Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer–BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38–54) years and body mass index of 24·84 (22.6–28.51) kg/m² were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6–7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = −0.178, p < 0.001), poor sleep quality (r = −0.094, p < 0.05), insomnia (r = −0.098, p < 0.05), and nap frequency per week (r = −0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.     

Postoperative prognosis of pulmonary adenocarcinoma subtypes correlates with HLA-DR expression and the number of tumor-infiltrating cells

Human pulmonary adenocarcinomas (AC) can be divided into two types with special morphologic and immunohistologic properties and a different number of tumor-infiltrating cells as shown by previous investigations. In the present study the relevance of this subdivision for patients' survival was investigated. 42 surgically resected pulmonary AC of stage I and II were subclassified using light and electron microscope. For immunohistologic phenotypization, reactions with monoclonal antibodies against HLA-DR, CD1 and CD3 were studied on fresh tumor specimens. Postoperative survival was evaluated after at least 24 months. AC of type I (N=23) with mucin production and ultrastructural properties of goblet cells showed almost no HLA-DR expression. Infiltration by CD1-positive dendritic cells Langerhans cells and CD3-positive T lymphocytes was significantly lower than in AC of type II (N=19), which expressed HLA-DR homogeneously and showed, ultrastructurally, Clara cell and/or type II pneumocyte properties. Patients' outcome was similar in stage I AC of both types: about 70% of patients were still alive after 24 months. However, significant differences were found between the two types in stage II AC with regional lymph node metastases: survival of patients with AC of type II corresponded roughly with stage I tumors (67%) but only 20% of patients with type I AC were still alive after 24 months. These results indicate that postoperative prognosis for patients with pulmonary AC of type II is more favourable than for mucinous AC of type I. This may be due to the homogeneous HLA-DR expression and higher number of immunologically competent tumor-infiltrating cells which possibly results in better tumor surveillance.     

Noradrenergic innervation of peptidergic interneurons in the rat visual cortex

Previous studies have shown that cortical interneurons, presumably GABAergic, are among the targets of the noradrenaline (NA)-containing cortical afferents and that NA interacts with neuropeptides at various cellular levels. The present study attempts to characterize further the cortical targets of the NA afferents by examining, at the light and the electron microscopic level, the anatomical relationships of the NA fibers with three subpopulations of cortical interneurons, those containing somatostatin (SRIF), neuropeptide Y (NPY) or vasoactive intestinal polypeptide (VIP). For this purpose, a double preembedding immunoprocedure with antibodies against NA and SRIF, NPY or VIP was combined with the gold-substituted silver peroxidase method. Light microscopic examination showed that NA fibers contact perikarya and proximal dendrites of the SRIF, NPY and VIP neurons. However, NA fibers, while found to form pericellular arrays around NPY neurons and, to a lesser extent, around SRIF neurons, were seen to target VIP cortical cells with single terminal varicosities. Electron microscopy revealed that all peptidergic populations examined represent synaptic targets for the NA fibers. The NAergic synapses, localized onto the cell body and proximal dendrites of the peptidergic neurons, were always of the symmetrical variety. Results of the present study provide the morphological basis for the explanation of the functional interaction between the NA cortical afferent system and the intrinsic cortical elements.     

Ultrasonographic classification and phacoemulsification of white senile cataracts

OBJECTIVE: To classify the white senile cataracts and report the results of phacoemulsification of white cataracts. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: One hundred eyes were included. INTERVENTION: White cataracts were examined biomicroscopically before surgery, and their acoustic structure was analyzed with standardized A-scan echography. White cataract surgery was performed with phacoemulsification via a superior temporal near-limbus corneal approach using a bimanual divide-and-conquer or stop-and-chop technique. Patients were followed after surgery for a period of 9 months. MAIN OUTCOMES MEASURES: The A-scan acoustic structure of white cataracts; successful accomplishment of capsulorrhexis; mean phacoemulsification time, power, and energy; intraoperative and postoperative complications of phacoemulsification; and visual acuity at 9 months after surgery. RESULTS: White senile cataracts were categorized into three different types. Type I included intumescent, white cataracts with cortex liquefaction and high internal acoustic reflections (44 eyes), type II included white cataracts with voluminous nuclei, little amount of whitish solid cortex, and low internal acoustic reflections (49 eyes), and type III included white cataracts with fibrosed anterior capsule and low internal echospikes (7 eyes). Circular capsulorrhexis was completed in 79 eyes and was significantly less successful in eyes with type I intumescent, white cataracts compared with type II white cataracts (P = 0.0034). Mean phacoemulsification time and energy were higher in type II and type III white cataracts. Posterior capsule rupture occurred in ten eyes, and three of these eyes were complicated by vitreous loss. In 95 eyes, the posterior chamber lens was implanted in the capsular bag and in five eyes in the sulcus. After surgery, a transient corneal edema developed in 31 eyes. At the final 6-month examination, the mean postoperative visual acuity was 20/30. CONCLUSION: Current phacoemulsification techniques can safely manage eyes with senile white cataracts. The increased risk of difficulty with continuous capsulorrhexis in type-I and type-III white cataracts and the substantial nuclear hardness in type-II and mainly type-III white cataracts would suggest that current phacoemulsification techniques might not be as successful in these patients as they are in ordinary earlier cataracts.     

Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer.

PURPOSE: The purpose of this study was to establish the feasibility and efficacy of preoperative radiotherapy (RT) with concurrent capecitabine and oxaliplatin (XELOX-RT) in patients with rectal cancer. PATIENTS AND METHODS: Thirty-two patients with locally advanced (T3/T4) or low-lying rectal cancer received preoperative RT (total dose, 50.4 Gy). Capecitabine was administered concurrently at 825 mg/m2 bid on days 1 to 14 and 22 to 35, with oxaliplatin starting at 50 mg/m2 on days 1, 8, 22, and 29 with planned escalation steps of 10 mg/m2. End points of the phase II study included downstaging, histopathologic tumor regression, resectability of T4 disease, and sphincter preservation in patients with low-lying tumors. RESULTS: Dose-limiting grade 3 gastrointestinal toxicity was observed in two of six patients treated with 60 mg/m2 of oxaliplatin. Thus, 50 mg/m2 was the recommended dose for the phase II study. Toxicities observed at this dose level were generally mild, with only two cases of short-lived grade 3 diarrhea. Myelosuppression, mainly leukopenia, was restricted to grade 2 in 19% of patients. T-category downstaging was achieved in 17 (55%) of 31 operated patients, and 68% of patients had negative lymph nodes. Pathologic complete response was found in 19% of the resected specimens. Radical surgery with free margins could be performed in 79% of patients with T4 disease, and 36% of patients with tumors < or = 2 cm from the dentate line had sphincter-saving surgery. CONCLUSION: Preoperative XELOX-RT is a feasible and well tolerated treatment. This regimen is proposed for phase III evaluation comparing standard fluorouracil-based therapy with XELOX chemoradiotherapy.     

Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation

OBJECTIVE: To assess the effects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson's disease (PD). METHODS: The efficacy of STN stimulation on total motor disability score (unified Parkinson's disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson's disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the "off" and "on" drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the "activities of daily living" (ADL)-that is, speech, swallowing, turning in bed, falling, walking, and freezing-was obtained from each patient's questionnaire (UPDRS, part II). RESULTS: Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. CONCLUSION: These findings suggest that bilateral STN stimulation improves most axial features of Parkinson's disease and that a synergistic effect can be obtained when stimulation is used in conjunction with levodopa treatment.     

Intravascular Ultrasound for Evaluation of Left Gonadal Vein Anatomic Variations During Coil Embolization

We illustrate the intravascular ultrasound (US) findings in the evaluation of left gonadal vein anatomic variations. During a 2‐year period, 4 consecutive patients (mean age, 37 years; range, 28–45 years) with left‐sided varicocele underwent embolization. Intravascular US examinations and retrograde venography were performed to assess varicocele anatomy. Anatomic variants were recorded and categorized. A comparison between intravascular US and fluoroscopic findings was performed. The Fisher exact test was used for statistical analysis (P < .05). Technical success was achieved in all cases. There was a statistically significant difference in the maximum gonadal vein diameter between venography and intravascular US (P = .0087). Intravascular US showed left gonadal vein anatomic variations and better ability in the evaluation of the vein diameter.