Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Evaluating persistent T1-weighted lesions without concurrent abnormal enhancement on breast MRI in neoadjuvant chemotherapy patients: implications for complete pathological response.

OBJECTIVE: This study aims to determine whether persistent T1-weighted lesions signify a complete pathological response (pCR) in breast cancer patients treated with neoadjuvant chemotherapy and surgery, and to evaluate their correlation with imaging responses on MRI. MATERIALS AND METHODS: A retrospective review was conducted on data from breast cancer patients treated between January 2011 and December 2018. Patients who underwent breast MRI and pre- and post-neoadjuvant chemotherapy followed by surgery were included. Those with distant metastasis, no planned surgery, pre-surgery radiation, ineligibility for neoadjuvant chemotherapy, or unavailable surgical pathology were excluded. Groups with and without persistent T1-weighted lesions were compared using the chi-square test for categorical variables and the Student t test or Wilcox rank sum test for continuous variables. Univariate logistic regression was used to evaluate the association of the final pathological response with the presence of T1-persistent lesion and other characteristics. RESULTS: Out of 319 patients, 294 met the inclusion criteria (breast cancer patients treated with neoadjuvant chemotherapy and subsequent surgery); 157 had persistent T1 lesions on post-chemotherapy MRI and 137 did not. A persistent T1 lesion indicated reduced likelihood of complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). Multivariable analysis confirmed these findings: OR 0.37 (95% CI 0.18-0.76), p = 0.007. No other characteristics correlated with T1 residual lesions. CONCLUSION: Persistent T1-weighted lesions without associated abnormal enhancement on post-treatment breast MRI correlate with lower complete pathological and imaging response rates. CLINICAL RELEVANCE STATEMENT: The study underscores the importance of persistent T1-weighted lesions on breast MRI as vital clinical markers, being inversely related to a complete pathological response following neoadjuvant chemotherapy; they should be a key factor in guiding post-neoadjuvant chemotherapy treatment decisions. KEY POINTS: • Persistent T1 lesions on post-chemotherapy breast MRI indicate a reduced likelihood of achieving a complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). • Through multivariable analysis, it was confirmed that the presence of a persistent T1 lesion on breast MRI post-chemotherapy is linked to a decreased likelihood of complete pathological response, with an odds ratio (OR) of 0.37 (95% CI 0.18-0.76; p = 0.007). • In addition to the convention of equating the absence of residual enhancement to complete imaging response, our results suggest that the presence or absence of residual T1 lesions should also be considered.

Quality of Recovery After Unplanned and Planned Cesarean Deliveries: A Prospective Observational Study Using the Obstetric Quality of Recovery-10 Tool.

BACKGROUND: There is a paucity of literature examining the differences between patient-reported outcome measures after planned and unplanned cesarean delivery using a validated quality of recovery tool. The Obstetric Quality of Recovery-10 (ObsQoR-10) scoring tool has been validated to quantify functional recovery after cesarean delivery. We aimed to use the ObsQoR-10 to compare the postoperative recovery characteristics of patients undergoing planned and unplanned cesarean deliveries. METHODS: We conducted a prospective single-center observational study. Patients undergoing planned and unplanned cesarean deliveries under neuraxial anesthesia were asked to complete the ObsQoR-10 questionnaire 24 hours, 48 hours, and 1 week postpartum. We collected information on total in-hospital postoperative opioid consumption and patients´ perception of readiness for discharge at 24 and 48 hours postpartum. Additionally, patient characteristics were collected to assess their correlation with our findings. RESULTS: We included 112 patients (56 in each group). No statistical differences in ObsQoR-10 scores at 24 hours, 48 hours, and 1 week postpartum were observed between the planned and unplanned cesarean deliveries. Additionally, there was no difference between the groups in patients' perception of readiness for hospital discharge at 24 and 48 hours and opioid consumption in the first 2 days after surgery. Most patients in both groups did not think they would be ready for discharge at 24 hours postpartum. Analysis of the individual components of ObsQoR-10 at 24 hours showed a difference in the responses assessing the severity of shivering (higher in unplanned cesarean deliveries) and the ability to look after personal hygiene (lower in unplanned cesarean deliveries). CONCLUSIONS: As assessed by the ObsQoR-10, no significant difference in the quality of recovery was observed between patients undergoing planned and unplanned cesarean delivery.

Radiomics-based distinction of small (≤2 cm) hepatocellular carcinoma and precancerous lesions based on unenhanced MRI.

AIM: To assess the feasibility of a radiomics model based on unenhanced magnetic resonance imaging (MRI) to differentiate small hepatocellular carcinoma (S-HCC) (≤2 cm) and pre-hepatocellular carcinoma (Pre-HCC). MATERIALS AND METHODS: One hundred and fourteen histopathologically confirmed 114 hepatic nodules were analysed retrospectively. All patients had undergone MRI before surgery using a 3 T MRI system. Each nodule was segmented on unenhanced MRI sequences (T1-weighted imaging [T1] and T2WI with fat-suppression [FS-T2]). Radiomics features were extracted and the optimal features were selected using the least absolute shrinkage and selection operator (LASSO). The support vector machine (SVM) was used to establish the radiomics model. One abdominal radiologist performed the conventional qualitative analysis for classification of S-HCC and Pre-HCC. The diagnostic performances of the radiomics and radiologist models were evaluated using receiver operating characteristic (ROC) analysis. RESULT: Radiomics features (n=1,223) were extracted from each sequence and the optimal features were selected from T1, FS-T2, and T1+FS-T2 to construct the radiomics models. The radiomics model based on T1+FS-T2 showed the best performance among the three models, with areas under the ROC curves (AUCs) of 0.95 (95 % confidence interval [CI], 0.875-0.986) and 0.942 (95 % CI, 0.775-0.985), accuracies of 86 % and 88.5 %, sensitivities of 94.12 % and 100 %, and specificities of 85.48 % and 85.19 %, respectively. The radiomics model on FS-T2 showed better performance on a single sequence than that of the T1-based model. The diagnostic performance for the radiomic model was significantly higher than that for the radiologist (AUC = 0.518, p<0.05). CONCLUSION: This study suggested that a radiomics model based on unenhanced MRI may serve as a feasible and non-invasive tool to classify S-HCC and Pre-HCC.

Association of serum lipids and abnormal lipid score with cancer risk: a population-based prospective study.

BACKGROUND: Serum lipid levels are associated with cancer risk. However, there still have uncertainties about the single and combined effects of low lipid levels on cancer risk. METHODS: A prospective cohort study of 33,773 adults in Shanghai between 2016 and 2017 was conducted. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured. Cox proportional hazard models were used to assess the association of single and combined lipids with overall, lung, colon, rectal, thyroid gland, stomach, and female breast cancers. The effect of the combination of abnormal lipid score and lifestyle on cancer was also estimated. RESULTS: A total of 926 incident cancer cases were identified. In the RCS analysis, hazard ratios (HRs) of overall cancer for individuals with TC < 5.18 mmol/L or with LDL-C < 3.40 mmol/L were higher. Low TC was associated with higher colorectal cancer risk (HR [95% CI] = 1.76 [1.09-2.84]) and low HDL-C increased thyroid cancer risk by 90%. Abnormal lipid score was linearly and positively associated with cancer risk, and smokers with high abnormal lipid scores had a higher cancer risk, compared to non-smokers with low abnormal lipid scores (P < 0.05). CONCLUSIONS: Low TC levels were associated with an increased risk of overall and colorectal cancer. More attention should be paid to participants with high abnormal lipid scores and unhealthy lifestyles who may have a higher risk of developing cancer. Determining the specific and comprehensive lipid combinations that affect tumorigenesis remains a valuable challenge.

Differential sensory block during labour epidural analgesia: a prospective observational study to investigate the relationship of lower and upper sensory block levels to cold, pinprick, and light touch.

PURPOSE: A zone of differential block to cold has been recently documented during labour epidural analgesia, with an upper sensory block level (USBL) and a lower sensory block level (LSBL). We aimed to determine the correlation between USBL and LSBL to cold and pinprick and sensory block level to light touch during labour epidural analgesia. METHODS: We conducted a prospective observational study in patients requesting labour epidural analgesia. We placed an epidural catheter at L2/L3 or L3/L4, followed by a programmed intermittent epidural bolus plus patient-controlled epidural analgesia regimen. We assessed the sensory block levels 140 min after administering the loading dose. The primary outcomes were the USBL and LSBL to cold and pinprick and the sensory block level to light touch. RESULTS: We studied 30 patients. The median [interquartile range (IQR)] USBL and LSBL to ice were T7 [T7-T6] and T9 [T10-T8], respectively. The median [IQR] USBL and LSBL to pinprick were T8 [T10-T6] and T10 [T12-T10], respectively. There was a strong correlation between USBL to ice and pinprick (Spearman correlation coefficient, 0.57) and between LSBL to ice and pinprick (Spearman correlation coefficient, 0.52). There was no significant correlation between sensory block level to light touch and either USBL or LSBL to ice or pinprick. CONCLUSION: We observed two sensory block levels to ice and pinprick. Further studies are required to understand if one modality-cold or pinprick-is superior to the other in assessing sensory block levels in this context. Light touch is unreliable as a modality of sensory block assessment during labour epidural analgesia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05187962); registered 12 January 2022.

RéSUMé: OBJECTIF: Une zone de bloc différentiel de réaction au froid a récemment été documentée pendant l'analgésie péridurale obstétricale, avec un niveau de bloc sensoriel supérieur (USBL, pour upper sensory block level) et un niveau de bloc sensoriel inférieur (LSBL, pour lower sensory block level). Notre objectif était de déterminer la corrélation entre l'USBL et le LSBL au contact du froid et de la piqûre et le niveau de bloc sensoriel au toucher léger pendant l'analgésie péridurale obstétricale. MéTHODE: Nous avons mené une étude observationnelle prospective chez des patient·es demandant une analgésie péridurale obstétricale. Nous avons placé un cathéter péridural au niveau L2/L3 ou L3/L4, suivi d'une administration programmée de bolus périduraux plus un régime d'analgésie péridurale contrôlée par le/la patient·e. Nous avons évalué les niveaux de bloc sensoriel 140 min après l'administration de la dose de charge. Les critères d'évaluation principaux étaient l'USBL et le LSBL en réaction au froid et à la piqûre d'épingle et le niveau de bloc sensoriel en réaction au toucher léger. RéSULTATS: Nous avons étudié 30 patient·es. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la glace étaient situés au niveau T7 [T7-T6] et T9 [T10-T8], respectivement. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la piqûre étaient localisés au niveau T8 [T10­T6] et T10 [T12­T10], respectivement. Il y avait une forte corrélation entre l'USBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,57) et entre le LSBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,52). Il n'y avait pas de corrélation significative entre le niveau de bloc sensoriel en réaction au toucher léger et l'USBL ou le LSBL en réaction à la glace ou à la piqûre. CONCLUSION: Nous avons observé deux niveaux de bloc sensoriel à la glace et à la piqûre. D'autres études sont nécessaires pour comprendre si une modalité ­ le froid ou la piqûre ­ est supérieure à l'autre pour évaluer les niveaux de bloc sensoriel dans ce contexte. Le toucher léger n'est pas fiable en tant que modalité d'évaluation du bloc sensoriel pendant l'analgésie péridurale obstétricale. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05187962); enregistré le 12 janvier 2022.

Weight stigma from romantic partners: Its relations with maladaptive and adaptive coping and depressive symptoms.

Social devaluation of being overweight is common in daily life, but little is known about the weight stigma in romantic relationships. The present study investigated the roles of maladaptive and adaptive coping strategies in the relation between the experience of weight stigma in romantic relationships and depressive symptoms in men and women, respectively. Analyses of gender differences and structural equation modeling yielded several findings. First, while men and women experienced similar levels of weight stigma from their romantic partners, women were more likely to use exercise avoidance, disengagement coping, and reappraisal coping strategies, and to exhibit more depressive symptoms than men. Second, men who experienced weight stigma tended to cope with it through exercise avoidance and disengagement coping, which were related to greater depressive symptoms. Men also coped with weight stigma adaptively via reappraisal coping, which was additionally associated with more positive affect. Third, the relation between the experience of weight stigma and depressive symptoms in women was only explained by using disengagement coping. These findings extend the understanding of weight stigma to a specific context and provide some insight that future interventions to reduce the impacts of weight stigma should be tailored accordingly for men and women.

[Statistical analysis of disability-adjusted life years for stomach and colorectal cancers in Changning District of Shanghai].

Objectives: To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district. Methods: Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods. Results: The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/105 and 597.51/105, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions: The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

[The impact of gallbladder cholesterolosis on the morphology of gallstones].

Objective: To investigate the impact of gallbladder cholesterolosis on the morphology of gallstones. Methods: The patients with gallstone who underwent cholecystectomy at the Gallstone Disease Center of East Hospital Affiliated to Tongjin University from December 2020 to October 2021 were retrospectively included. The patients were divided into the case group (sludge-like) and the control group (non-sludge-like stone), based on gallstone morphology. Clinical baseline characteristics between the two groups were compared. The related factors influencing gallstone morphology were analyzed using multivariate logistic regression analysis. Results: A total of 110 patients were included, with 30 cases in the case group (13 males, 17 females), aged 26-73 (54±14) years, 80 cases in the control group (24 males, 56 females), aged 18-75 (45±13) years. The age of the case group was higher than that of the control group (P=0.003). The occurrence rate of occult pancreaticobiliary reflux (OPBR) was higher in the case group compared to the control group [33.3% (10/30) vs 13.8% (11/80), P=0.020]; the occurrence rate of gallbladder cholesterolosis was lower in the case group compared to the control group [30.0% (9/30) vs 73.8% (59/80), P<0.001]. The results of multivariate logistic regression analysis showed that gallbladder cholesterolosis (OR=0.19, 95%CI: 0.07-0.49, P=0.001) was a significant factor associated with sludge-like stones. Conclusion: Gallbladder cholesterolosis can cause the formation of different forms of cholecystolithiasis, and promote the occurrence and development of "solid stones".

[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Renal ischemia alters the transcriptomic and epigenetic profile of inflammatory genes in swine scattered tubular-like cells.

BACKGROUND: Scattered tubular-like cells (STCs) are differentiated renal tubular cells that during recovery from ischemic injury dedifferentiate to repair other injured renal cells. Renal artery stenosis (RAS), often associated with chronic inflammatory injury, compromises the integrity and function of STCs, but the underlying mechanisms remain unknown. We hypothesized that RAS alters the transcriptomic and epigenetic profile of inflammatory genes in swine STCs. METHODS: STCs were harvested from pig kidneys after 10 weeks of RAS or sham (n=6 each). STC mRNA profiles of inflammatory genes were analyzed using high-throughput mRNA-sequencing (seq) and their DNA methylation (5mC) and hydroxymethylation (5hmC) profiles by DNA immunoprecipitation and next-generation sequencing (MeDIP-seq) (n=3 each), followed by an integrated (mRNA-seq/MeDIP-seq) analysis. STC protein expression of candidate differentially expressed (DE) genes and common proinflammatory proteins were subsequently assessed in vitro before and after epigenetic (Bobcat339) modulation. RESULTS: mRNA-seq identified 57 inflammatory genes up-regulated in RAS-STCs versus Normal-STCs (>1.4 or <0.7-fold, P<0.05), of which 14% exhibited lower 5mC and 5% higher 5hmC levels in RAS-STCs versus Normal-STCs, respectively. Inflammatory gene and protein expression was higher in RAS-STCs compared with Normal-STCs but normalized after epigenetic modulation. CONCLUSIONS: These observations highlight a novel modulatory mechanism of this renal endogenous repair system and support development of epigenetic or anti-inflammatory therapies to preserve the reparative capacity of STCs in individuals with RAS.

Clinical impact of less invasive surfactant administration using video laryngoscopy in extremely preterm infants.

BACKGROUND: Examine the real-world clinical impact of adopting less invasive surfactant administration (LISA) as the primary surfactant administration method in extremely preterm infants. METHODS: Single-center pre-post cohort study conducted over a 4-year period comparing outcomes of spontaneously breathing inborn infants 24+0-28+6 weeks gestational age (GA) receiving surfactant via endotracheal tube (pre-cohort, n = 154) or LISA via thin catheter (post-cohort, n = 70). Primary outcome was need for invasive mechanical ventilation (IMV, ≥2 h) ≤72 h of age. Secondary outcomes were a composite of mortality, bronchopulmonary dysplasia, intraventricular hemorrhage ≥grade 3 or necrotizing enterocolitis, and its individual components. Groups were compared using propensity score methods, including covariates: GA, birth weight, sex, small for GA, SNAP II ≥20, premature rupture of membranes, maternal hypertension/diabetes, and C-section. RESULTS: GA and birth weight were 27.1 (26, 28.1) weeks and 914 (230) g, and 27.1 (26.1, 28.1) weeks and 920 (236) g for pre- and post-cohorts, respectively. Pre-cohort had higher C-section rates, (67% vs. 51%, p = 0.03). After adjustment for covariates, LISA was associated with reduced IMV exposure [AOR (95% CI) 0.07 (0.04, 0.11)], lower odds of the composite clinical outcome [0.49 (0.33, 0.73)], and most of its individual components. CONCLUSION: Real-world experience favors LISA as the primary method in extremely preterm infants with established spontaneous respiration. IMPACT: Less invasive surfactant administration (LISA) is associated with a reduction in respiratory morbidity, but real-world data of routine use among extremely preterm infants are limited. LISA is associated with reduced frequency of exposure to and duration of IMV in both ≤72 h after birth and during hospital stay. LISA is associated with a reduction in mortality, and most other major morbidities including bronchopulmonary dysplasia, and interventricular hemorrhage. Data from a large North American center providing real-world clinical outcomes following LISA as the primary method of surfactant administration.

Organ dysfunction and mortality in preterm neonates with late-onset bloodstream infection.

BACKGROUND: Organ dysfunction (ODF) in late-onset bloodstream infection (LBSI) is associated with increased risk of adverse outcomes. However, no established definition of ODF exists among preterm neonates. Our objective was to describe an outcome-based ODF definition for preterm infants, and assess factors associated with mortality. METHODS: This is a six-year retrospective study of neonates <35 weeks gestational age, >72 h of age, with non-CONS bacterial/fungal LBSI. Discriminatory ability of each parameter for mortality was evaluated: base deficit ≤-8 mmol/L (BD8), renal dysfunction (urine output <1 cc/kg/h or creatinine ≥100 µmol/L), hypoxic respiratory failure (HRF, ventilated, FiO2 = 1.0), or vasopressor/inotrope use (V/I). Multivariable logistic regression analysis was performed to derive a mortality score. RESULTS: One hundred and forty-eight infants had LBSI. BD8 had the highest individual predictive ability for mortality (AUROC = 0.78). The combination BD8 + HRF + V/I was used to define ODF (AUROC = 0.84). Fifty-seven (39%) infants developed ODF, among which 28 (49%) died. Mortality increased inversely relative to GA at LBSI-onset (aOR 0.81 [0.67, 0.98]) and directly relative to ODF occurrence (12.15 [4.48, 33.92]). Compared to no-ODF, ODF infants had lower GA and age at illness, and higher frequency of Gram-negative pathogen. CONCLUSIONS: Among preterm neonates with LBSI, significant metabolic acidosis, HRF, and vasopressor/inotrope use may identify infants high risk for mortality. These criteria could help identify patients for future studies of adjunctive therapies. IMPACT: Sepsis-related organ dysfunction is associated with increased risk of adverse outcomes. Among preterm neonates, significant metabolic acidosis, use of vasopressors/inotropes, and hypoxic respiratory failure may identify high-risk infants. This can be used to target research and quality improvement efforts toward the most vulnerable infants.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

PURPOSE: We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). METHODS: From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. RESULTS: Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). CONCLUSION: The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

Anatomical and surgical characteristics correlate with pachymeningeal failure in patients with brain metastases after neurosurgical resection and adjuvant stereotactic radiosurgery.

PURPOSE: Neurosurgery (NS) is an essential modality for large brain metastases (BM). Postoperative stereotactic radiosurgery (SRS) is the standard of care adjuvant treatment. Pachymeningeal failure (PMF) is a newly described entity, distinct from classical leptomeningeal failure (LMF), that is uniquely observed in postoperative patients treated with adjuvant SRS. We sought to identify risk factors for PMF in patients treated with NS + SRS. METHODS: From a prospective registry (2009 to 2021), we identified all patients treated with NS + SRS. Clinical, imaging, pathological, and treatment factors were analyzed. PMF incidence was evaluated using a competing risks model. RESULTS: 144 Patients were identified. The median age was 62 (23-90). PMF occurred in 21.5% (31/144). Female gender [Hazard Ratio (HR) 2.65, p = 0.013], higher Graded Prognostic Assessment (GPA) index (HR 2.4, p < 0.001), absence of prior radiation therapy (HR N/A, p = 0.018), controlled extracranial disease (CED) (HR 3.46, p = 0.0038), and pia/dura contact (PDC) (HR 3.30, p = 0.0053) were associated with increased risk for PMF on univariate analysis. In patients with PDC, wider target volumes correlated with reduced risk of PMF. Multivariate analysis indicated PDC (HR 3.51, p = 0.0053), piecemeal resection (HR 2.38, p = 0.027), and CED (HR 3.97, p = 0.0016) independently correlated with PMF risk. PMF correlated with reduced OS (HR 2.90, p < 0.001) at a lower rate compared to LMF (HR 10.15, p < 0.001). CONCLUSION: PMF correlates with tumor PDC and piecemeal resection in patients treated with NS + SRS. For unclear reasons, it is also associated with CED. In tumors with PDC, wider dural radiotherapy coverage was associated with a lower risk of PMF.

Serous surface papillary borderline ovarian tumors: sonographic features with clinicopathological correlation.

Serous surface papillary borderline ovarian tumor (SSPBOT) is a distinct subtype of serous borderline ovarian tumor (SBOT) characterized by solid tissue deposition confined to the ovarian surface. Because SSPBOT is rare, there are few published reports on the ultrasonographic features of this condition. In this retrospective study, we investigated 12 cases of SSPBOT. Ultrasound of SSPBOT showed grossly normal ovaries that were partially or wholly encased with tumor deposits confined to the surface, and clear demarcation between normal ovarian tissue and surrounding tumors. Doppler sonography demonstrated the fireworks sign in all cases of SSPBOT, as an intratumoral vascular bundle originating from the ovarian vessels and supplying hierarchical branching blood flow to the surrounding tumor. No patients with ovarian high-grade serous carcinoma showed these characteristic morphological and Doppler features. In our series, the firework sign appeared to be a characteristic feature of SSPBOTs. Utilization of this novel marker may help to identify correctly SSPBOT. This article is protected by copyright. All rights reserved.

Dopamine or norepinephrine for sepsis-related hypotension in preterm infants: a retrospective cohort study.

The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born < 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality (< 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p > 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmH2O), heart rate (185 ± 17 vs. 175 ± 17 beats per minute), and median (IQR) fraction of inspired oxygen [0.67 (0.42, 1.0) vs. 0.52 (0.32, 0.82)] (p < 0.05 for all). After PS adjustment, NE was associated with lower episode-related mortality [adjusted odds ratio (95% CI) 0.55 (0.33, 0.92)], pre-discharge mortality [0.60 (0.37, 0.97)], post-illness new diagnosis of significant neurologic injury [0.32 (0.13, 0.82)], and subsequent occurrence of NEC/sepsis among the survivors [0.34, (0.18, 0.65)]. CONCLUSION: NE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents. WHAT IS KNOWN: •Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants. •For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock. WHAT IS NEW: •This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants. •Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis.

Pathogenic infection characteristics and risk factors for bovine respiratory disease complex based on the detection of lung pathogens in dead cattle in Northeast China.

Bovine respiratory disease complex (BRDC) involves multiple pathogens, shows diverse lung lesions, and is a major concern in calves. Pathogens from 160 lung samples of dead cattle from 81 cattle farms in Northeast China from 2016 to 2021 were collected to characterize the molecular epidemiology and risk factors of BRDC and to assess the major pathogens involved in bovine suppurative or caseous necrotizing pneumonia. The BRDC was diagnosed by autopsy, pathogen isolation, PCR, or reverse transcription-PCR detection, and gene sequencing. More than 18 species of pathogens, including 491 strains of respiratory pathogens, were detected. The positivity rate of bacteria in the 160 lung samples was 31.77%, including Trueperella pyogenes (9.37%), Pasteurella multocida (8.35%), Histophilus somni (4.48%), Mannheimia haemolytica (2.44%), and other bacteria (7.13%). The positivity rate of Mycoplasma spp. was 38.9%, including M. bovis (7.74%), M. dispar (11.61%), M. bovirhinis (7.94%), M. alkalescens (6.11%), M. arginini (0.81%), and undetermined species (4.68%). Six species of viruses were detected with a positivity rate of 29.33%, including bovine herpesvirus-1 (BoHV-1; 13.25%), bovine respiratory syncytial virus (BRSV; 5.50%), bovine viral diarrhea virus (BVDV; 4.89%), bovine parainfluenza virus type-3 (BPIV-3; 4.28%), bovine parainfluenza virus type-5 (1.22%), and bovine coronavirus (2.24%). Mixed infections among bacteria (73.75%), viruses (50%), and M. bovis (23.75%) were the major features of BRDC in these cattle herds. The risk analysis for multi-pathogen co-infection indicated that BoHV-1 and H. somni; BVDV and M. bovis, P. multocida, T. pyogenes, or Mann. haemolytica; BPIV-3 and M. bovis; BRSV and M. bovis, P. multocida, or T. pyogenes; P. multocida and T. pyogenes; and M. bovis and T. pyogenes or H. somni showed co-infection trends. A survey on molecular epidemiology indicated that the occurrence rate of currently prevalent pathogens in BRDC was 46.15% (6/13) for BoHV-1.2b and 53.85% (7/13) for BoHV-1.2c, 53.3% (8/15) for BVDV-1b and 46.7% (7/15) for BVDV-1d, 29.41% (5/17) for BPIV-3a and 70.59% (12/17) for BPIV-3c, 100% (2/2) for BRSV gene subgroup IX, 91.67% (33/36) for P. multocida serotype A, and 8.33% (3/36) for P. multocida serotype D. Our research discovered new subgenotypes for BoHV-1.2c, BRSV gene subgroup IX, and P. multocida serotype D in China's cattle herds. In the BRDC cases, bovine suppurative or caseous necrotizing pneumonia was highly related to BVDV [odds ratio (OR) = 4.18; 95% confidence interval (95% CI): 1.6-10.7], M. bovis (OR = 2.35; 95% CI: 1.1-4.9), H. somni (OR = 8.2; 95% CI: 2.6-25.5), and T. pyogenes (OR = 13.92; 95% CI: 5.8-33.3). The risk factor analysis found that dairy calves <3 mo and beef calves >3 mo (OR = 5.39; 95% CI: 2.7-10.7) were more susceptible to BRDC. Beef cattle were more susceptible to bovine suppurative or caseous necrotizing pneumonia than dairy cattle (OR = 2.32; 95% CI: 1.2-4.4). These epidemiological data and the new pathogen subgenotypes will be helpful in formulating strategies of control and prevention, developing new vaccines, improving clinical differential diagnosis by necropsy, predicting the most likely pathogen, and justifying antimicrobial use.

[Pre- and post-diagnosis body mass index in association with colorectal cancer death in a prospective cohort study].

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.

[Recommendations for the diagnosis and treatment of IgG4-related disease in China].

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition characterized by tumefactive lesions in multi-organs. It is a novel entity presented by variable manifestations. In recent years, there has been progress toward recognizing IgG4-RD. However, the diagnosis and treatment of IgG4-RD still present challenges due to insufficient experience. To address this, the Chinese Rheumatology Association has developed standardized guidelines for the diagnosis and treatment of IgG4-RD based on domestic and international experience. These guidelines aim to enhance the understanding and management of IgG4-RD, ultimately improving the prognosis for patients with IgG4-RD.