Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.

Multi-stage freezing of HEUR polymer networks with magnetite nanoparticles.

We observe a change in the segmental dynamics of hydrogels based on hydrophobically modified ethoxylated urethanes (HEUR) when hydrophobic magnetite nanoparticles (MNPs) are embedded in the hydrogels. The dynamics of the nanocomposite hydrogels is investigated using dielectric relaxation spectroscopy (DRS) and neutron spin echo (NSE) spectroscopy. The magnetic nanoparticles within the hydrophobic domains of the HEUR polymer network increase the size of these domains and their distance. The size increase leads to a dilution of the polymers close to the hydrophobic domain, allowing higher mobility of the smallest polymer blobs close to the "center". This is reflected in the decrease of the activation energy of the ß-process detected in the DRS data. The increase in distance leads to an increase of the size of the largest hydrophilic polymer blobs. Therefore, the segmental dynamics of the largest blobs is slowed down. At short time scales, i.e. 10(-9) s < τ < 10(-3) s, the suppression of the segmental dynamics is reflected in the α-relaxation processes detected in the DRS data and in the decrease of the relaxation rate Γ of the segmental motion in the NSE data with increasing concentration of magnetic nanoparticles. The stepwise (multi-stage) freezing of the small blobs is only visible for the pure hydrogel at low temperatures. On the other hand, the glass transition temperature (Tg) decreases upon increasing the MNP loading, indicating an acceleration of the segmental dynamics at long time scales (τ∼ 100 s). Therefore, it would be possible to tune the Tg of the hydrogels by varying the MNP concentration. The contribution of the static inhomogeneities to the total scattering function Sst(q) is extracted from the NSE data, revealing a more ordered gel structure than the one giving rise to the total scattering function S(q), with a relaxed correlation length ξNSE = (43 ± 5) Å which is larger than the fluctuating correlation length from a static investigation ξSANS = (17.2 ± 0.3) Å.

Individualized quality of life of severely affected multiple sclerosis patients: practicability and value in comparison with standard inventories.

PURPOSE: Individualized quality of life (QoL) measures differ from traditional inventories in that QoL domains/weights are not predetermined, but identified by the individual. We assessed practicability of the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW) interview in severely affected multiple sclerosis (MS) patients; the key QoL dimensions identified; and the correlation of the SEIQoL-DW index score with standard patient-reported outcome measures (PROMs). METHODS: Participants were people with severe MS who performed the baseline visit of the PeNSAMI trial (ISRCTN73082124). The SEIQoL-DW was administered at the patient's home by a trained examiner. Patients then received the following PROMs: the Core-Palliative care Outcome Scale (Core-POS), the Palliative care Outcome Scale-Symptoms-MS (POS-S-MS), the European Quality of Life Five Dimensions-3L (EQ-5D-3L), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Of 59 enrolled patients, 11 (19 %) did not receive the SEIQoL-DW (and the other PROMs) because of severe cognitive compromise or inability to communicate. SEIQoL-DW administration was completed and deemed valid in all 48 cases (mean age 60 years, 58 % women, median Expanded Disability Status Scale score 8.5). Mean SEIQoL-DW index score was 59.1 (SD 25.5). The most commonly nominated SEIQoL-DW areas were family (94 % of the patients), relationships, and leisure activities (both 65 %). Core-POS and POS-S-MS contained 70 % of the SEIQoL-DW-nominated areas. Nevertheless, correlations between SEIQoL-DW index, Core-POS, and POS-S-MS (and the other PROMs) were negligible. CONCLUSIONS: Individualized QoL can be assessed in severely affected MS patients, providing information that is not tracked by the standard inventories Core-POS, POS-S-MS, EQ-5D-3L, and HADS.

Computed tomographic features of urinary bladder torsion in two dogs.

Urinary bladder torsion is rare in dogs. It is characterised by rotation of the organ along its longitudinal axis and is potentially life-threatening because of urinary flow obstruction with subsequent urine retention, hydroureter, hydronephrosis and azotaemia. This report describes the computed tomographic features of urinary bladder torsion in two dogs. In both cases, the hallmark indicative of torsion was the "whirl sign," originating from the twisted pelvic urethra and urinary bladder neck encircling the ureters, blood vessels and bladder ligaments in a characteristic spiral pattern. The imaging features correlated well with surgical findings, demonstrating high sensitivity of computed tomography in the preoperative diagnosis of urinary bladder torsion.

Potato Consumption Is not Associated with Higher Risk of Mortality: A Longitudinal Study among Southern Italian Older Adults.

OBJECTIVE: The consumption of potatoes is increasing worldwide, but few studies have assessed the association between potato consumption and mortality, particularly in Mediterranean countries. We therefore investigated whether potato consumption is associated with higher risk of death in a large cohort of people living in South Italy. DESIGN: Longitudinal. SETTING: Community-dwelling. MEASUREMENTS: 2,442 participants coming from MICOL and NUTRIHEP studies aged more than 50 years at baseline were followed-up for 11 years. Dietary intake was assessed by means of a Food Frequency Questionnaire. Potato consumption was categorized in quintiles according to their daily consumption (< 3.95, 3.96-8.55, 8.56-15.67, 15.68-22.0, and > 22.0 g/day). Mortality was ascertained through validated cases of death. The association between potato consumption and mortality was assessed through Cox's regression models, adjusted for potential confounders, and reporting the data as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The 2,442 eligible participants were prevalently males (54.6%) and aged a mean of 64.3±9.3 years. During the 11-year follow-up, 396 (=16.2%) participants died. After adjusting for 12 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not have an increased overall mortality risk (HR=0.75; 95%CI: 0.53-1.07). Modelling the potato consumption as continuous (i.e. as increase in 10 g/day) did not substantially change our findings (fully-adjusted HR=0.93; 95%CI: 0.84-1.02). CONCLUSION: Overall potato consumption was not associated with higher risk of death in older people living in a Mediterranean area. Future studies are warranted to elucidate the role of potato consumption on all-cause and cause-specific mortality.

Expression of Bcl-2, p53, c-jun and c-fos protooncogenes in keloids and hypertrophic scars.

Keloids and hypertrophic scars represent a model of altered wound healing characterized by overproduction of extracellular matrix and dermal fibroblasts with high mitotic rate. Alteration of apoptosis and cell proliferation has been implicated in the etiology of keloids. The bcl-2 protooncogene encodes a protein that protects cells from programmed cell death while p53 protein functions as negative regulator of cell proliferation. Both protooncogenes have been shown to play a role in tissue homeostasis as apoptotic regulatory genes. The c-jun and c-fos protooncogenes are transactivating factors also involved in fibroblast proliferation. In our study we investigated, by immunohistochemistry, skin specimens from three clinically active hypertrophic scars and keloids, two resting keloids and two early phase morphea to detect both bcl-2 and p53 protein expression, in order to evaluate these apoptotic regulatory genes in different fibrotic conditions. The c-jun and c-fos, at protein and mRNA level, and Ki67 nuclear antigen expression were also investigated. In hypertrophic scars and active keloids we could detect intense Bcl-2 staining in basal keratinocytes and in scattered fibroblast-like and perivascular spindle-shaped cells, while no p53 expression could be demonstrated. The c-jun and c-fos mRNA and protein expression was mainly found in dermal fibroblast-like cells and elongated perivascular cells in all skin biopsies, and similar immunostaining pattern was observed for Ki67 antigen. No protooncogene expression in morphea patients and normal skin, unless Bcl-2 staining in the basal layer of normal epidermis, was documented. Our results suggest that Bcl-2, c-jun and c-fos protein expression and lack of p53 detection in fibroblast-like and perivascular spindle cells are related to increased fibroblast proliferation, confirmed by Ki67 positivity, probably due to alteration of these regulatory apoptotic genes resulting in pathological scarring.

[Contribution to studies on the treatment of cancer of the prostate with D-Trp6-LH-RH]. / Contribution aux études sur le traitement du cancer de la prostate par le D-Trp6-LH-RH.

The authors review 55 cases of adenocarcinoma of the prostate, from July 1982 to June 1983. The mean age of these patients was 61.5 years. None of them underwent orchiectomy. They were all treated with an LH-RH analogue: Decapeptyl. In 74.5% of the patients a consistent decrease of tumour mass in the prostate to about half its original size was observed, in association with a shrinking of the metastases. The Karnofsky index improved in 89% of the patients. The authors believe that Decapeptyl is preferable to surgical castration because it allows an improvement in pain symptoms, a regression of the primary tumour and metastases and achieves a better balance of serum levels of testosterone, FSH and LH.

Nipple reconstruction by local flaps: a long-term comparative study between star and skate techniques.

Nipple reconstruction often gives the highest satisfaction to the patient despite being just a minor procedure. During the last 50 years, many techniques have been described in order to improve the cosmetic appearance. Star and skate flaps are two of the most frequently reported procedures. The aim of this study was to compare the personal experience of two plastic surgery departments that have been using these two different methods. Thirty patients have been included in this study. Nipple projection and cosmetic appearance have been evaluated by both patients and surgeons. Follow-up ranged between 1 and 5 years. Results have been compared. Both techniques proved to be versatile and valid. The skate flap seemed to keep projection for a longer time, while the star technique gave a better cosmetic appearance.

Two-stage treatment of a secondary aortoesophageal fistula after thoracic endovascular aneurysm repair.

Secondary aortoesophageal fistula is a relatively rare but very often lethal complication that may develop after thoracic endovascular aneurysm repair (TEVAR). The clinical syndrome is well explained by the Chiari triad: midthoracic pain and/or dysphagia, and sentinel minor hematemesis followed by massive hematemesis. The incidence of this serious complication has increased with the growing number of patients undergoing TEVAR. This case report describes a patient who was seen in the emergency department at this hospital because of fever, sepsis and thoracic pain radiating to the back and unresponsive to drug therapy, diagnosed with a secondary aortoesophageal fistula and subsequently treated with a two stage surgical procedure.

Allergy and multiple sclerosis: a population-based case-control study.

BACKGROUND: Epidemiological studies on the association between allergic disorders, T-helper type 2 (Th2) mediated, and multiple sclerosis (MS), a T-helper type 1 (Th1)/Th17-mediated disease, provided conflicting results. OBJECTIVE: The aim of this study was to further examine the association between allergic disorders and MS. METHODS: The association between MS and previous medical history of any type of allergy has been investigated in a population-based case-control study conducted in Northern Italy, based on telephone interviews to 423 cases and 643 population controls (refusal rates 3.7% and 9.4%, respectively). Controls were a random sample of the general population. RESULTS: A history of atopic allergies seems to confer protection against MS (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.38-0.89; P = 0.012). In particular, the prevalence of allergic asthma was 4.9% in people with MS and 12% in control subjects (OR = 0.38; 95% CI 0.22-0.66, P < 0.01). No association was found between MS and nonatopic allergies. CONCLUSIONS: Our findings are confirmatory of the putative protective effect of Th2-mediated disorders on Th1 immune responses associated with MS. A unifying theory on the mechanisms by which previous history of atopic allergies may modify the risk of MS is still lacking.

A new mutation (G51C) in the iron-responsive element (IRE) of L-ferritin associated with hyperferritinaemia-cataract syndrome decreases the binding affinity of the mutated IRE for iron-regulatory proteins.

Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.

Coexistence of haemophilia A and von Willebrand's disease in the same kindred.

A clinical and laboratory investigation of a kindred in which haemophilia A and autosomal recessive von Willebrand's disease (VWD) were concomitantly present is described. 3 male patients were shown to be hemizygotes for moderate haemophilia A, one female appeared to be haemophilia A carrier and 3 males showed laboratory findings consistent with heterozygosity for autosomal recessive VWD. In one woman, the pedigree and laboratory findings suggest the possibility of double heterozygosity.

Motor evoked potentials in the post-surgical follow-up of cervical spondylotic myelopathy.

Eighteen patients (6 female, 12 male; average age 51 years, range 37-79) with clinical and radiological evidence (MRI) of cervical spondylotic myelopathy (CSM) were examined. The subjects were divided into two groups depending on whether radiology indicated single level (9 patients) or multilevel (9 patients) compression of the cervical cord. All of the patients underwent surgical decompression. Seriate exam with trans-cranial magnetic stimulation was performed in double session before surgery, and 3 and 12 months after surgery. The follow-up study of these patients revealed a statistically significant neurophysiological improvement only in those patients with single-level compression. In these cases, the cervical cord pathology revealed by MRI signal hyperintensity in T2 may at least partially consist of an edematous component and/or an initial demyelinization that has still a chance of recovery. In patients with multilevel damage, the compression may cause irreversible lesions.