Notes

Inebilizumab within AQP4-Ab-positive neuromyelitis optica array dysfunction.
This case was characterized by highly rapid cochlear destruction, and an earlier otolaryngologist consultation may have provided a more well-organized surgery plan. Pediatricians are urged to promptly consult with otolaryngologists for patients with similar indications.The genetic link between calcium signaling and RNA interference (RNAi) has remained undiscovered until now. A new study shows that wound-triggered calcium flux acts as an initial messenger for priming RNAi for its role in plant antiviral defense. This paves the way to investigate plant development and response to (a)biotic stresses.Post-translational modification of proteins with the Ubiquitin-like molecule NEDD8 is a critical regulatory mechanism for several biological processes and a potential target for therapeutic intervention. The role of NEDD8 has been mainly characterised through its modification as single moiety on the cullin family of proteins and control of Cullin-Ring-Ligases, but also on non-cullin substrates. In addition to monoNEDDylation, recent studies have now revealed that NEDD8 can also generate diverse polymers. This is either through modification of the 9 available lysines in NEDD8 and the formation of polyNEDD8 chains, or NEDDylation of Ubiquitin and SUMO-2 for the generation of hybrid NEDD8 chains. Here, we review recent findings that characterise the formation of NEDD8 polymers under distinct modes of protein NEDDylation (canonical/atypical) and their potential role as regulatory signals of the proteotoxic stress response and the Protein Quality Control system.
To report clinical outcomes and dosimetric predictors of late toxicity for patients with vaginal recurrence of endometrial cancer treated with brachytherapy in the re-irradiation setting.

On retrospective review, 32 patients with vaginal recurrence of endometrial cancer received salvage brachytherapy with or without pelvic radiotherapy (RT) from 06/2003-12/2017. Prior RT modalities were vaginal brachytherapy (19, 59%), pelvic RT (7, 22%) or both (6, 19%). Image-guided brachytherapy was performed with CT- (25, 78%) or MR-guidance (7, 22%). Vaginal control, recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan-Meier method. Late toxicity was graded by Common Toxicity Criteria for Adverse Events.

Median time from prior RT to re-irradiation was 22 months (range, 4-140). Salvage RT modalities were pelvic RT and brachytherapy (25, 78%) or brachytherapy alone (7, 22%). With median follow-up of 47 months, 3/5-year vaginal control, RFS and OS rates were 64/56%, 47/41% and 68/42%, respectively. Six patients (19%) had no evidence of disease at 85-155 months. Late grade 2/3 GI, GU and vaginal toxicity rates were 13%/16%, 19%/13%, and 9%/16%. Cumulative D2cc rectum (sum of prior and salvage RT courses) was predictive of grade 2+ and grade 3 GI toxicity. Cumulative D2cc rectum for an estimated 10% risk of late grade 2+ and 3 GI toxicity was 86 Gy and 92 Gy, respectively.

Salvage image-guided brachytherapy in the re-irradiation setting results in modest local control and increased late toxicity for localized recurrent endometrial cancer. With long-term disease control, cumulative D2cc rectum may be used to reduce late GI complication risk.
Salvage image-guided brachytherapy in the re-irradiation setting results in modest local control and increased late toxicity for localized recurrent endometrial cancer. With long-term disease control, cumulative D2cc rectum may be used to reduce late GI complication risk.
While pancreatectomy with portomesenteric venous resection and reconstruction is commonly performed for locally advanced pancreatic adenocarcinoma, little is known regarding outcomes for pancreatic neuroendocrine neoplasms (panNENs).

Patients who underwent non-parenchyma-sparing pancreatectomy for panNENs at Mayo Clinic from 2000 to 2020 were retrospectively reviewed. Propensity score matching was performed and patient characteristics and outcomes compared.

Of 867 eligible patients, 41 (4.7%) required vascular resection, including 38 patients who underwent portomesenteric venous resection only. Of these, 23 underwent pancreaticoduodenectomy or total pancreatectomy and 15 distal pancreatectomy. Patients who required portomesenteric venous resection had larger tumors, higher tumor grade, and higher disease stage. After propensity score matching to patients undergoing standard resection, the portomesenteric venous resection group had longer operative times, greater blood loss, and higher transfusion rates. While portomesenteric venous thrombosis was more common after venous resection, major complication rates and perioperative mortality were similar between the two groups, as were 5-year overall and progression-free survival.

For patients with locally advanced panNENs, pancreatectomy with portomesenteric venous resection and reconstruction can be performed in selected patients at high-volume centers with acceptable perioperative morbidity and short- and long-term survival.
For patients with locally advanced panNENs, pancreatectomy with portomesenteric venous resection and reconstruction can be performed in selected patients at high-volume centers with acceptable perioperative morbidity and short- and long-term survival.
Morbidity after pancreaticoduodenectomy (PD) has been reported to be about 30-53%. These complications can double hospital costs. We sought to explore the financial implications of complications after PD in a large institutional database.

A retrospective analysis of patients undergoing PD from 2010-2017 was performed. Costs for index hospitalization were divided into categories operating room, postoperative ward, radiology and interventional radiology. Complications were categorized according to the Clavien-Dindo classification. Univariable and mutivariable analysis were performed.

Median cost of index admission for 997 patients who underwent PD was $23,704 (range $10,988-$528,531). Patients with major complications incurred significantly greater median costs compared to those without ($40,005 vs $21,306, p<0.001). Patients with postoperative pancreatic fistula (POPF) grade A, B and C had progressively increasing costs ($32,164, $50,264 and $102,013, p<0.001). On multivariable analysis ileus/delayed gastric emptying, respiratory failure, clinically significant POPF, thromboembolic complications, reoperation, duration of surgery >240minutes and male sex were associated with significantly increased costs.

Complications after PD significantly increase hospital costs. This study identifies the major contributors towards increased cost post-PD. Initiatives that focus on prevention of complications could reduce associated costs and ease financial burden on patients and healthcare organizations.
Complications after PD significantly increase hospital costs. This study identifies the major contributors towards increased cost post-PD. Initiatives that focus on prevention of complications could reduce associated costs and ease financial burden on patients and healthcare organizations.
Pancreatic tumors are frequently diagnosed in a locally advanced stage with poor prognosis if untreated. This study assesses the safety and oncological outcomes of pancreatic surgery with arterial en-bloc resection.

We retrospectively reviewed a prospectively maintained database of patients who underwent a pancreatic resection with arterial resection between 2011 and 2020. Univariable analyses were used to assess prognostic factors for survival.

Forty consecutive patients (22 female; 18 male) undergoing arterial resections were included. Surgical procedures consisted of 19 pancreatoduodenectomies (PD, 48%), 16 distal splenopancreatectomy (DSP, 40%), and 5 total pancreatectomies (TP, 12%). Arterial resection included hepatic arteries (HA, N = 23), coeliac trunk (TC, N = 15) and superior mesenteric artery (SMA, N = 2). Neoadjuvant therapy was applied in 22 patients (58%). Major complications after surgery were observed in 15% of cases. 90-day mortality was 5%. Ceftaroline ic50 Median disease-free survival and median overall survival were for the R0/CRM- group 22.8 months and 27.9 months, 9.5 and 19.8 months for the R0/CRM+ group, and 10.1 and 13.1 months for the R1 group, respectively.

In highly selected patients, arterial en-bloc resection can be performed with acceptable mortality and morbidity rates and beneficial oncological outcome.
In highly selected patients, arterial en-bloc resection can be performed with acceptable mortality and morbidity rates and beneficial oncological outcome.Natural killer (NK) cells are innate lymphoid cells with robust antitumor functions rendering them promising therapeutic tools against malignancies. Despite constituting a minor fraction of the immune cells infiltrating tumors in the brain, insights into their role in central nervous system (CNS) pathophysiology are emerging. The challenges posed by a profoundly immunosuppressive microenvironment as well as by tumor resistance mechanisms necessitate exploring avenues to enhance the therapeutic potential of NK cells in both primary and metastatic brain malignancies. In this review, we summarize the role of NK cells in the pathogenesis of tumors in the brain and discuss the avenues investigated to harness their anticancer effects against primary and metastatic CNS tumors, including sources of therapeutic NK cells, combinations with other treatments, and novel engineering approaches for augmenting their cytotoxicity. We also highlight relevant preclinical evidence and clinical trials of NK cell-based therapies.
The objective of this systematic review was to identify and describe the psychometric properties of neonatal pain scales that were translated into Brazilian Portuguese and to verify the methodological quality of these translation, transcultural adaptations and validation.

The present study is a systematic review. A systematic search in the literature included studies of development, validation, and transcultural adaptation of neonatal pain scales to Brazilian Portuguese. The instruments must have been developed for health care professionals to evaluate neonatal pain and stress in full-term and preterm newborns.

The search strategy was conducted in PubMed, Web of Science, Scopus, and Scielo databases following The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). REVIEW /ANALYSIS METHODS A total of 1,479 publications were identified and 5 fulfilled the inclusion criteria, with 4 instruments evaluated. For the methodological quality analysis of the measurement properties of the instruments the Consensus-based Standards for Health Measurement Instruments (COSMIN) Risk of Bias checklist was used. The psychometric properties verified were internal consistency, content validity, reliability, and construct validity.

Three instruments reviewed were inadequate and one was doubtful.

The neonatal pain scales wich were cross culturally adapted to Brazilian Portuguese were shown to be of low methodological quality based on COSMIM checklist. Caution should be considered for clinical decisions about pain management judgment coming from these instruments.
The neonatal pain scales wich were cross culturally adapted to Brazilian Portuguese were shown to be of low methodological quality based on COSMIM checklist. Caution should be considered for clinical decisions about pain management judgment coming from these instruments.
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