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Dr. Anna Julia Cooper was born into slavery at a time, when the 1831 Act prohibited the teaching of literacy to enslaved people in North Carolina in order to prevent rebellion and emancipation. Despite this, she was the fourth (known) Black female Ph.D. and the first African American woman to receive a doctorade from the Sorbonne University. She is still considered a mother of Black feminism and a formidable writer, activist, and educator.

Embryo development of sediment-dwelling amphipod Monoporeia affinis is sensitive to contaminant exposure. Therefore, embryo aberrations in gravid females are used to detect the biological effects of contaminant exposure in the Baltic Sea benthic habitats. The indicator based on the aberration frequencies in wild populations (ReproIND) is currently used for environmental status assessment within the Marine Strategy Framework Directive, Descriptor 8.2. However, so far, it has mainly been applied in the Bothnian Sea (BoS) and the Western Gotland Basin (WGB), where it was found to respond to contaminant pressure and non-chemical environmental factors, such as temperature.To expand the applicability of the indicator to other Baltic Sea basins, we used field data from the gulfs of Finland and Riga, BoS, and WGB to investigate the relationships between reproductive disorders and contaminants and environmental factors, thus evaluating the indicator suitability in these areas. Despite the natural variability of the environments and contaminant distribution across and within the basins, we found that high concentrations of contaminants, e.g. metals, PAHs, and PCBs, contribute significantly to the embryo aberrations in M. affinis. These findings support ReproIND applicability in the Baltic Sea and, perhaps, in other marine areas.

BackgroundCoronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis.MethodsWe analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression.ResultsIn 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome.ConclusionsMortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.

Abstract Background Invasive breast cancer patients are increasingly being treated with neoadjuvant chemotherapy; however, only a fraction of the patients respond to it completely. To prevent overtreatment, there is an urgent need for biomarkers to predict treatment response before administering the therapy. Methods In this retrospective study, we developed hypothesis-driven interpretable biomarkers based on deep learning, to predict the pathological complete response (pCR, i.e., the absence of tumor cells in the surgical resection specimens) to neoadjuvant chemotherapy solely using digital pathology H&E images of pre-treatment breast biopsies. Our approach consists of two steps: First, we use deep learning to characterize aspects of the tumor micro-environment by detecting mitoses and segmenting tissue into several morphology compartments including tumor, lymphocytes and stroma. Second, we derive computational biomarkers from the segmentation and detection output to encode slide-level relationships of components of the tumor microenvironment, such as tumor and mitoses, stroma, and tumor infiltrating lymphocytes (TILs). Results We developed and evaluated our method on slides from n = 721 patients from three European medical centers with triple-negative and Luminal B breast cancers and performed external independent validation on n = 126 patients from a public dataset. We report the predictive value of the investigated biomarkers for predicting pCR with areas under the receiver operating characteristic curve between 0.66 and 0.88 across the tested cohorts. Conclusion The proposed computational biomarkers predict pCR, but will require more evaluation and finetuning for clinical application. Our results further corroborate the potential role of deep learning to automate TILs quantification, and their predictive value in breast cancer neoadjuvant treatment planning, along with automated mitoses quantification. We made our method publicly available to extract segmentation-based biomarkers for research purposes.

Abstract Background Minimally invasive pancreatoduodenectomy (MIPD) aims to reduce the negative impact of surgery as compared to open pancreatoduodenectomy (OPD) and is increasingly becoming part of clinical practice for selected patients worldwide. However, the safety of MIPD remains a topic of debate and the potential shorter time to functional recovery needs to be confirmed. To guide safe implementation of MIPD, large-scale international randomized trials comparing MIPD and OPD in experienced high-volume centers are needed. We hypothesize that MIPD is non-inferior in terms of overall complications, but superior regarding time to functional recovery, as compared to OPD. Methods/design The DIPLOMA-2 trial is an international randomized controlled, patient-blinded, non-inferiority trial performed in 14 high-volume pancreatic centers in Europe with a minimum annual volume of 30 MIPD and 30 OPD. A total of 288 patients with an indication for elective pancreatoduodenectomy for pre-malignant and malignant disease, eligible for both open and minimally invasive approach, are randomly allocated for MIPD or OPD in a 2:1 ratio. Centers perform either laparoscopic or robot-assisted MIPD based on their surgical expertise. The primary outcome is the Comprehensive Complication Index (CCI®), measuring all complications graded according to the Clavien-Dindo classification up to 90 days after surgery. The sample size is calculated with the following assumptions: 2.5% one-sided significance level (α), 80% power (1-β), expected difference of the mean CCI® score of 0 points between MIPD and OPD, and a non-inferiority margin of 7.5 points. The main secondary outcome is time to functional recovery, which will be analyzed for superiority. Other secondary outcomes include post-operative 90-day Fitbit™ measured activity, operative outcomes (e.g., blood loss, operative time, conversion to open surgery, surgeon-reported outcomes), oncological findings in case of malignancy (e.g., R0-resection rate, time to adjuvant treatment, survival), postoperative outcomes (e.g., clinically relevant complications), healthcare resource utilization (length of stay, readmissions, intensive care stay), quality of life, and costs. Postoperative follow-up is up to 36 months. Discussion The DIPLOMA-2 trial aims to establish the safety of MIPD as the new standard of care for this selected patient population undergoing pancreatoduodenectomy in high-volume centers, ultimately aiming for superior patient recovery. Trial registration ISRCTN27483786. Registered on August 2, 2023

Abstract Background Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs. Methods The ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs. Discussion The ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. Trial registration International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021.

A diagnostic medical tool is described that allows patients to non-invasively observe, describe and document their own retinal blood vessels using the Purkinje vascular entoptic test. We envision key applications of the Purkinje retinal image stabilization (PRIS) device in monitoring of diabetic retinopathy and cost-effective assessment of retinal visual acuity. To optimize our PRIS principle, we have developed a benchtop device with interchangeable light modules. The modular design is intended to provide maximum flexibility for determining appropriate PRIS stimulation parameters. In self-tests, we found that a pleasant entoptic perception occurs when a green luminous light spot (approx. 525 nm) moves on a circular path. The challenging part is to derive an objective diagnosis from a subjective phenomenon.

Abstract Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23–1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03–0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30–3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24–87%), 71% (95% CI 48–100%) and 88% (95% CI 74–100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069.

BackgroundPatients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes.MethodsThe European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage.ResultsAmong 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2-7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage.ConclusionsThis study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic.

Abstract Background The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab. Methods From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups. Results BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36–4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25–0.80) and BCSS (aHR 0.46, 95% CI 0.24–0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes. Conclusions In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.

Abstract Ductal carcinoma in-situ (DCIS) accounts for 20–25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.

BackgroundObservational studies in metastatic breast cancer (MBC) show that long-term overall survival (OS) is associated with limited tumor burden, or oligo-MBC (OMBC). However, a uniform definition of OMBC is lacking. In this real-world nationwide cohort, we aimed to define the optimal OMBC threshold and factors associated with survival in patients with OMBC.Methods3535 patients aged younger than 80 years at diagnosis of de novo MBC in the Netherlands between January 2000 and December 2007 were included. Detailed clinical, therapy, and outcome data were collected from medical records of a sample of the patients. Using inverse-sampling-probability weighting, the analysis cohort (n = 3447) was constructed. We assessed OS according to number of metastases at diagnosis to determine the optimal OMBC threshold. Next, we applied Cox regression models with inverse-sampling-probability weighting to study associations with OS and progression-free survival in OMBC. All statistical tests were 2-sided.ResultsCompared with more than 5 distant metastases, adjusted hazard ratios for OS (with 95% confidence interval [CI] based on robust standard errors) for 1, 2-3, and 4-5 metastases were 0.70 (95% CI = 0.52 to 0.96), 0.63 (95% CI = 0.45 to 0.89), and 0.91 (95% CI = 0.61 to 1.37), respectively. Ten-year OS estimates for patients with no more than 3 vs more than 3 metastases were 14.9% and 3.4% (P

Abstract Immune checkpoint blockade (ICB) is currently approved for patients with triple-negative breast cancer (TNBC), whereas responses to ICB are also observed in a small subgroup of Estrogen Receptor (ER)-positive breast cancer. The cut-off for ER-positivity (≥1%) is based on likelihood of endocrine treatment response, but ER-positive breast cancer represents a very heterogeneous group. This raises the question whether selection based on ER-negativity should be revisited to select patients for ICB treatment in the context of clinical trials. Stromal tumor-infiltrating lymphocytes (sTILs) and other immune parameters are higher in TNBC compared to ER-positive breast cancer, but it is unknown whether lower ER levels are associated with more inflamed tumor microenvironments (TME). We collected a consecutive series of primary tumors from 173 HER2-negative breast cancer patients, enriched for tumors with ER expression between 1 and 99% and found levels of stromal TILs, CD8 + T cells, and PD-L1 positivity in breast tumors with ER 1–9% and ER 10–50% to be comparable to tumors with ER 0%. Expression of immune-related gene signatures in tumors with ER 1–9% and ER 10–50% was comparable to ER 0%, and higher than in tumors with ER 51–99% and ER 100%. Our results suggest that the immune landscape of ER low tumors (1–9%) and ER intermediate tumors (10–50%) mimic that of primary TNBC.

Key Clinical Message Thrombotic microangiopathies are a side effect of anti‐VEGF therapies, which are often limited to the kidneys but can also occur systemically and be life‐threatening. Screening for increasing proteinuria is essential. Abstract We present the case of a 65‐year‐old male patient with a multifocal HCC, Barcelona clinic liver cancer (BCLC) classification B at the time of diagnosis. The HCC was treated with nine sessions of transarterial chemoembolization (TACE), and after a progress, the therapy was switched to a combination of atezolizumab and bevacizumab. Five months after therapy change, he presented with an acute kidney injury. The histopathology of the renal biopsy showed findings of a thrombotic microangiopathy (TMA), which we treated with 12 sessions of therapeutic plasma exchange in combination with steroids, resulting in a decreased TMA activity and later in a remission of the TMA. This case suggests the importance of monitoring the kidney function and proteinuria in patients under anti‐vascular endothelial growth factor (VEGF) therapy and shows a rare differential diagnosis for a worsening of kidney function in these patients. Furthermore, it shows that therapeutic plasma exchange might be a valuable therapeutic option for patients with TMA due to anti‐VEGF therapy.

The Gulf of Riga is a relatively shallow bay connected to the deeper central Baltic Sea (Baltic Proper) via straits with sills. The decrease in the near-bottom oxygen levels from spring to autumn is a common feature in the gulf, but in 2018, extensive hypoxia was observed. We analyzed temperature, salinity, oxygen, and nutrient data collected in 2018, along with historical data available from environmental databases. Meteorological and hydrological data from the study year were compared with their long-term means and variability. We suggest that pronounced oxygen depletion occurred in 2018 due to a distinct development of vertical stratification. Seasonal stratification developed early and was stronger in spring–summer 2018 than on average due to high heat flux and weak winds. Dominating northeasterly winds in early spring and summer supported the inflow of saltier waters from the Baltic Proper that created an additional deep pycnocline restricting vertical transport between the near-bottom layer (NBL) and the water column above. The estimated oxygen consumption rate in the NBL in spring–summer 2018 was about 1.7 mmolO2m-2h-1, which exceeded the oxygen input to the NBL due to advection and vertical mixing. Such a consumption rate leads to near-bottom hypoxia in all years when vertical mixing in autumn reaches the seabed later than on average according to the long-term (1979–2018) meteorological conditions. The observed increase in phosphate concentrations in the NBL in summer 2018 suggests a significant sediment phosphorus release in hypoxic conditions counteracting the mitigation measures to combat eutrophication. Since climate change projections predict that meteorological conditions comparable to those in 2018 will occur more frequently, extensive hypoxia would be more common in the Gulf of Riga and other coastal basins with similar morphology and human-induced elevated input of nutrients.

The risk of a zoonotic pandemic disease threatens hundreds of millions of people. Emerging infectious diseases also threaten livestock and wildlife populations around the world and can lead to devastating economic damages. China and the USA-due to their unparalleled resources, widespread engagement in activities driving emerging infectious diseases and national as well as geopolitical imperatives to contribute to global health security-play an essential role in our understanding of pandemic threats. Critical to efforts to mitigate risk is building upon existing investments in global capacity to develop training and research focused on the ecological factors driving infectious disease spillover from animals to humans. International cooperation, particularly between China and the USA, is essential to fully engage the resources and scientific strengths necessary to add this ecological emphasis to the pandemic preparedness strategy. Here, we review the world's current state of emerging infectious disease preparedness, the ecological and evolutionary knowledge needed to anticipate disease emergence, the roles that China and the USA currently play as sources and solutions to mitigating risk, and the next steps needed to better protect the global community from zoonotic disease.

The Representation of the Postwar Period in Zita Szeleczky’s Press Appearances, Lawsuit and Private Letters From 1936 to 1944, the Hungarian star world created a unique tabloid environment in both the print press and film production. Zita Szeleczky (1905–1999), one of the most popular Hungarian actresses of the 1930s and 1940s, was on the one hand called the little sister of the nation, and on the other hand, politically stigmatised on several occasions for her clumsy career planning and self-expression. The latter was due to the fact that, from the first years of the Second World War onwards, the actress made a number of objectionable decisions out of naivety, vanity or resentment. Her death was reported in the printed press and she was condemned as a war criminal in absentia. In the present study, we have not sought to comment on any of this, but have merely supplemented the factual information available in the press and in the People’s Court documents with relevant details from the private correspondence of 1946 and 1947, which illustrate the experiences and opinions of the actress and her colleagues. Zita Szeleczky’s career and fate were shattered, and she had to start her life anew during the post-war years. As a result of our research, it can be concluded that the main details of the actress’s character assassination were drawn from the antecedents of Zita Szeleczky’s People’s Court trial, from the articles examined in chronological order in 1945 and from the trial material. In addition, the post-war condition is reflected in several examples of Zita Szeleczky’s private correspondence from the period under study. Following her character assassination, her break with fate – the trauma she had suffered – she must have continued to fear that Italy would extradite her to Hungary and would have to execute her sentence. She also tried, partly with her colleagues and partly on her own, to launch her international career, which was not initially very successful, mainly due to post-war tensions in 1946 and 1947.

Two new sympatric isopod species of the genus Castellanethes (Olibrinidae) are described from caves located in the Western High Atlas of Morocco. Both species present troglomorphic traits, such as the absence of body pigmentation and eyes and are, therefore, considered cave-dwelling species (troglobitic). Castellenethes ougougensis sp. nov. was found in five caves, while C. ighousi sp. nov. is an amphibious species found in only two caves, which also harbour populations of C. ougougensis sp. nov. Additionally, notes on their habitats are provided, as well as a discussion on their conservation status.

Abstract Background Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C. Methods/design Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality. Discussion PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente et al., 2007; Bassi et al., 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., 2016; Pratt et al., 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., 2022; Asbun and Stauffer, 2011).

Summary: Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of −7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI −6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0–30.0] vs 23.0 [14.0–32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0–30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5–5.5] vs 5 [95% CI 4.7–5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67–1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.

Objectives To assess the sensitivity and specificity of the 2019 EULAR/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) in outpatients at an academic tertiary care centre and to compare them to the 1997 ACR and the 2012 Systemic Lupus International Collaborating Clinics criteria.Methods Prospective and retrospective observational cohort study.Results 3377 patients were included: 606 with SLE, 1015 with non-SLE autoimmune-mediated rheumatic diseases (ARD) and 1756 with non-ARD diseases (hepatocellular carcinoma, primary biliary cirrhosis, autoimmune hepatitis). The 2019 criteria were more sensitive than the 1997 criteria (87.0% vs 81.8%), but less specific (98.1% vs 99.5% in the entire cohort and 96.5% vs 98.8% in patients with non-SLE ARD), resulting in Youden Indexes for patients with SLE/non-SLE ARD of 0.835 and 0.806, respectively. The most sensitive items were history of antinuclear antibody (ANA) positivity and detection of anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies. These were also the least specific items. The most specific items were class III/IV lupus nephritis and the combination of low C3 and low C4 complement levels, followed by class II/V lupus nephritis, either low C3 or low C4 complement levels, delirium and psychosis, when these were not attributable to non-SLE causes.Conclusions In this cohort from an independent academic medical centre, the sensitivity and specificity of the 2019 lupus classification criteria were confirmed. Overall agreement of the 1997 and the 2019 criteria was very good.