (mean [SD] 30.7 [12.2] days vs 32.8 [9.7] days; adjusted mean difference, -2.2; 95% CI, -4.1 to -0.2, P = .03). Mortality during intensification II was higher for patients who received outpatient management compared with those who received inpatient management (3 patients [5.4%] vs 1 patient [0.5%]; P = .03), but comparable with inpatient management at other courses (eg, 0 patients vs 5 patients [1.3%] during induction I; P = .59). Among 97 patients evaluated for HRQOL, outcomes did not differ between outpatient and inpatient management (mean [SD] Pediatric Quality of Life Inventory total score, 70.1 [18.9] vs 68.7 [19.4]; adjusted mean difference, -2.8; 95% CI, -11.2 to 5.6). A total of 86 respondents (20 [23.3%] in outpatient management, 66 [76.7%] in inpatient management) completed qualitative interviews. Independent of management strategy received, 74 respondents (86.0%) expressed satisfaction with their experience. Concerns for hospital-associated infections among caregivers (6 of 7 caregiver respondents [85.7%] who were dissatisfied with inpatient management) and family separation (2 of 2 patient respondents [100%] who were dissatisfied with inpatient management) drove dissatisfaction with inpatient management. Stress of caring for a neutropenic child at home (3 of 3 respondents [100%] who were dissatisfied with outpatient management) drove dissatisfaction with outpatient management. Conclusions and Relevance: This cohort study found that outpatient neutropenia management was not associated with higher bacteremia incidence, treatment delays, or worse HRQOL compared with inpatient neutropenia management among pediatric patients with AML. While outpatient management may be safe for many patients, course-specific mortality differences suggest that outpatient management in intensification II should be approached with caution. Patient and family experiences varied, suggesting that outpatient management may be preferred by some but may not be feasible for all families. Further studies to refine and standardize safe outpatient management practices are warranted.

Estudio de utilización de psicofármacos en usuarios de la policlínica del Hospital Vilardebó con diagnóstico de esquizofrenia (años 2006 y 2016) / Study of the use of psychotropic drugs in users of the Vilardebó Hospital polyclinic with a diagnosis of schizophrenia (2006 and 2016)

El tratamiento farmacológico de demostrada eficacia en la esquizofrenia es el antipsicótico. Sin embargo, en muchas ocasiones se requiere medicación concomitante que depende de comorbilidades y efectos adversos. Se realizó un estudio cuantitativo, longitudinal, retrospectivo, considerando el año 2006 y 2016, en una población de usuarios con esquizofrenia de la Policlínica del Hospital Vilardebó, analizando los tratamientos con psicofármacos. Se diferenciaron los tratamientos según monoterapia antipsicótica y polifarmacia con 2 antipsicóticos, y polifarmacia con más de 2 antipsicóticos, antidepresivos, estabilizantes del humor, benzodiacepinas y anticolinérgicos. La población inicial en 2006 fue de 621 pacientes y 398 pacientes continuaban en tratamiento en 2016. Mantuvieron el trata-miento con antipsicóticos 377 pacientes; 184 mantuvieron benzodiacepinas; 59 se mantuvieron con anticolinérgicos; 49, con estabilizantes del humor y 47, con antidepresivos. La monoterapia antipsicótica se presentó en torno al 50 % de la población estudiada. Se deberían revisar aquellas prácticas que se infieren a partir de este estudio, como el uso prolongado de anticolinérgicos, benzodiacepinas, y polifarmacia con más de 2 antipsicóticos, que está extendida en los usuarios con esquizofrenia. El tratamiento con clozapina fue el más estable y no parece aumentar la mortalidad en estos pacientes

Antipsychotics are the proved effective therapy for schizophrenia. However, on many occasions, associated drugs are required depending on comorbidities and side effects. A retrospective longitudinal quantitative study of drug prescription for 2006 and 2016 in patients with schizophrenia diagnosis was carried out in an outpatient clinic at Hospital Vilardebó. Treatments were classified as antipsychotic monotherapy, two antipsychotic drugs polypharmacy and polypharmacy with two antipsychotic drugs, antidepressants, mood stabilizers, benzodiazepines and anticholinergic drugs. Initial population in 2006 included 621 patients, 398 were still being treated in 2016. Antipsychotic drugs were still being received in 377 patients, benzodiazepines in 184, anticholinergic drugs in 59, mood stabilizers in 49, and anti-depressants in 47. Antipsychotic monotherapy was 50% of the population. Those practices that can be inferred from this study, with lengthy use of anticholinergic drugs, benzodiazepines, and the use of more than 2 antipsychotic drugs in patients with schizophrenia diagnosis should be revised. Clozapine therapy was the most stable and does not seem to increase mortality.

Impact of COVID-19 Pandemic on Surgical Breast Cancer Patients Undergoing Neoadjuvant Therapy: A Multicentric Study.

BACKGROUND/AIM: Due to the SARS-CoV-2 pandemic, many scientific committees proposed neoadjuvant therapy (NACT) bridging treatment as a novel strategy and indication. The aim of the study was to evaluate the impact of COVID-19 pandemic on breast cancer patients undergoing NACT. PATIENTS AND METHODS: All breast cancer patients referred to two Breast Units during COVID-19-pandemic were enrolled. RESULTS: Out of 814 patients, 43(5.3%) were enrolled in the COVID-19-group and compared with 94 (7.9%) similar Pre-COVID-19 patients. We observed a reduction in the number of patients undergoing NACT, p=0.0019. No difference was reported in terms of clinical presentation, indications, and tumor response. In contrast, a higher number of vascular adverse events was reported (6.9% vs. 0% p=0.029). Immediate breast cancer reconstructions following invasive surgery suffered a significant slowdown (5.9% vs. 47.7%, p=0.019). CONCLUSION: COVID-19 caused a reduction in the number of patients undergoing NACT, with no changes in terms of indications, clinical presentation, and tumor response. Furthermore, there was an increased incidence of vascular events.

Combined radiotherapy and chemotherapy versus radiotherapy alone in elderly patients with nasopharyngeal carcinoma: A SEER population-based study.

ABSTRACT: Currently, the impact of chemotherapy (CT) on survival outcomes in elderly patients with nasopharyngeal carcinoma (NPC) receiving radiation therapy (RT) remains controversial. This retrospective study aims to investigate survival outcomes in a cohort of elderly NPC patients receiving RT alone or together with CT.Clinical data on 529 NPC patients aged 65 years and older extracted from the Surveillance, Epidemiology, and End Results registry (2004-2015) was collected and retrospectively reviewed. In this cohort, 74 patients were treated with RT alone and 455 individuals received RT and CT. We used propensity score matching with a 1:3 ratio to identify correlations between patients based on 6 different variables. Kaplan-Meier analysis was used to evaluate overall (OS) and cancer-specific survival (CSS). The differences in OS and CSS between the 2 treatment groups were compared using the Log-rank test and Cox proportional hazards models.The estimated 5-year OS and CSS rates for all patients were 49.5% and 59.3%, respectively. The combination of RT and CT provided longer OS than RT alone (53.7% vs 36.9%, P = .002), while no significant difference was observed in CSS (61.8% vs 51.7%, P = .074) between the 2 groups. Moreover, multivariate analysis demonstrated that the combination of CT and RT correlated favorably with OS and CSS. Subgroup analyses showed that the combination of RT and CT correlated better with both OS and CSS in patients with stage T3 or N2 or stage III.Among NPC patients aged 65 years and older, treatment with RT and CT provided longer OS than RT alone. Furthermore, the combination of RT and CT showed a better correlation with OS and CSS in NPC patients with stage T3 or N2 or stage III.

Variation in Management of Extremity Soft-Tissue Sarcoma in Younger vs Older Adults.

Importance: A large proportion of extremity soft-tissue sarcomas (ESS) occur among young adults, yet this group is underrepresented in clinical trials, resulting in limited data on this population. Younger patients present many complex challenges that affect clinical management. Objective: To investigate variations in treatment management in young adults vs older adults with ESS. Design, Setting, and Participants: This multicenter retrospective cohort study used the National Cancer Data Base (NCDB) to identify patients 18 years and older with ESS who received definitive treatment (ie, limb-sparing surgery [LSS] or amputation) between 2004 and 2014. Data analysis was conducted in November 2019. Exposures: Treatment regimen received among young adults (aged 18-39 years) and older adults (≥40 years) after diagnosis with ESS. Main Outcomes and Measures: To detect unique factors associated with treatment decisions in young adults with ESS, multivariable analyses used logistic regressions for patterns of treatment and their association with demographic factors and tumor characteristics. Results: Overall, 8953 patients were identified, and among these, 1280 (14.3%) were young adults. From the full cohort, 4796 patients (53.6%) identified as male and 6615 (73.9%) identified as non-Hispanic White. More young adults than older adults underwent amputation (age 18-39 years, 104 of 1280 [8.1%]; age 40-64 years, 217 of 3937 [5.5%]; aged ≥65 years, 199 of 3736 [5.3%]), but the association was not statistically significant (age ≥65 years, odds ratio [OR], 1.49; 95% CI, 1.00-2.23; P = .05). Young adults were more likely to receive chemotherapy than older patients (age 40-65 years, OR, 0.52; 95% CI, 0.45-0.60; P = .001; ≥65 years, OR, 0.16; 95% CI, 0.12-0.20; P = .001). Conversely, young adults were less likely to receive radiation therapy compared with older patients (age 40-65 years, OR, 1.40; 95% CI, 1.22-1.61; P = .001; ≥65 years, OR, 1.33; 95% CI, 1.10-1.61; P = .003). Unique to younger adults, clinical stage II disease vs stage I and positive surgical margins were not associated with use of radiation therapy (stage II disease: OR, 1.25; 95% CI, 0.81-1.91; P = .31; positive surgical margins: OR, 1.43; 95% CI, 0.93-2.22; P = .11). White Hispanic young adults were less likely than non-Hispanic White young adults to receive radiation therapy (OR, 0.53; 95% CI, 0.36-0.78; P = .002). Conclusions and Relevance: In this study, young adults with ESS were more likely to receive chemotherapy and less likely to receive radiation therapy than older adults. Further study is warranted to identify the clinical outcomes of these practice disparities.

Incidence of childhood hearing loss after in utero exposure to platinum agents.

OBJECTIVE: When treated for childhood cancers, at least 50% of children exposed to platinum agents have permanent hearing loss. We determined the relative risk of childhood hearing loss after in utero exposure to platinum chemotherapy in our registry cohort. METHOD: After exposure to platinum chemotherapy in utero, all children undergo routine newborn hearing screening. This consists of Otoacoustic Emissions. Children who failed this screen were evaluated by audiologists. For those children with hearing loss by Automated Auditory Brainstem Response, prenatal and postnatal treatment details were compared to platinum exposed children without hearing loss. RESULTS: Three hundred and seven children were exposed to chemotherapy in utero. Four children were diagnosed with hearing loss, all exposed to platinum agents. Chemotherapy exposures included: Cisplatin/Paclitaxel (2), Etoposide/Cisplatin/Bleomycin (1), Carboplatin/Paclitaxel (1) to treat ovarian (2), or cervical cancer (2). Of the 39 platinum exposed without hearing loss: 11 children were exposed to oxaliplatin, 16 were exposed to cisplatin and 12 to carboplatin in utero. Two hundred and sixty four women received non-platinum based chemotherapy for various cancers during pregnancy. Among these, there were no cases of hearing loss. There was a significant difference in hearing loss based on exposure to platinum agents in utero compared to non-platinum-containing chemotherapy regimens, 4/43 versus 0/264, p = 0.0003. There were no statistical differences in prenatal and postnatal treatment details, including: gestational age at diagnosis, at first chemotherapy treatment, at first platinum treatment, at delivery (<32 weeks, <35 weeks, <37 weeks), gender, birthweight, birthweight percentile, rates of intrauterine growth restriction, neonatal complications or use of postnatal antibiotics between the platinum exposed children with and without hearing loss. CONCLUSION: The only children in the registry exposed to chemotherapy who were diagnosed with hearing loss had been exposed to cisplatin or carboplatin in utero. No hearing loss occurred in children exposed to oxaliplatin, or non-platinum agents. Due to a concern for cisplatin ototoxicity, carboplatin is the preferred platinum agent for use in pregnancy when equivalent maternal survival can be expected for the particular cancer type. For newborns exposed to platinum agents in utero, newborn screening with an auditory emissions test at birth (OES) may not detect sensorineural hearing loss and auditory brainstem response testing is recommended, regardless of the newborn screening result.

Comparison of functional dorsal attention network alterations in breast cancer survivors before and after chemotherapy.

ABSTRACT: Breast cancer is the leading type of cancer among women worldwide, and a high number of breast cancer patients are suffering from psychological and cognitive disorders. This cross-sectional study used resting-state functional magnetic resonance imaging (rs-fMRI) and clinical neuropsychological tests to evaluate the possible underlying mechanisms.We enrolled 32 breast cancer patients without chemotherapy (BC), 32 breast cancer patients within 6 to 12 months after the completion of chemotherapy (BC_CTx) and 46 healthy controls. Participants underwent neuropsychological tests and rs-fMRI with mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity analyses. Between groups whole-brain voxel-wise rs-fMRI comparisons were calculated using two-sample t test. rs-fMRI and neuropsychological tests correlation analyses were calculated using multiple regression. Age and years of education were used as covariates. A false discovery rate-corrected P-value of less than .05 was considered statistically significant.We found significantly alteration of mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity in the frontoparietal lobe and occipital lobe in the BC group compared with the other 2 groups, indicating alteration of functional dorsal attention network (DAN). Furthermore, we found the DAN alteration was correlated with neuropsychological impairment.The majority of potential underlying mechanisms of DAN alteration in BC patients may due to insufficient frontoparietal lobe neural activity to drive DAN and may be related to the effects of neuropsychological distress. Further longitudinal studies with comprehensive images and neuropsychological tests correlations are recommended.

Associated factors with constipation and health-related quality of life in lung cancer patients with platinum-based chemotherapy: A cross-sectional study.

ABSTRACT: The main purpose of this study was to investigate current state of constipation for lung cancer (LC) patients receiving platinum-based chemotherapy. The relationships between social demography, clinical variables, psychological status, and constipation were analyzed. In addition, quality of life (QoL) in LC patients with constipation was also analyzed. One hundred LC patients participated in this cross-sectional study. Under the guidance of the researchers, Functional Living Index-Emesis, Piper Fatigue Scale, Patient Health Questionnaire, Generalized Anxiety Disorder-7, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0), Pittsburgh Sleep Quality Index, General Well-being Scale, Social Support Rate Scale, General Self-Efficacy Scale, and other related questionnaires were completed. The result showed the symptom of constipation was observed in 41 (41%) LC patients. The occurrence and development of constipation were associated with gender, food intake, exercise, nausea, fatigue, anxiety, depression, sleep disorders, and happiness. The study also found patients with constipation had significant lower QoL scores, especially the score in the general state. Constipation was very common in LC patients undergoing platinum-based chemotherapy. Reduced food intake and fatigue were the independent factors. Constipation significantly affects the QoL of the patients. Therefore, more attention should be paid to the risk factors of constipation in LC patients undergoing platinum-based chemotherapy, the earlier intervention was done to these patients, the better to improve their QoL.

Molecular Mechanism and Prevention Strategy of Chemotherapy- and Radiotherapy-Induced Ovarian Damage.

Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer.

Importance: Older adults are at greater risk of cognitive decline with various oncologic therapies. Some commonly used therapies for advanced prostate cancer, such as enzalutamide, have been linked to cognitive impairment, but published data are scarce, come from single-group studies, or focus on self-reported cognition. Objective: To longitudinally examine the association between cognitive function and docetaxel (chemotherapy), abiraterone, enzalutamide, and radium Ra 223 dichloride (radium 223) in older men with metastatic castration-resistant prostate cancer. Design, Setting, and Participants: A multicenter, prospective, observational cohort study was conducted across 4 academic cancer centers in Ontario, Canada. A consecutive sample of 155 men age 65 years or older with metastatic castration-resistant prostate cancer starting any treatment with docetaxel, abiraterone acetate, enzalutamide, or radium Ra 223 dichloride (radium 223) were enrolled between July 1, 2015, and December 31, 2019. Exposures: First-line chemotherapy (docetaxel), abiraterone, enzalutamide, or radium 223. Main Outcomes and Measures: Cognitive function was measured at baseline and end of treatment using the Montreal Cognitive Assessment, the Trail Making Test part A, and the Trail Making Test part B to assess global cognition, attention, and executive function, respectively. Absolute changes in scores over time were analyzed using univariate and multivariable linear regression, and the percentages of individuals with a decline of 1.5 SDs in each domain were calculated. Results: A total of 155 men starting treatment with docetaxel (n = 51) (mean [SD] age, 73.5 [6.2] years; 34 [66.7%] with some postsecondary education), abiraterone (n = 29) (mean [SD] age, 76.2 [7.2] years; 18 [62.1%] with some postsecondary education), enzalutamide (n = 54) (mean [SD] age, 75.7 [7.4] years; 33 [61.1%] with some postsecondary education), and radium 223 (n = 21) (mean [SD] age, 76.4 [7.2] years; 17 [81.0%] with some postsecondary education) were included. Most patients had stable cognition or slight improvements during treatment. A cognitive decline of 1.5 SDs or more was observed in 0% to 6.5% of patients on each measure of cognitive function (eg, 3 of 46 patients [6.5%; 95% CI, 2.2%-17.5%] in the group receiving chemotherapy [docetaxel] had a decline of 1.5 SDs for Trails A and Trails B). Although patients taking enzalutamide had numerically larger declines than those taking abiraterone, differences were small and clinically unimportant. Conclusions and Relevance: These findings suggest that most older men do not experience significant cognitive decline in attention, executive function, and global cognition while undergoing treatment for advanced prostate cancer regardless of the treatment used.

Bacterial superinfection in adults with COVID-19 hospitalized in two clinics in Medellín-Colombia, 2020.

COVID-19 represents high morbidity and mortality, its complications and lethality have increased due to bacterial superinfections. We aimed to determine the prevalence of bacterial superinfection in adults with COVID-19, hospitalized in two clinics in Medellín-Colombia during 2020, and its distribution according to sociodemographic and clinical conditions. A cross sectional study was made with 399 patients diagnosed with COVID-19 by RT-PCR. We determined the prevalence of bacterial superinfection and its factors associated with crude and adjusted prevalence ratios by a generalized linear model. The prevalence of superinfection was 49.6%, with 16 agents identified, the most frequent were Klebsiella (pneumoniae and oxytoca) and Staphylococcus aureus. In the multivariate adjustment, the variables with the strongest association with bacterial superinfection were lung disease, encephalopathy, mechanical ventilation, hospital stay, and steroid treatment. A high prevalence of bacterial superinfections, a high number of agents, and multiple associated factors were found. Among these stood out comorbidities, complications, days of hospitalization, mechanical ventilation, and steroid treatment. These results are vital to identifying priority clinical groups, improving the care of simultaneous infections with COVID-19 in people with the risk factors exposed in the population studied, and identifying bacteria of public health interest.

Abnormal methylation characteristics predict chemoresistance and poor prognosis in advanced high-grade serous ovarian cancer.

BACKGROUND: Primary or acquired chemoresistance is a key link in the high mortality rate of ovarian cancer. There is no reliable method to predict chemoresistance in ovarian cancer. We hypothesized that specific methylation characteristics could distinguish chemoresistant and chemosensitive ovarian cancer patients. METHODS: In this study, we used 450 K Infinium Methylation BeadChip to detect the different methylation CpGs between ovarian cancer patients. The differential methylation genes were analyzed by GO and KEGG Pathway bioinformatics analysis. The candidate CpGs were confirmed by pyrosequencing. The expression of abnormal methylation gene was identified by QRT-PCR and IHC. ROC analysis confirmed the ability to predict chemotherapy outcomes. Prognosis was evaluated using Kaplan-Meier. RESULTS: In advanced high-grade serous ovarian cancer, 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) remained hypermethylated in chemoresistant patients. The sensitivity, specificity and AUC of 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) methylation to predict chemotherapy sensitivity were 63.60-97.00%, 46.40-89.30% and 0.774-0.846. PFS of 6 candidate genes (ITGB6:cg21105318, cg07896068; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934) hypermethylation patients was significantly shorter. The expression of NCALD and LAMA3 in chemoresistant patients was lower than that of chemosensitive patients. Spearman analysis showed that NCALD and LAMA3 methylations were negatively correlated with their expression. CONCLUSIONS: As a new biomarker of chemotherapy sensitivity, hypermethylation of NCALD and LAMA3 is associated with poor PFS in advanced high-grade serous ovarian cancer. In the future, further research on NCALD and LAMA3 will be needed to provide guidance for clinical stratification of demethylation therapy.

Recognition and Management of Cutaneous Connective Tissue Diseases.

Connective tissue diseases (CTDs) encompass a broad spectrum of clinical presentations that involve multidisciplinary management. Cutaneous findings are common in CTD and careful examination of these features aids in appropriate diagnosis and subsequent evaluation. Thorough work-up of CTD is crucial to properly identify disease subtypes and systemic involvement. Management plans can be developed based on diagnosis and systemic manifestations of disease. Disease management often requires treatment with pharmacotherapies with potential for toxicities, further underscoring the importance of diagnostic accuracy in this patient population. Evolving research strives to better elucidate the pathogenic mechanisms of CTDs allowing for more targeted treatment modalities.