Enhanced recovery after surgery (ERAS®) society guidelines for gynecologic oncology: Addressing implementation challenges - 2023 update.

BACKGROUND: Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges. METHODS: Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018-2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly. CONCLUSIONS: The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.

Evidence of high compliance and fatigue in mask adherence in two mandates in Barcelona, Spain: a naturalistic observational study.

OBJECTIVE: We investigated a possible pandemic fatigue effect, comparing adherence to compulsory mask use outdoors in Barcelona during the fourth and sixth waves of the pandemic. STUDY DESIGN: We used naturalistic observation to determine the degree of pedestrians' compliance. METHODS: We assessed mask use outdoors in a sample of pedestrians in Barcelona between 28 December 2021 and 9 February 2022 (during the sixth wave in Spain), and compared it with the fourth wave (which was between 5 April 2021 and 29 April 2021). Masks were compulsory in both periods. RESULTS: The population studied amounted to 45,116 people (21,246 in the fourth wave and 23,870 in the sixth wave). In the sixth wave, only 67.3% wore a mask correctly, 18.6% did so incorrectly and 14.1% did not wear a mask, while the figures for the fourth wave were 78.2%, 16.3% and 5.5%, respectively (P = 0.001). CONCLUSION: Our results suggest that adherence was high in the population studied, but with an evident fatigue effect when the two waves were compared, as the proportion of individuals wearing a mask correctly declined compared to the fourth wave. These results suggest that policymakers need guidance on adopting clear and enforceable guidelines during future mask mandates, assessing advantages and drawbacks in terms of the population's behavior to prevent the fatigue effect.

[Telemedicine, ethics, and law in times of COVID-19. A look towards the future]. / Telemedicina, ética y derecho en tiempos de COVID-19. Una mirada hacia el futuro.

The health emergency in Spain caused by COVID-19 was of such a magnitude that on March 14, 2020, a state of alarm was declared that lasted for more than three months. This ongoing pandemic has affected a vast number of people. Among the measures taken to reduce the risk of contagion, visits to health centers have been reduced and virtual consultations have increased. Once the pandemic ends, it will be necessary to consider whether telemedicine should be limited to periods of health crises or whether it could become a new way of practicing medicine. Telemedicine lacks specific regulations and has loopholes that leave physicians with a considerable degree of insecurity. This article analyzes the limits, precautions, and legal standards of the use of telemedicine.

Measurements of adiposity as prognostic biomarkers for survival with anti-angiogenic treatment in epithelial ovarian cancer: An NRG Oncology/Gynecologic Oncology Group ancillary data analysis of GOG 218.

OBJECTIVE: Adiposity has been hypothesized to interfere with the activity of bevacizumab (BEV), an anti-angiogenic agent. Measurements of adiposity, BMI, surface fat area (SFA), and visceral fat area (VFA) were investigated as prognostic of oncologic outcomes among patients treated with chemotherapy, with or without BEV, on GOG 218, a prospective phase III trial. METHOD: Pretreatment computed tomography (CT) for 1538 GOG 218 participants were analyzed. Proportional hazards models assessed association between adiposity and overall survival (OS) adjusted for other prognostic factors. The predictive value of adiposity as a function of BEV treatment was assessed in 1019 patients randomized to either chemotherapy (CT) + placebo (P) → P or CT + BEV → BEV. RESULTS: After adjusting for prognostic factors, SFA was not associated with the overall hazard of death (p = 0.981). There was a non-significant 0.1% (p = 0.062) increase in hazard of death associated with a unit increase in VFA. When comparing the treatment HRs for patients who did and did not receive BEV, there was no association with SFA (p = 0.890) or VFA (p = 0.106). A non-significant 0.8% increase in the hazard of death with unit increase in BMI (p = 0.086) was observed. BMI values were not predictive of a longer survival for patients with BEV vs placebo (p = 0.606). CONCLUSION: Measures of adiposity strongly correlated to one another but were not predictive of efficacy for BEV. VFA is a weak prognostic factor.

Vaginal vs. robotic hysterectomy for patients with endometrial cancer: A comparison of outcomes and cost of care.

OBJECTIVE: To compare outcomes and cost for patients with endometrial cancer undergoing vaginal hysterectomy (VH) or robotic hysterectomy (RH), with or without lymphadenectomy (LND). METHODS: Patients undergoing planned VH (and laparoscopic LND) or RH (and robotic LND) between January 2007 and November 2012 were reviewed. Patients with stage IV disease, synchronous cancer, synchronous surgery, or treated with palliative intent were excluded. Patients were objectively triaged to LND per institutional protocol based on frozen section. Outcomes were compared between VH and RH groups matched 1:1 on propensity scores. RESULTS: VH was planned in 153 patients; 60 (39%) had concurrent LND while 93 (61%) were low risk and did not require LND. RH was planned in 398 patients; 225 (56%) required concurrent LND and 173 (44%) did not. Among 50 PS-matched pairs without LND, there was no significant difference in complications, length of stay, readmission, or progression free survival. However, median operative time was 1.3h longer and median 30-day cost $3150 higher for RH compared to VH (both p<0.001). Among patients requiring LND, 42 PS-matched pairs were identified. Median operative time was not different when pelvic and para-aortic LND was performed, and 12min longer in the VH group for pelvic LND alone (p=0.03). Median 30-day cost was $921 higher for RH compared to VH when LND was required (p=0.08). CONCLUSION: Utilization of vaginal hysterectomy for endometrial cancer results in similar surgical and oncologic outcomes and lower costs compared to RH and should be considered for appropriate patients with a low risk of requiring LND.

Virulence and genotypes of white spot syndrome virus infecting Pacific white shrimp Litopenaeus vannamei in north-western Mexico.

White spot syndrome virus (WSSV) has caused substantial global economic impact on aquaculture, and it has been determined that strains can vary in virulence. In this study, the effect of viral load was evaluated by infecting Litopenaeus vannamei with 10-fold serial dilution of tissue infected with strain WSSV Mx-H, and the virulence of four WSSV strains from north-western Mexico was assessed along with their variable number of tandem repeat (VNTR) genotypes in ORF75, ORF94 and ORF125. The LD50 of the Mx-H strain was a dilution dose of 10-7.5 ; the mortality titre was 109.2 LD50 per gram. In shrimp injected with 102.5 to 106.5 LD50 , no significant virulence differences were evident. Using mortality data, the four WSSV strains grouped into three virulence levels. The Mx-F strain (intermediate virulence) and the Mx-C strain (high virulence) showed more genetic differences than those observed between the Mx-G (low-virulence) and Mx-H (high-virulence) strains, in ORF94 and ORF125. The application of high-viral-load inocula proved useful in determining the different virulence phenotypes of the WSSV strains from the Eastern Pacific.

Lithium for treatment of amyotrophic lateral sclerosis: much ado about nothing. / Litio para el tratamiento de la esclerosis lateral amiotrófica: mucho ruido para nada.

INTRODUCTION: Lithium was proposed in 2008 as an effective candidate in the treatment of ALS after a report claimed that it was able to delay functional deterioration by 40% and that none of the 16 patients treated with a combination of lithium plus riluzole had died during a 15-month follow-up period. The excellent results of this pilot study engendered considerable optimism among patients, their families, patients' associations, and the scientific community. This report sparked numerous phase ii clinical trials. Many patients who were not included in these studies used all resources at their disposal to access the drug as treatment under a compassionate use programme. OBJECTIVES: To evaluate the effectiveness of lithium in ALS using a meta-analysis of the information reported in 12 studies which were examined for methodological quality. MATERIAL AND METHODS: . Searches were performed using MEDLINE, EMBASE, the Cochrane Neuromuscular Disease Group Trials Register, ClinicalTrials.gov, and EudraCT (January 1996-August 2012). RESULTS: To date, we have information on more 1100 patients treated with lithium. Unfortunately, the results do not confirm the positive effect described in the pilot study, which suggests that this drug is not effective at slowing disease progression. Two trials had to be suspended before the scheduled completion date due to the ineffectiveness of the drug as well as numerous adverse effects. A recently published study also ruled out any possible modest effect. CONCLUSIONS: There is evidence to suggest that lithium has no short-term benefits in ALS. A comparison of the group of patients treated with lithium+riluzole and the control group treated with riluzole alone showed no statistically significant differences in rates of functional decline, deterioration of respiratory function, or survival time. Furthermore, there was no evidence that it was more effective than the placebo.

[Comprehensive approach to vertigo: Diagnostic algorithm, causes, treatments, and referral criteria from the perspective of primary care. SEMERGEN consensus document]. / Abordaje integral del vértigo: algoritmo diagnóstico, causas, tratamientos y criterios de derivación desde la perspectiva de atención primaria. Documento de consenso SEMERGEN.

Vertigo is a common symptom that can have various causes and may require a comprehensive approach for its diagnosis and treatment from primary care. A diagnostic algorithm based on the classification proposed by the Otoneurology Commission of the SEORL-PCF is suggested, which facilitates the classification of the different types of vertigo and provides referral criteria for patients from primary care to other specialties. A review of the available treatments based on the underlying cause is conducted for appropriate therapeutic management. This document is expected to become a valuable tool for professionals treating patients with vertigo. The document is based on scientific evidence and on the experience of experts in the field from various medical specialties; and seeks to improve the understanding and clinical approach to acute vertigo from primary care.

SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.

Mutations in the SPG7 gene were initially reported in patients with autosomal recessive hereditary spastic paraplegia (HSP). Recent works suggested a dominant effect for some SPG7 mutations. To characterize the SPG7 mutational spectrum in a large cohort of Spanish HSP patients, we sequenced the whole SPG7 gene in a total of 285 Spastic Paraplegia patients. Large gene rearrangements were also ascertained in some patients. We found a total of 14 SPG7 mutations (12 new) in 14 patients; 2 were large deletions. All the mutation carriers had an adult onset age but only five (35%) had a complicated phenotype. We identified a single mutation in 13 patients. Familial analysis suggested a dominant inheritance for one (p.Leu78*) of these mutations. Carriers of the rare p.A510V variant were significantly more frequent in patients vs healthy controls (3% vs 1%), suggesting a pathogenic role for this SPG7 variant. We reported a high frequency of patients with only one SPG7 mutation, and a putative pathogenic role for the p.A510V variant.

Risk-scoring system for the individualized prediction of lymphatic dissemination in patients with endometrioid endometrial cancer.

OBJECTIVE: To develop a risk-scoring system (RSS) for the prediction of lymphatic dissemination after hysterectomy in endometrioid endometrial carcinoma (EC). METHODS: Patients who underwent surgery from 1/1/1999-12/31/2008 were evaluated. Patients with non-endometrioid histology, stage IV with macroscopic extrauterine disease, or receiving adjuvant therapy (excluding brachytherapy) without pelvic and/or paraaortic (P/PA) lymphadenectomy (LND) were excluded. Lymph node dissemination was defined as nodal metastasis when P/PA LND was performed or P/PA lymph node recurrence after negative LND or when LND was not performed. Logistic regression analysis was used to identify predictors for lymphatic dissemination and develop a RSS and nomogram. The RSS was assessed for calibration and verified for discrimination. RESULTS: Overall, 883 patients were assessed of which 521 (59.0%) underwent P/PA LND and 57 (10.9%) had positive lymph nodes. Of patients who did not undergo P/PA LND (N=362) or had negative nodes (N=464), 10 (1.2%) patients had P/PA lymph node recurrence. Myometrial invasion, tumor diameter (TD), FIGO grade, cervical stromal invasion and lymphovascular space invasion were significant on univariable analysis. All preceding variables were included in a multivariable logistic model. A parsimonious model and an alternative full model not including TD were considered. The full model with TD (illustrated in nomogram) had the highest predictive ability (concordance index 0.88). CONCLUSION: Our RSS allows accurate quantification of the probability of lymphatic dissemination and can be used as an adjunct to clinical decision-making after hysterectomy in the absence of staging. TD is an important component of the RSS and should be routinely assessed.

Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer.

OBJECTIVE: Preoperative thrombocytosis has been implicated as a negative prognostic marker for epithelial ovarian cancer (EOC). We assessed whether thrombocytosis is an independent risk factor for EOC recurrence and death. METHODS: Perioperative patient characteristics and process-of-care variables (National Surgical Quality Improvement Program (NSQIP)-defined) were retrospectively abstracted from 587 women who underwent EOC staging between 1/2/03-12/29/08. Thrombocytosis was defined as platelet count > 450 × 10(9)/L. Disease-free survival (DFS) and overall survival (OS) were determined using Kaplan-Meier methods. Associations were evaluated with Cox proportional hazards regression and hazard ratios (HR). RESULTS: The incidence of preoperative thrombocytosis was 22.3%. DFS was 70.8% and 36.0% at 1 and 3 years. OS was 83.3% and 54.3% at 1 and 3 years. Ascites, lower hemoglobin, advanced disease, and receipt of perioperative packed red blood cell transfusion were independently associated with thrombocytosis. Older age and the presence of coronary artery disease were associated with lower likelihood of thrombocytosis. Overall, thrombocytosis was an independent predictor of increased risk of recurrence. Among early stage (I/II) cases, there was a 5-fold increase in the risk of death and nearly 8-fold risk of disease recurrence independently associated with thrombocytosis. CONCLUSION: Preoperative thrombocytosis portends worse DFS in EOC. In early stage disease, thrombocytosis is a potent predictor of worse DFS and OS and further assessment of the impact of circulating platelet-derived factors on EOC survival is warranted. Thrombocytosis is also associated with extensive initial disease burden, measurable residual disease, and postoperative sequelae. Preoperative platelet levels may have value in primary cytoreduction counseling.

Risk factors that mitigate the role of paraaortic lymphadenectomy in uterine endometrioid cancer.

OBJECTIVE: Paraaortic lymph node (PA) dissemination in endometrial cancer (EC) is uncommon and a systematic infrarenal PA dissection carries morbidity. Our objective was to identify a subgroup of EC patients who may potentially forego PA lymphadenectomy (LND). METHODS: The study endpoint (PA Metastasis or Recurrence; PAMR) was defined as detection of metastasis to PA nodes (among those with any type of PA LND) or PA recurrence within 2 years (among patients without PA LND or those with negative nodes in the context of an inadequate (<5 nodes) PA LND). Patients with non-endometrioid histology, stage IV disease, synchronous cancers, gross extrauterine or gross adnexal disease, neoadjuvant therapy, or insufficient follow-up were excluded. Multivariable logistic regression analysis identified predictors of PAMR. RESULTS: Of the 946 patients, PAMR was observed in 4% (36/946). Multivariable analysis identified positive pelvic nodes (odds ratio (OR) 24.2; p<0.001), >50% MI (OR 5.3; p<0.001) and lymphovascular space invasion (LVSI) (OR 3.7; p=0.005) as the only three independent predictors of PAMR. When all three factors were absent (77% of study cohort), the predicted probability of PAMR was 0.6%. If intraoperative frozen section is not available on pelvic lymph nodes and LVSI, omitting PA LND in all patients with ≤ 50% MI would affect 84% (792/946) of the total cohort, with a 1.1% risk of PAMR (9/792). CONCLUSION: The majority of patients with endometrioid EC may potentially forgo PA LND with expected reductions in surgical morbidity and cost. This cohort may be identified by a combined absence of: positive pelvic nodes, >50% MI and LVSI.

Prospective assessment of survival, morbidity, and cost associated with lymphadenectomy in low-risk endometrial cancer.

OBJECTIVE: Since 1999, patients with low risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. Here we prospectively assess survival, sites of recurrence, morbidity, and cost in this low risk cohort. METHODS: Cause-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Complications were graded per the Accordion Classification. Thirty-day cost analyses were expressed in 2010 Medicare dollars. RESULTS: Among 1393 consecutive surgically managed cases, 385 (27.6%) met inclusion criteria, accounting for 34.1% of type I EC. There were 80 LND and 305 non-LND cases. Complications in the first 30 days were significantly more common in the LND cohort (37.5% vs. 19.3%; P<0.001). The prevalence of lymph node metastasis was 0.3% (1/385). Over a median follow-up of 5.4 years only 5 of 31 deaths were due to disease. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P=0.32). None of the 11 total recurrences occurred in the pelvic or para-aortic nodal areas. Median 30-day cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P<0.001). The estimated cost per up-staged low-risk case was $327,866 to $439,990, adding an additional $1,418,189 if all 305 non-LND cases had undergone LND. CONCLUSION: Lymphadenectomy dramatically increases morbidity and cost of care without discernible benefits in low-risk EC as defined by the Mayo criteria. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care.

Incidence and factors associated with synchronous ovarian and endometrial cancer: a population-based case-control study.

OBJECTIVE: To estimate the incidence of synchronous endometrial cancer (EC) and ovarian cancer (OC) in the female population, among all women with EC, and in women under 50 years of age with EC, and to identify factors associated with synchronous EC/OC. METHODS: All cases of synchronous EC/OC and EC diagnosed in women residing in Olmsted County, Minnesota between 1/1/1945 and 12/31/2008 were identified. Incidence was estimated using the population denominator from decennial census data, corrected for hysterectomy prevalence. A case-control study using 15 identified cases (EC/OC) and 45 controls (EC alone) was performed. RESULTS: The incidence of synchronous EC/OC and EC (age-adjusted to the 2000 US female total and corrected for hysterectomy prevalence) in 1945-2008 was 0.88 and 30.3 per 100,000 person-years, respectively. Among women under 50 years of age, the corrected incidence of EC/OC and EC was 0.51 and 5.1 per 100,000 person-years, respectively. Among all women with EC, 3.1% had a synchronous OC compared to 9.4% of women under 50 years of age with EC. Patients with synchronous EC/OC were more likely than those with EC alone to present with a pelvic mass (57.1% vs. 8.9%, p<0.001). Patients with EC alone were more likely to have used oral contraceptive pills (OCPs) than synchronous EC/OC cases (22.7% vs 0%; Odds ratio, 0.10; 95% CI, <0.01-0.87). CONCLUSION: Although the incidence of synchronous EC/OC in the general population is lower than previously reported, nearly 1 in 10 women diagnosed with EC under 50 years of age will have a synchronous OC.

The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor.

Homozygous mutations of the telomeric SMN1 gene lead to degeneration of motor neurons causing spinal muscular atrophy (SMA). A highly similar centromeric gene (SMN2) can only partially compensate for SMN1 deficiency. The c.859G>C variant in SMN2 has been recently reported as a positive disease modifier. We identified the variant in 10 unrelated chronic SMA patients with a wide spectrum of phenotypes ranging from type II patients who can only sit to adult walkers. Haplotype analysis strongly suggests that the variant originated from a common ancestor. Our results confirm that the c.859G>C variant is a milder SMN2 allele and predict a direct correlation between SMN activity and phenotypic severity.

Telemedicine, ethics, and law in times of COVID-19. A look towards the future.

The health emergency in Spain caused by COVID-19 was of such a magnitude that on March 14, 2020, a state of alarm was declared that lasted for more than three months. This ongoing pandemic has affected a vast number of people. Among the measures taken to reduce the risk of contagion, visits to health centers have been reduced and virtual consultations have increased. Once the pandemic ends, it will be necessary to consider whether telemedicine should be limited to periods of health crises or whether it could become a new way of practicing medicine. Telemedicine lacks specific regulations and has loopholes that leave physicians with a considerable degree of insecurity. This article analyzes the limits, precautions, and legal standards of the use of telemedicine.

[Filnut-scale: rationale and use in screening for malnutrition risk within the infornut process]. / Filnut-escala: justificación y utilidad en el cribaje de riesgo por desnutrición dentro del proceso infornut.

OBJECTIVES: To offer a rationale for assigning a minimum score for risk of malnutrition for total proteins lower than 5g/dl and a scoring scale for our filter (FILNUT-Scale); and to analyse results of the MUST screening test performed on positive scores in the FILNUT nutritional filter and assess usefulness of said test in this population. METHODS: We searched the laboratory database for laboratory test orders (dated between 2004 and 2007) for which total proteins and albumin or cholesterol levels were determined, and we identified those with results for the above three parameters plus lymphocyte count. A limit (less than 5g/dl) was placed on the total protein level and the results for other parameters were not limited. Distribution curves for albumin and cholesterol were analysed. The same protocol was followed after establishing the CONUT score for each sample with the necessary parameters. From September 2007 to January 2008, the MUST test was performed on all FILNUT positives and we analysed how the degrees of risk corresponded. RESULTS: In 95% of the cases in which total proteins are lower than 5g/dl (n=1,176), albumin values are between 0.98 and 2.94g/dl, resulting in CONUT scores of 4 or 6 for albumin. Regarding total cholesterol, (n=761) 89.1% of the samples are lower than 180mg/dl, which accounts for one or two points in the score. In 98.79 % of the cases (n=490) that presented all four parameters, CONUT score was >/=5, which could be classified as medium or high risk. During the study period, 100% of the patients identified as medium or high risk by the FILNUT-Scale (n=568) tested as at-risk by MUST: of these, 421 (74.1%) were at high risk and 147 (25.9%) were at medium risk. CONCLUSIONS: Total proteins lower than 5g/dl determine a medium or high risk of malnutrition where a complete nutritional screening profile is lacking. This is why it should be included in the FILNUT-Scale with a score of five points. Performing the MUST test on patients with five or more points is efficient and provides clinical data needed for a complete assessment.