Objective
To assess the effect of transabdominal amnioinfusion or no intervention on long‐term outcomes in children born after second‐trimester prelabour rupture of the membranes (PROM between ...16+0/7–24+0/7 weeks) and oligohydramnios.
Population
Follow up of infants of women who participated in the randomised controlled trial: PPROMEXIL‐III (NTR3492).
Methods
Surviving infants were invited for neurodevelopmental assessment up to 5 years of corrected age using a Bayley Scales of Infant and Toddler Development or a Wechsler Preschool and Primary Scale of Intelligence. Parents were asked to complete several questionnaires.
Main outcome measures
Neurodevelopmental outcomes were measured. Mild delay was defined as −1 standard deviation (SD), severe delay as −2 SD. Healthy long‐term survival was defined as survival without neurodevelopmental delay or respiratory problems.
Results
In the amnioinfusion group, 18/28 children (64%) died versus 21/28 (75%) in the no intervention group (relative risk 0.86; 95% confidence interval CI 0.60–1.22). Follow‐up data were obtained from 14/17 (82%) children (10 amnioinfusion, 4 no intervention). In both groups, 2/28 (7.1%) had a mild neurodevelopmental delay. No severe delay was seen. Healthy long‐term survival occurred in 5/28 children (17.9%) after amnioinfusion versus 2/28 (7.1%) after no intervention (odds ratio 2.50; 95% CI 0.53–11.83). When analysing data for all assessed survivors, 10/14 (71.4%) survived without mild neurodevelopmental delay and 7/14 (50%) were classified healthy long‐term survivor.
Conclusions
In this small sample of women suffering second‐trimester PROM and oligohydramnios, amnioinfusion did not improve long‐term outcomes. Overall, 71% of survivors had no neurodevelopmental delay.
Tweetable
Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention.
Tweetable
Healthy long‐term survival was comparable for children born after second‐trimester PROM and treatment with amnioinfusion or no intervention.
Objectives
To evaluate variant histologies (VHs) for disease‐specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC).
Materials and ...Methods
We analysed a multi‐institutional cohort of 1082 patients treated with upfront RC for cT1‐4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox’ regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage‐based analyses. The stages were defined as ‘organ‐confined’ (≤pT2N0), ‘locally advanced’ (pT3‐4N0) and ‘node‐positive’ (pTanyN1‐3).
Results
Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients 3.7%), sarcomatoid (29 patients 2.7%), glandular (18 patients 1.7%), lymphoepithelioma‐like (14 patients 1.3%), small‐cell (13 patients 1.2%), clear‐cell (eight patients 0.7%), nested (seven patients 0.6%) and plasmacytoid VH (three patients 0.3%). The median follow‐up was 2.3 years. Overall, 534 (49.4%) disease‐related deaths occurred. In uni‐ and multivariable analyses, plasmacytoid and small‐cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma‐like VH had favourable DSS compared to pure UC. Clear‐cell (P = 0.015) and small‐cell (P = 0.011) VH were associated with worse DSS in the organ‐confined and node‐positive cohorts, respectively.
Conclusions
More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear‐cell, plasmacytoid, small‐cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma‐like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.
An imbalance in perioperative cytokine response may cause acute pain and postoperative complications. Anesthetic drugs modulate this cytokine response, but their role in non-major breast cancer ...surgery is unclear. In an exploratory study, we investigated whether intravenous lidocaine and dexamethasone could modulate the cytokine response into an anti-inflammatory direction. We also evaluated interrelationships between cytokine levels, pain scores and postoperative complications. Our goal is to develop multimodal analgesia regimens optimizing outcome after breast cancer surgery.
Forty-eight patients undergoing a lumpectomy were randomly assigned to placebo or lidocaine (1.5 mg⋅kg
followed by 2 mg⋅kg
⋅hour
) supplemented by dexamethasone zero, 4 or 8 mg, yielding six groups of eight patients. Interleukin (IL)-1β, IL-1Ra, IL-6, IL-10 levels and pain scores were measured at baseline and four hours postoperatively. We assessed postoperative complications occurring within 30 days. We noted persistent pain and infections as potential immune-related complications (PIRC). We used multiple regression to disentangle the effects of the individual study drugs (given by their partial regression coefficients (b)). Odds ratios (OR) estimated the link between pain scores and complications.
Dexamethasone 8 mg increased IL-10 (b=12.70 (95% CI=8.06-17.34),
<0.001). Dexamethasone 4 mg and 8 mg decreased the ratio IL-6/IL-10 (b=-2.60 (-3.93 to -1.26),
<0.001 and b=-3.59 (-5.04 to -2.13),
<0.001, respectively). We could not show modulatory effects of lidocaine on cytokines. High pain scores were linked to the occurrence of PIRC's (OR=2.028 (1.134-3.628),
=0.017). Cytokine levels were not related either to acute pain or PIRC.
Dexamethasone modulated the perioperative cytokine response into an anti-inflammatory direction. An overall lidocaine effect was not found. Patients with higher pain scores suffered from more 30-day PIRCs. Cytokine levels were not associated with pain or more postoperative complications, even not with PIRC. Larger studies in breast cancer surgery are needed to confirm these explorative results.
Objectives
To compare the prognostic value of the World Health Organization (WHO) 1973 and 2004 classification systems for grade in T1 bladder cancer (T1‐BC), as both are currently recommended in ...international guidelines.
Patients and Methods
Three uro‐pathologists re‐revised slides of 601 primary (first diagnosis) T1‐BCs, initially managed conservatively (bacille Calmette–Guérin) in four hospitals. Grade was defined according to WHO1973 (Grade 1–3) and WHO2004 (low‐grade LG and high‐grade HG). This resulted in a lack of Grade 1 tumours, 188 (31%) Grade 2, and 413 (69%) Grade 3 tumours. There were 47 LG (8%) vs 554 (92%) HG tumours. We determined the prognostic value for progression‐free survival (PFS) and cancer‐specific survival (CSS) in Cox‐regression models and corrected for age, sex, multiplicity, size and concomitant carcinoma in situ.
Results
At a median follow‐up of 5.9 years, 148 patients showed progression and 94 died from BC. The WHO1973 Grade 3 was negatively associated with PFS (hazard ratio HR 2.1) and CSS (HR 3.4), whilst WHO2004 grade was not prognostic. On multivariable analysis, WHO1973 grade was the only prognostic factor for progression (HR 2.0). Grade 3 tumours (HR 3.0), older age (HR 1.03) and tumour size >3 cm (HR 1.8) were all independently associated with worse CSS.
Conclusion
The WHO1973 classification system for grade has strong prognostic value in T1‐BC, compared to the WHO2004 system. Our present results suggest that WHO1973 grade cannot be replaced by the WHO2004 classification in non‐muscle‐invasive BC guidelines.
Background
Hypothalamic obesity (HO) is a major concern in patients treated for craniopharyngioma (CP). The influence of degree of resection on development of HO, event‐free survival (EFS), and ...neuroendocrine sequelae is an issue of debate.
Procedure
A retrospective cohort consisting of all CP patients treated between 2002 and 2012 in two university hospitals was identified. Multivariable logistic regression was used to study the associations between preoperative BMI, age at diagnosis, tumor volume, performed surgical resection, and presence of HO at follow‐up.
Results
Thirty‐five patients (21 children and 14 adults) were included. Median follow‐up time was 35.6 months (4.1–114.7). Four patients were obese at diagnosis. HO was present in 19 (54.3%) patients at last follow‐up of whom eight were morbidly obese. Thirteen (37.1%) patients underwent partial resection (PR) and 22 (62.9%) gross total resection (GTR). GTR was related to HO (OR 9.19, 95% CI 1.43–59.01), but for morbid HO, obesity at diagnosis was the only risk factor (OR 12.92, 95% CI 1.05–158.73). EFS in patients after GTR was 86%, compared to 42% after PR (log‐rank 9.2, P = 0.003). Adjuvant radiotherapy after PR improved EFS (log‐rank 8.2, P = 0.004). Panhypopituitarism, present in 15 patients, was mainly seen after GTR.
Conclusions
HO is less frequent after PR than after GTR, but PR cannot always prevent the development of morbid obesity in patients with obesity at diagnosis. PR reduces the occurrence of panhypopituitarism. When developing a treatment algorithm, all these factors should be considered.
In children, renal cell carcinoma (RCC) is rare. This study is the first report of pediatric patients with RCC registered by the International Society of Pediatric Oncology‐Renal Tumor Study Group ...(SIOP‐RTSG). Pediatric patients with histologically confirmed RCC, registered in SIOP 93‐01, 2001 and UK‐IMPORT databases, were included. Event‐free survival (EFS) and overall survival (OS) were analyzed using the Kaplan‐Meier method. Between 1993 and 2019, 122 pediatric patients with RCC were registered. Available detailed data (n = 111) revealed 56 localized, 30 regionally advanced, 25 metastatic and no bilateral cases. Histological classification according to World Health Organization 2004, including immunohistochemical and molecular testing for transcription factor E3 (TFE3) and/or EB (TFEB) translocation, was available for 65/122 patients. In this group, the most common histological subtypes were translocation type RCC (MiT‐RCC) (36/64, 56.3%), papillary type (19/64, 29.7%) and clear cell type (4/64, 6.3%). One histological subtype was not reported. In the remaining 57 patients, translocation testing could not be performed, or TFE‐cytogenetics and/or immunohistochemistry results were missing. In this group, the most common RCC histological subtypes were papillary type (21/47, 44.7%) and clear cell type (11/47, 23.4%). Ten histological subtypes were not reported. Estimated 5‐year (5y) EFS and 5y OS of the total group was 70.5% (95% CI = 61.7%‐80.6%) and 84.5% (95% CI = 77.5%‐92.2%), respectively. Estimated 5y OS for localized, regionally advanced, and metastatic disease was 96.8%, 92.3%, and 45.6%, respectively. In conclusion, the registered pediatric patients with RCC showed a reasonable outcome. Survival was substantially lower for patients with metastatic disease. This descriptive study stresses the importance of full, prospective registration including TFE‐testing.
What's new?
Pediatric renal cell carcinoma (RCC) is a rare malignancy, knowledge of which is based largely on adult RCC. Here, pediatric RCC was retrospectively studied using data from the International Society of Pediatric Oncology – Renal Tumor Study Group (SIOP‐RTSG). Pediatric RCC patients had a 5‐year overall survival rate of 84.5 percent, with notably lower survival for patients with metastatic disease. In pediatric RCC patients tested for transcription factor E3 and EB, 56.3 percent presented with translocation type. The findings highlight the importance of full registration of pediatric RCCs, with information on germline genetics and transcription factor testing.
RationaleThe positive end–expiratory pressure (PEEP) strategy in patients with coronavirus 2019 (COVID–19) acute respiratory distress syndrome (ARDS) remains debated. Most studies originate from the ...initial waves of the pandemic. Here we aimed to assess the impact of high PEEP/low FiO2 ventilation on outcomes during the second wave in the Netherlands.MethodsRetrospective observational study of invasively ventilated COVID–19 patients during the second wave. Patients were categorized based on whether they received high PEEP or low PEEP ventilation according to the ARDS Network tables. The primary outcome was ICU mortality, and secondary outcomes included hospital and 90–day mortality, duration of ventilation and length of stay, and the occurrence of kidney injury. Propensity matching was performed to correct for factors with a known relationship to ICU mortality.ResultsThis analysis included 790 COVID–ARDS patients. At ICU discharge, 32 (22.5%) out of 142 high PEEP patients and 254 (39.2%) out of 848 low PEEP patients had died (HR 0.66 0.46–0.96; P = 0.03). High PEEP was linked to improved secondary outcomes. Matched analysis did not change findings.ConclusionsHigh PEEP ventilation was associated with improved ICU survival in patients with COVID–ARDS.
Context. Cassiopeia A is one of the best-studied supernova remnants. Its bright radio and X-ray emission is due to shocked ejecta. Cas A is rather unique in that the unshocked ejecta can also be ...studied: through emission in the infrared, the radio-active decay of 44Ti, and the low-frequency free-free absorption caused by cold ionised gas, which is the topic of this paper. Aims. Free-free absorption processes are affected by the mass, geometry, temperature, and ionisation conditions in the absorbing gas. Observations at the lowest radio frequencies can constrain a combination of these properties. Methods. We used Low Frequency Array (LOFAR) Low Band Antenna observations at 30–77 MHz and Very Large Array (VLA) L-band observations at 1–2 GHz to fit for internal absorption as parametrised by the emission measure. We simultaneously fit multiple UV-matched images with a common resolution of 17″ (this corresponds to 0.25 pc for a source at the distance of Cas A). The ample frequency coverage allows us separate the relative contributions from the absorbing gas, the unabsorbed front of the shell, and the absorbed back of the shell to the emission spectrum. We explored the effects that a temperature lower than the ~100–500 K proposed from infrared observations and a high degree of clumping can have on the derived physical properties of the unshocked material, such as its mass and density. We also compiled integrated radio flux density measurements, fit for the absorption processes that occur in the radio band, and considered their effect on the secular decline of the source. Results. We find a mass in the unshocked ejecta of M = 2.95 ± 0.48 M⊙ for an assumed gas temperatureof T = 100 K. This estimate is reduced for colder gas temperatures and, most significantly, if the ejecta are clumped. We measure the reverse shock to have a radius of 114″± 6″ and be centred at 23:23:26, +58:48:54 (J2000). We also find that a decrease in the amount of mass in the unshocked ejecta (as more and more material meets the reverse shock and heats up) cannot account for the observed low-frequency behaviour of the secular decline rate. Conclusions. To reconcile our low-frequency absorption measurements with models that reproduce much of the observed behaviour in Cas A and predict little mass in the unshocked ejecta, the ejecta need to be very clumped or the temperature in the cold gas needs to be low (~10 K). Both of these options are plausible and can together contribute to the high absorption value that we find.
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