Although diffusion-weighted imaging combined with morphologic MRI (DWIMRI) is used to detect posttreatment recurrent and second primary head and neck squamous cell carcinoma, the diagnostic criteria ...used so far have not been clarified. We hypothesized that precise MRI criteria based on signal intensity patterns on T2 and contrast-enhanced T1 complement DWI and therefore improve the diagnostic performance of DWIMRI.
We analyzed 1.5T MRI examinations of 100 consecutive patients treated with radiation therapy with or without additional surgery for head and neck squamous cell carcinoma. MRI examinations included morphologic sequences and DWI (
=0 and
=1000 s/mm
). Histology and follow-up served as the standard of reference. Two experienced readers, blinded to clinical/histologic/follow-up data, evaluated images according to clearly defined criteria for the diagnosis of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment, post-radiation therapy inflammatory edema, and late fibrosis. DWI analysis included qualitative (visual) and quantitative evaluation with an ADC threshold.
Recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment was present in 36 patients, whereas 64 patients had post-radiation therapy lesions only. The Cohen κ for differentiating tumor from post-radiation therapy lesions with MRI and qualitative DWIMRI was 0.822 and 0.881, respectively. Mean ADCmean in recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment (1.097 ± 0.295 × 10
mm
/s) was significantly lower (
< .05) than in post-radiation therapy inflammatory edema (1.754 ± 0.343 × 10
mm
/s); however, it was similar to that in late fibrosis (0.987 ± 0.264 × 10
mm
/s,
> .05). Although ADCs were similar in tumors and late fibrosis, morphologic MRI criteria facilitated distinction between the 2 conditions. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (95% CI) of DWIMRI with ADCmean < 1.22 × 10
mm
/s and precise MRI criteria were 92.1% (83.5-100.0), 95.4% (90.3-100.0), 92.1% (83.5-100.0), 95.4% (90.2-100.0), 19.9 (6.58-60.5), and 0.08 (0.03-0.24), respectively, indicating a good diagnostic performance to rule in and rule out disease.
Adding precise morphologic MRI criteria to quantitative DWI enables reproducible and accurate detection of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment.
Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein ...(VCP), key players of the protein quality control (PQC), were shown to regulate SG degradation. This is consistent with the idea that PQC may survey and/or assist SG dynamics. However, despite these observations, it is currently unknown whether the PQC actively participates in SG assembly. Here, we describe that inhibition of autophagy, lysosomes and VCP causes defective SG formation after induction. Silencing the VCP co-factors UFD1L and PLAA, which degrade defective ribosomal products (DRIPs) and 60S ribosomes, also impaired SG assembly. Intriguingly, DRIPs and 60S, which are released from disassembling polysomes and are normally excluded from SGs, were significantly retained within SGs in cells with impaired autophagy, lysosome or VCP function. Our results suggest that deregulated autophagy, lysosomal or VCP activities, which occur in several neurodegenerative (VCP-associated) diseases, may alter SG morphology and composition.
We compare abrupt CO2‐quadrupling (abrupt‐4xCO2) and ‐doubling (abrupt‐2xCO2) simulations across 10 CMIP6 models. Two models (CESM2 and MRI‐ESM2‐0) warm substantially more than twice as much under ...abrupt‐4xCO2 than abrupt‐2xCO2, which cannot be explained by the non‐logarithmic scaling of CO2 forcing. Using an energy balance model, we show that increased warming rates within these two models are driven by both less‐negative radiative feedbacks and smaller global effective heat capacity under abrupt‐4xCO2. These differences are caused by a decrease in low cloud cover and shallower ocean heat storage, respectively; both are linked to smaller fractional declines in the Atlantic Meridional Overturning Circulation (AMOC) under abrupt‐4xCO2 (relative to abrupt‐2xCO2). On a global scale, higher climate sensitivity under larger forcing can be explained by a feedback‐temperature dependence; however, we find that forcing‐dependent spatial warming patterns due to AMOC decline are an important physical mechanism which reduces warming in a way that is not captured by a global‐mean framework.
Plain Language Summary
Climate model simulations with abruptly quadrupled CO2 concentrations are often used to characterize the climate response of global climate models to greenhouse gas forcing and inform predictions of the future. In this study, we ask how relevant CO2‐quadrupling experiments are to more modest warming scenarios by comparing them to CO2‐doubling experiments. It is usually assumed that CO2‐quadrupling will produce about twice as much warming than CO2‐doubling, but this is not the case in some models. Two global climate models in particular warm much more under CO2‐quadrupling than twice the warming under CO2‐doubling. By fitting each climate model to a simpler energy balance model, we find that these two climate models are strongly impacted by the effective heat capacity (which can be impacted by ocean circulation changes) in comparison to other climate models where radiative effects (such as effects from clouds) are more impactful. Changes in the strength of an Atlantic Ocean circulation are important for both radiative effects and heat storage. Therefore, the behavior of our planet at 1.5 or 2 times CO2 cannot necessarily be estimated with quadrupling CO2 experiments.
Key Points
Models with disproportionate Atlantic Meridional Overturning Circulation (AMOC) declines under abrupt CO2 doubling experience less warming
AMOC decline modulates transient warming by influencing both low cloud feedbacks and the global effective heat capacity
Therefore, abrupt quadrupling of pre‐industrial CO2 simulations do not necessarily capture the behavior of lesser warming scenarios
Background
The natural history of sigmoid diverticulitis has been inferred from population‐based or retrospective studies. This study assessed the risk of a recurrent attack following the first ...episode of uncomplicated diverticulitis.
Methods
Patients admitted between January 2007 and December 2011 with a first episode of uncomplicated sigmoid diverticulitis confirmed on computed tomography were enrolled in this prospective study. After successful medical management of the first episode, follow‐up was conducted through yearly telephone interviews. Cox proportional hazards regression was performed to model the impact of various parameters on eventual recurrences and complications.
Results
During a median follow‐up of 24 (range 3–63) months, 46 (16·4 per cent) of 280 patients experienced a second episode of diverticulitis. Six patients (2·1 per cent) subsequently developed complicated diverticulitis and four (1·4 per cent) underwent emergency surgery for peritonitis. In multivariable analysis, a raised serum level of C‐reactive protein (over 240 mg/l) during the first attack was associated with early recurrence (hazard ratio 1·75, 95 per cent confidence interval 1·04 to 2·94; P = 0·035).
Conclusion
Uncomplicated sigmoid diverticulitis follows a benign course with few recurrences and little need for emergency surgery. Registration number: NCT01015378 (http://www.clinicaltrials.gov).
Recurrence rarely a problem
The family of the human small Heat Shock Proteins (HSPBs) consists of ten members of chaperones (HSPB1-HSPB10), characterized by a low molecular weight and capable of dimerization and oligomerization ...forming large homo- or hetero-complexes. All HSPBs possess a highly conserved centrally located α-crystallin domain and poorly conserved N- and C-terminal domains. The main feature of HSPBs is to exert cytoprotective functions by preserving proteostasis, assuring the structural maintenance of the cytoskeleton and acting in response to cellular stresses and apoptosis. HSPBs take part in cell homeostasis by acting as holdases, which is the ability to interact with a substrate preventing its aggregation. In addition, HSPBs cooperate in substrates refolding driven by other chaperones or, alternatively, promote substrate routing to degradation. Notably, while some HSPBs are ubiquitously expressed, others show peculiar tissue-specific expression. Cardiac muscle, skeletal muscle and neurons show high expression levels for a wide variety of HSPBs. Indeed, most of the mutations identified in HSPBs are associated to cardiomyopathies, myopathies, and motor neuropathies. Instead, mutations in HSPB4 and HSPB5, which are also expressed in lens, have been associated with cataract. Mutations of HSPBs family members encompass base substitutions, insertions, and deletions, resulting in single amino acid substitutions or in the generation of truncated or elongated proteins. This review will provide an updated overview of disease-related mutations in HSPBs focusing on the structural and biochemical effects of mutations and their functional consequences.
Reproduction of a given sound field interior to a circular loudspeaker array without producing an undesirable exterior sound field is an unsolved problem over a broadband of frequencies. At low ...frequencies, by implementing the Kirchhoff-Helmholtz integral using a circular discrete array of line-source loudspeakers, a sound field can be recreated within the array and produce no exterior sound field, provided that the loudspeakers have azimuthal polar responses with variable first-order responses which are a combination of a two-dimensional (2D) monopole and a radially oriented 2D dipole. This paper examines the performance of circular discrete arrays of line-source loudspeakers which also include a tangential dipole, providing general variable-directivity responses in azimuth. It is shown that at low frequencies, the tangential dipoles are not required, but that near and above the Nyquist frequency, the tangential dipoles can both improve the interior accuracy and reduce the exterior sound field. The additional dipoles extend the useful range of the array by around an octave.
Objectives
To identify imaging algorithms and indications, CT protocols, and radiation doses in polytrauma patients in Swiss trauma centres.
Methods
An online survey with multiple choice questions ...and free-text responses was sent to authorized level-I trauma centres in Switzerland.
Results
All centres responded and indicated that they have internal standardized imaging algorithms for polytrauma patients. Nine of 12 centres (75 %) perform whole-body CT (WBCT) after focused assessment with sonography for trauma (FAST) and conventional radiography; 3/12 (25 %) use WBCT for initial imaging. Indications for WBCT were similar across centres being based on trauma mechanisms, vital signs, and presence of multiple injuries. Seven of 12 centres (58 %) perform an arterial and venous phase of the abdomen in split-bolus technique. Six of 12 centres (50 %) use multiphase protocols of the head (n = 3) and abdomen (n = 4), whereas 6/12 (50 %) use single-phase protocols for WBCT. Arm position was on the patient`s body during scanning (3/12, 25 %), alongside the body (2/12, 17 %), above the head (2/12, 17 %), or was changed during scanning (5/12, 42 %). Radiation doses showed large variations across centres ranging from 1268-3988 mGy*cm (DLP) per WBCT.
Conclusions
Imaging algorithms in polytrauma patients are standardized within, but vary across Swiss trauma centres, similar to the individual WBCT protocols, resulting in large variations in associated radiation doses.
Key Points
•
Swiss trauma centres have internal standardized imaging algorithms for trauma patients
•
Whole-body CT is most commonly used for imaging of trauma patients
•
CT protocols and radiation doses vary greatly across Swiss trauma centres
CT-scan-guided percutaneous abscess drainage of Hinchey Stage II diverticulitis is considered the best initial approach to treat conservatively the abscess and to subsequently perform an elective ...sigmoidectomy. However, drainage is not always technically feasible, may expose the patient to additional morbidity, and has not been critically evaluated in this indication. This study was undertaken to compare the results of percutaneous drainage vs. antibiotic therapy alone in patients with Hinchey II diverticulitis.
This was a case-control study of all patients who presented in our institution with Hinchey Stage II diverticulitis between 1993 and 2005. Thirty-four patients underwent abscess drainage under CT-scan guidance (Group 1), and 32 patients were treated with antibiotic therapy alone (Group 2), in most cases because CT-scan-guided abscess drainage was considered technically unfeasible by the interventional radiology team. Initial conservative treatment was considered a failure when: 1) emergency surgery had to be performed, 2) signs of worsening sepsis developed, and 3) abscess recurred within four weeks of drainage.
The median size of abscess was 6 (range, 3-18) cm in Group 1 and 4 (range, 3-10) cm in Group 2 (P = 0.002). Median duration of drainage was 8 (range, 1-18) days. Conservative treatment failed in 11 patients (33 percent) of Group 1, and in 6 patients (19 percent) of Group 2 (P = 0.26). Ten patients (29 percent) in Group 1 and five patients (16 percent) in Group 2 underwent emergency surgery (P = 0.24); there were four postoperative deaths (26.6 percent) in this subgroup. Twelve patients (35 percent) in Group 1 and 16 patients (50 percent) in Group 2 subsequently underwent an elective sigmoid resection (P = 0.31). In this subgroup of patients, there was neither anastomotic leakage nor postoperative death.
Emergency surgery for Hinchey Stage II diverticulitis carries a high mortality rate and should be avoided. To achieve this, antibiotic therapy alone seems to be a safe alternative, whenever percutaneous drainage is technically difficult or hazardous. Actually, our data did not demonstrate any benefit of CT scan-guided percutaneous abscess drainage, suggesting that the role of interventional radiology techniques in this indication deserves further critical evaluation.
Aberrations on TP53, either as deletions of chromosome 17p (del17p) or mutations, are associated with poor outcome in multiple myeloma (MM), but conventional detection methods currently in use ...underestimate their incidence, hindering an optimal risk assessment and prognostication of MM patients. We have investigated the altered status of TP53 gene by SNPs array and sequencing techniques in a homogenous cohort of 143 newly diagnosed MM patients, evaluated both at diagnosis and at first relapse: single-hit on TP53 gene, either deletion or mutation, detected both at clonal and sub-clonal level, had a minor effect on outcomes. Conversely, the coexistence of both TP53 deletion and mutation, which defined the so-called double-hit patients, was associated with the worst clinical outcome (PFS: HR 3.34 95% CI: 1.37-8.12 p = 0.008; OS: HR 3.47 95% CI: 1.18-10.24 p = 0.02). Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients.
PDF
