Influence of lymph node degeneration on metastases in prostate cancer: or why we must look for a needle in a haystack.

BACKGROUND: To evaluate the incidence of lymph node degeneration and its association with nodal metastatic pattern in prostate cancer. METHODS: A retrospective analysis of the submitted lymph node specimen of 390 prostatectomies in 2011 was performed. All lymph nodes were histologically re-evaluated and the degree of lymph node degeneration e.g. lipomatous atrophy, capsular and framework fibrosis, and calcifications as well as the lymph node size were recorded. Lymph node degeneration was compared in the anatomic regions of the pelvis as well as in lymph nodes with and without metastases of prostatic cancer. RESULTS: Eighty-one of 6026 lymph nodes demonstrated metastases. Complete histologic examination with analysis of a complete cross-section was possible in 5173 lymph nodes including all lymph nodes with metastases. The incidence of lymph node degeneration was different across the various landing sites. Lymph node metastases were primarily detected in less degenerative and therefore more functional lymph nodes. In metastatic versus non-metastatic lymph nodes low lipomatous atrophy was reported in 84.0% versus 66.7% (p = 0.004), capsular fibrosis in 14.8% versus 35.4% (p < 0.001), calcifications in 35.8% versus 46.1% (p = 0.072) and framework fibrosis in 69.8% versus 75.3% (p = 0.53). Metastases were also identified more frequently in larger than in smaller lymph nodes (63.0% vs. 47.5%; p = 0.007). CONCLUSIONS: Degenerative changes in pelvic lymph nodes are commonly detectable but occur with variable frequency in the various nodal landing sites in the pelvis. The degree of lymph node degeneration of single lymph nodes has a significant influence on whether a lymph node is infiltrated by tumor cells and may harbour metastases.

CSF shunt valve occlusion-does CSF protein and cell count matter?

BACKGROUND: Shunt obstruction is a common cause of shunt failure in the treatment of hydrocephalus. Valve occlusion is traditionally believed to originate from elevated CSF protein or cellular components, although detailed evidence is scarce and contradictory. Therefore, this study aimed to examine CSF protein and cell count as risk factors for valve obstruction. METHODS: We retrospectively examined 274 patients who underwent shunt placement for hydrocephalus between 2009 and 2018 and had at least 1 year follow-up. Age, aetiology of hydrocephalus, valve type, occurrence of revision, reason for revision and CSF protein and cell count at the time of shunt insertion and revision surgery were analysed. RESULTS: Thirty-two of 274 patients (11.7%) required revision surgery due to valve occlusion. Mean time to revision was 143 days. CSF white blood cell (WBC) count but not protein was associated with valve occlusion overall. Of all obstructed valve patients, 25% showed CSF protein level within the normal range, whereas 13.6% of the patients overall showed greatly elevated CSF protein level without evidence of valve obstruction. Persistently elevated CSF protein level at the time of shunt revision was significantly associated with valve obstruction within 90 days of initial insertion (early occlusion). Children with congenital malformations and post-haemorrhagic patients were significantly overrepresented in the occlusion group, particularly in the early occlusion group. CONCLUSION: Pathological CSF values such as WBC count and persistently elevated protein level serves as a risk factor for early valve obstruction. Late obstruction occurs independent of normal CSF values. Infants are particularly prone to early and late valve obstructions. CSF protein level at shunt insertion is not predictive of valve occlusion.

Treatment for secondary deterioration in idiopathic normal pressure hydrocephalus in the later course of the disease: a retrospective analysis.

BACKGROUND: Cerebrospinal fluid (CSF) shunting is a highly effective treatment for idiopathic normal pressure hydrocephalus (iNPH). However, secondary deterioration can occur at a later time. Thus, the current study aimed to evaluate the incidence rate and causes of secondary deterioration. METHODS: A retrospective analysis was conducted on all patients with iNPH who were treated with implantation of a CSF shunt since 1993. A meticulous shunt workup was recommended to all patients who presented to our department with secondary deterioration during their follow-up visits. Data about the proportion of patients with such deterioration and its causes, subsequent treatment, and clinical outcome were obtained. RESULTS: A total of 169 patients were included, and the mean follow-up time was 69.2 months. In total, 119 (70.4%) patients presented with a total of 153 secondary deteriorations. In 9 cases (5.9%), the deterioration was caused by delayed subdural hematoma and in 27 (22.1%) cases, by shunt dysfunction. Invasive shunt testing was commonly required to validate shunt failure. Moreover, 19 of 27 patients experienced a satisfactory improvement after revision surgery. In total, 86 deteriorations were attributed to nonsurgical causes, and the valve pressure was decreased in 79 patients, with only 16.5% presenting with a satisfactory improvement after lowering of valve pressure. CONCLUSIONS: Most patients with shunted iNPH presented with deterioration in the later course of the disease. Shunt dysfunction was considered a cause of secondary deterioration. Moreover, shunt revision surgery was a highly effective treatment, and patients with deterioration should undergo screening procedures for shunt dysfunction, including invasive shunt testing.

Delayed modulation of alpha band activity increases response inhibition deficits in adolescents with AD(H)D.

Deficiencies in inhibitory control are one of the hallmarks of attention-deficit-(hyperactivity) disorder (AD(H)D). Response inhibition demands can become increased through additional conflicts, namely when already integrated representations of perception-action associations have to be updated. Yet, the neural mechanisms of how such conflicts worsen response inhibition in AD(H)D are unknown, but, if identified, could help to better understand the complex nature of AD(H)D-associated impulsivity. We investigated both behavioral performance and EEG activity in the theta and alpha band of adolescents (10-18 years of age) with AD(H)D (n = 28) compared to neurotypical (NT) controls (n = 33) in a conflict-modulated Go/Nogo paradigm. We used multivariate pattern analysis (MVPA) and EEG-beamforming to examine how changes in representational content are coded by oscillatory activity and to delineate the cortical structures involved in it. The presented behavioral and neurophysiological data show that adolescents with AD(H)D are more strongly affected by increased response inhibition demands through additional conflicts than NT controls. Precisely, AD(H)D participants showed higher false alarm rates than NT controls in both, non-overlapping and overlapping Nogo trials, but performed even worse in the latter. This is likely due to an inefficient updating of representations related to delayed modulations of alpha band activity in the ventral stream and orbitofrontal regions. Theta band activity is also modulated by conflict but was not differentially affected in the two groups. By this, the present study provides novel insights into underlying neurophysiological mechanisms of the complex nature of response inhibition deficits in adolescents with AD(H)D, stressing the importance to examine the interplay of theta and alpha band activity more closely to better understand inhibitory control deficits in AD(H)D.

Preserved perception-action integration in adolescents after a COVID-19 infection.

Evidence is accumulating that the Coronavirus disease (COVID-19) can bring forth deficits in executive functioning via alterations in the dopaminergic system. Importantly, dopaminergic pathways have been shown to modulate how actions and perceptions are integrated within the brain. Such alterations in event file binding could thus underlie the cognitive deficits developing after a COVID-19 infection. We examined action-perception integration in a group of young people (11-19 years of age) that had been infected with COVID-19 before study participation (n = 34) and compared them to a group of uninfected healthy controls (n = 29) on the behavioral (i.e., task accuracy, reaction time) and neurophysiological (EEG) level using an established event file binding paradigm. Groups did not differ from each other regarding demographic variables or in reporting psychiatric symptoms. Overall, multiple lines of evidence (behavioral and neurophysiological) suggest that action-perception integration is preserved in adolescents who suffered from COVID-19 prior to study participation. Event file binding processes were intact in both groups on all levels. While cognitive impairments can occur following a COVID-19 infection, the study demonstrates that action-perception integration as one of the basic building blocks of cognition seems to be largely unaffected in adolescents with a rather mild course of the disease.

Impact of timing and combination of different BNT162b2 and ChAdOx1-S COVID-19 basic and booster vaccinations on humoral immunogenicity and reactogenicity in adults.

In this single-center observational study with 1,206 participants, we prospectively evaluated SARS-CoV-2-antibodies (anti-S RBD) and vaccine-related adverse drug reactions (ADR) after basic and booster immunization with BNT162b2- and ChAdOx1-S-vaccines in four vaccination protocols: Homologous BNT162b2-schedule with second vaccination at either three or six weeks, homologous ChAdOx1-S-vaccination or heterologous ChAdOx1-S/BNT162b2-schedule, each at 12 weeks. All participants received a BNT162b2 booster. Blood samples for anti-S RBD analysis were obtained multiple times over a period of four weeks to six months after basic vaccination, immediately before, and up to three months after booster vaccination. After basic vaccination, the homologous ChAdOx1-S-group showed the lowest anti-S RBD levels over six months, while the heterologous BNT162b2-ChAdOx1-S-group demonstrated the highest anti-S levels, but failed to reach level of significance compared with the homologous BNT162b2-groups. Antibody levels were higher after an extended vaccination interval with BNT162b2. A BNT162b2 booster increased anti-S-levels 11- to 91-fold in all groups, with the homologous ChAdOx1-S-cohort demonstrated the highest increase in antibody levels. No severe or serious ADR were observed. The findings suggest that a heterologous vaccination schedule or prolonged vaccination interval induces robust humoral immunogenicity with good tolerability. Extending the time to boost-immunization is key to both improving antibody induction and reducing ADR rate.

Degenerative Changes in Aging Human Pelvic Lymph Nodes-A Reason to Rethink Staging and Therapy of Regional Malignancies?

Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence and extent. A total of 5173 pelvic lymph nodes of 390 patients aged 44 to 79 years (median 68 years, IQR 62-71 years) were histologically examined for degenerative structural changes. Lymph node size, lipomatous atrophy, capsular fibrosis, framework fibrosis, and calcifications were recorded semi-quantitatively and evaluated by age group. Significantly more lymph nodes <10 mm were found in older patients (p = 0.001). The incidence of framework fibrosis, capsular fibrosis, and calcifications increased significantly with increasing patient age (p < 0.001). In lipomatous atrophy, an increase in mild to moderate lipomatous atrophy was observed with increasing age (p < 0.001). In this, the largest study to date on this topic, age-related degenerative changes in pelvic lymph nodes were proven. Due to the consecutive decrease in hte filtration function of pelvic lymph nodes with increasing age, staging and therapy of metastatic pelvic urologic carcinomas should be reconsidered.

A prospective randomized study comparing retractor-endoscopic vs. open release of carpal tunnel and cubital tunnel syndromes.

OBJECTIVE: To evaluate the neurological and neurophysiological outcomes of retractor-endoscopic versus open release in carpal tunnel syndrome (rCTS and oCTS, respectively) and cubital tunnel syndrome (rCbTS and oCbTS, respectively) at 3- and 12-month follow-up. METHODS: Between 2013 and 2017, 80 patients were prospectively blindly randomized. McGowan scores were used for preoperative grading and outcomes were assessed using a modified Bishop rating system (BRS). Furthermore, incapacity to work, duration of postoperative pain, hypoesthesia, atrophy, subjective weakness, and a subjective assessment of the operative result were analyzed. The differences in the cohorts were evaluated with t-tests and ANOVAs as parametric tests and Kruskal-Wallis and Mann-Whitney U tests as nonparametric tests. RESULTS: The 80 patients underwent retractor-endoscopic or open decompression of the median or ulnar nerve. The rCTS group exhibited significant improvements in neurophysiological data (P = 0.032), shorter periods of postoperative pain (P = 0.03), and less discomfort (P = 0.005), as well as significantly better BRS results after 3 months compared with the oCTS group (P = 0.005). Between the oCbS and rCbTS groups, no significant differences were observed (P > 0.05). Regarding improvements in McGowan scores, no statistically significant differences were observed between the rCTS and oCTS groups after 3 months (P = 0.52) or 12 months (P = 0.86), nor were any observed between the rCbTS and oCbTS groups after 3 months (P = 0.88) or 12 months (P = 0.10). CONCLUSION: Significantly superior results were obtained at short-term follow-up for rCTS, whereas no superiority was found for rCbTS release. This study concluded that this endoscopic procedure is safe as well as and effective and has the potential to achieve better results in carpal tunnel syndrome compared with conventional methods.

[3,3]-Sigmatropic rearrangement step in the gold-catalyzed cyclization of allyl-(ortho-alkinylphenyl)methyl ethers.

The gold-catalyzed conversion of allyl-(ortho-alkynylphenyl)methyl ethers was investigated, and allylated isochromenes were obtained. An optimization of the catalysis conditions with respect to different phosphane and carbene ligands on gold, different counterions, and different solvents was conducted. Subsequently, the scope and limitations of this reaction were investigated with 21 substrates. The mechanistic studies show an allylic inversion, as supported by NMR data and an X-ray crystal structure analysis, as well as an intermolecular reaction, as determined by crossover experiments. There is no competition of protodeauration even in the presence of water. All these observations differ from other related conversions and clearly indicate product formation by a [3,3]sigmatropic rearrangement in the step forming the new C-C bond.