Psychological factors and long-term tinnitus handicap in vestibular schwannoma patients after retrosigmoid microsurgery - a cross-sectional study.

OBJECTIVE: This study aimed to investigate the connection between psychological factors and postoperative tinnitus in vestibular schwannoma (VS) patients following retrosigmoid microsurgery. DESIGN: Cross-sectional study. STUDY SAMPLE: Ninety-three VS patients participated, completing questionnaires on demographics, tinnitus severity (THI-12), personality traits (TIPI-G), dizziness impact (DHI), perceived health benefits (GBI), somatisation tendencies (SOMS-2), and psychological distress (HADS-D). Our analysis involved Mann-Whitney U-tests, Spearman's rank-order correlations, and false discovery rate correction. RESULTS: Most participants reported postoperative tinnitus (77/93), with 41 experiencing it preoperatively. Emotional stability correlated negatively with tinnitus presence, while tinnitus severity was associated with emotional distress. Preoperative somatisation tendencies were also positively linked to tinnitus severity. Postoperative Tinnitus was further linked to reduced perceived health benefits and increased anxiety and depression levels. Notably, age and gender showed no significant associations. CONCLUSION: This study uncovers the interplay between postoperative tinnitus and psychological factors in VS patients, highlighting emotional and cognitive dimensions. Tailored psychological interventions addressing tinnitus's psychosomatic impact may enhance patients quality of life.

Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion.

BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).

Rapid, complete and sustained tumour response to the TRK inhibitor larotrectinib in an infant with recurrent, chemotherapy-refractory infantile fibrosarcoma carrying the characteristic ETV6-NTRK3 gene fusion.

BACKGROUND: The ETV6-NTRK3 gene fusion is present in the majority of cases of infantile fibrosarcoma (IFS) and acts as a potent oncogenic driver. We report the very rapid, complete, and sustained response of an advanced, chemotherapy-refractory, recurrent IFS to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib. PATIENT AND METHODS: A male infant born with a large congenital IFS of the tongue had the tumour surgically resected at age 4 days. Within 2 months, he developed extensive lymph node recurrence that progressed during two cycles of vincristine-doxorubicin-cyclophosphamide chemotherapy. At screening, a large right cervical mass was clinically visible. Magnetic resonance imaging (MRI) revealed bilateral cervical and axillary lymph node involvement as well as infiltration of the floor of the mouth. The largest lesion measured 5.5×4.5×4.4 cm (ca. 55 cm3). The patient started outpatient oral larotrectinib at 20 mg/kg twice daily at age 3.5 months. RESULTS: After 4 days on treatment, the parents noted that the index tumour was visibly smaller and softer. The rapid tumour regression continued over the following weeks. On day 56 of treatment, the first scheduled control MRI showed the target lesion had shrunk to 1.2×1.2×0.8 cm (ca. 0.6 cm3), corresponding to a complete response according to the Response Evaluation Criteria In Solid Tumors version 1.1. This response was maintained over subsequent follow-up visits, and on day 112 at the second control MRI the target lymph node was completely normal. At last follow-up, the disease remained in complete remission after 16 months on larotrectinib, with negligible toxicity and no safety concerns. CONCLUSION(S): Selective TRK inhibition by larotrectinib offers a novel, highly specific and highly effective therapeutic option for IFS carrying the characteristic ETV6-NTRK3 gene fusion. Its use should be considered when surgery is not feasible. (NCT02637687).

[Neurofeedback in the Treatment of Anorexia Nervosa: a Case Report]. / Der Einsatz von Neurofeedback bei Anorexia nervosa: ein Fallbeispiel.

Anorexia nervosa has been related to alterations in brain activity in terms of hyperactive EEG patterns. This case report illustrates the principles and results of a five-week neurofeedback treatment in a 29-year-old woman suffering from anorexia nervosa. A neurofeedback protocol to enhance alpha activity (8 - 12 Hz) was developed and conducted additionally to the standardized treatment for eating disorders in training sessions twice a week. Pre- and post-test measurements included resting state EEG measurements and a psychological test battery. The results show improvements from pre- to post-test in eating disorder psychopathology including psychological wellbeing, emotional competence, and eating behavior traits. In addition, a decrease in theta power (4 - 7 Hz), a well-known trait marker of anorexia nervosa, was measured. However, our data should be interpreted with caution because this is a single case study. Nevertheless, this report documents the practicability and method of neurofeedback as treatment adjunct in eating disorders from the clinical perspective. Although the use of neurofeedback in the treatment of anorexia nervosa is recommended in literature, empirical studies are still lacking. Randomized controlled trials to evaluate short- and long-term effects of neurofeedback are needed.

Probing Charges on the Atomic Scale by Means of Atomic Force Microscopy.

Kelvin probe force spectroscopy was used to characterize the charge distribution of individual molecules with polar bonds. Whereas this technique represents the charge distribution with moderate resolution for large tip-molecule separations, it fails for short distances. Here, we introduce a novel local force spectroscopy technique which allows one to better disentangle electrostatic from other contributions in the force signal. It enables one to obtain charge-related maps at even closer tip-sample distances, where the lateral resolution is further enhanced. This enhanced resolution allows one to resolve contrast variations along individual polar bonds.

Production of inflammatory mediators and extracellular traps by carp macrophages and neutrophils in response to lipopolysaccharide and/or interferon-γ2.

Neutrophilic granulocytes and macrophages are crucial for the innate immune response against infections. They migrate into the focus of inflammation, where they efficiently bind, engulf and kill bacteria by proteolytic enzymes, antimicrobial peptides, reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, activated neutrophils and macrophages can form extracellular traps (ETs). Fish neutrophils and macrophages are morphologically, histochemically, and functionally similar to their mammalian counterparts, but their significance for regulation of inflammatory responses and pathogen killing needs further elucidation. We compared the activity of head kidney monocytes/macrophages and neutrophilic granulocytes of common carp and established that upon lipopolysaccharide stimulation, not only neutrophils, but also carp monocytes/macrophages release extracellular DNA and are capable to form macrophage extracellular traps (METs). To clarify whether many specific LPS functions reported for piscine phagocytes might be due to impurities in the commonly used LPS preparations we studied expression of inflammatory mediators, release of DNA, ROS and RNS in cells stimulated with LPS or its highly purified form (pLPS). Also IFN-γ2 stimulation and its synergism with LPS/pLPS in stimulating expression of pro-inflammatory mediators was studied. Results substantiate that a classical stimulation of TLR4 by LPS may indeed be absent in carp as most of the classically reported LPS effects are abolished or diminished when pLPS is used. Interestingly, we also observed a potent IL-10 expression in neutrophilic granulocytes upon LPS stimulation, which, apart from their pro-inflammatory function, clearly indicates a role in restrictive control of the inflammatory reaction.

Histopathological assessment of tumour regression, nodal stage and status of resection margins determines prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy.

OBJECTIVES: In advanced oral squamous cell carcinoma (OSCC), tumour regression after neoadjuvant radiochemotherapy seems to be an important prognostic factor. In this study, we intended to compare regression grading according to two previously described regression models and to analyse the association of tumour regression and other tumour characteristics with patients' characteristics and overall survival. METHODS: The retrospective study included 63 treatment-naive patients with primary OSCC of stages II-IV, who were treated with a concomitant neoadjuvant radiochemotherapy followed by radical surgery. Assessment of histopathological features was performed, there under regression grading according to two previously described regression models. RESULTS: Both tumour regression models provided comparable results in terms of distribution of different regression grades. In univariate analysis regression gradings (P = 0.003 and P = 0.007), ypT-stage, ypN-stage and status of resection margins (P < 0.001) were significantly associated with the 5-year overall survival (OS). None of the pretreatment clinicopathological parameters showed association with histopathological tumour regression. Multivariate analysis revealed the status of resection margins and of lymph node metastasis as statistically significant features for OS (P = 0.020 and P = 0.003, respectively). CONCLUSION: Tumour regression grading, nodal stage and status of resection margins predict prognosis in patients after neoadjuvant treatment. Currently, there are no pretreatment clinicopathological parameters, which predicting good tumour response to therapy. Thus, identifying non-responding patients, which might benefit from an intensified systemic therapy, requires surgical resection and consecutive histopathological assessment. Therefore, further investigation and validation of new, especially, molecular predictors of tumour response to radiochemotherapy remains an unmet, future clinical need.

First observation of photons carrying orbital angular momentum in undulator radiation.

Photon beams of 99 eV energy carrying orbital angular momentum (OAM) have been observed in the 2nd harmonic off-axis radiation of a helical undulator at the 3rd generation synchrotron radiation light source BESSY II. For detection, the OAM carrying photon beam was superimposed with a reference beam without OAM. The interference pattern, a spiral intensity distribution, was recorded in a plane perpendicular to the propagation direction. The orientation of the observed spiral structure is related to the helicity of the undulator radiation. Excellent agreement between measurements and simulations has been found.

Carp neutrophilic granulocytes form extracellular traps via ROS-dependent and independent pathways.

Neutrophil extracellular traps (NETs) have recently been described as an important innate defense mechanism that leads to immobilization and killing of invading pathogens. NETs have been identified in several species, but the mechanisms involved in NET formation and their role in infection have not been well determined yet. Here we show that upon in vitro stimulation with different immunostimulants of bacterial, fungal or viral origin, carp neutrophilic granulocytes rapidly release NET structures. We analyzed the composition of these structures and the kinetics of their formation by confocal microscopy, by quantifying the levels of extracellular DNA and the release of enzymes originating from neutrophilic granules: myeloperoxidase, neutrophil elastase and matrix metalloproteinase 9 (MMP-9). Profiles of NET release by carp neutrophils as well as their enzyme composition are stimulus- and time-dependent. This study moreover provides evidence for a stimulus-dependent selective requirement of reactive oxygen species in the process of NET formation. Collectively the results support an evolutionary conserved and strictly regulated mechanism of NET formation in teleost fish.

Unusual coordination mode for 1,3-diphosphete ligands towards a Cr-Cr quintuple bond complex.

The reaction of LCr5̲CrL (L = N2C25H29, 1) with the phosphaalkynes R-C≡P (R = tBu, Me, Ad) yields the neutral dimerisation compounds [L2Cr2(µ,η1:η1:η2:η2-P2C2R2)] (R = tBu (2), Me (3)) and the tetrahedrane complex [L2Cr2(µ,η2:η2-PCAd)] (4). The 1,3-diphosphete ligands in complexes 2 and 3 are the first to possess this structural feature spanned over a metal-metal multiple bond, while the slightly bigger adamantyl phosphaalkyne remains a monomer in 4 with a side-on coordination mode.

Evaluation of the Neuropad sudomotor function test as a screening tool for polyneuropathy in the elderly population with diabetes and pre-diabetes: the KORA F4 survey.

BACKGROUND: Neuropad is a novel indicator test for sudomotor dysfunction, which has not been validated as a screening tool in a population-based study. This study aimed to evaluate the utility of Neuropad as a screening tool for distal symmetric polyneuropathy among elderly subjects with diabetes and pre-diabetes in the general population. METHODS: Eligible subjects aged 61-82 years (n = 940) from the KORA F4 survey were examined, 201 of whom had diabetes and 231 had pre-diabetes (WHO 1999 criteria). Polyneuropathy was defined by the Michigan Neuropathy Screening Instrument (MNSI) score >3. RESULTS: Polyneuropathy was diagnosed in 60 (29.9%) subjects with diabetes and in 45 (19.5%) subjects with pre-diabetes, respectively (p = 0.013). The sensitivity and negative predictive value of Neuropad (reading time: 10 min) for the diagnosis of polyneuropathy were moderately high, reaching 76.7% and 78.1% in subjects with diabetes and 57.8% and 76.5% in those with pre-diabetes, respectively. Conversely, the specificity and positive predictive value for the diagnosis of polyneuropathy were rather low: 35.5% and 33.6% in diabetic individuals and 33.3% and 17.3% in subjects with pre-diabetes, respectively. Use of the >2 cut-off and MNSI combined with monofilament examination did not improve the diagnostic performance of Neuropad. CONCLUSIONS: In the elderly general population with diabetes and pre-diabetes, Neuropad has reasonable sensitivity but rather low specificity for the diagnosis of polyneuropathy. It is a useful simple and inexpensive tool to screen for and to exclude polyneuropathy as desired, while its low specificity implies that a longer reading time merits consideration.

Registration accuracy of three-dimensional surface and cone beam computed tomography data for virtual implant planning.

OBJECTIVE: Virtual wax-ups based on three-dimensional (3D) surface models can be matched (i.e. registered) to cone beam computed tomography (CBCT) data of the same patient for dental implant planning. Thereby, implant planning software can visualize anatomical and prosthetic information simultaneously. The aim of this study is to assess the accuracy of a newly developed registration process. MATERIAL AND METHODS: Data pairs of CBCT and 3D surface data of 16 patients for dental implant planning were registered and the discrepancy between the visualized 3D surface data and the corresponding CBCT data were measured on 64 teeth at seven points by two investigators in two iterations with a total of 1792 measurements. RESULTS: All data pairs were matched successfully and mean distances between CBCT and 3D surface data were between 0.03(±0.33) and 0.14(±0.18) mm. At two of seven measuring points, statistically significant correlations were determined between the measured error and the presence and type of restorations. Registration errors in maxilla and mandible were not statistically significantly different. CONCLUSION: According to the results of this study, registration of 3D surface data and CBCT data works reliably and is sufficiently accurate for dental implant planning. Thereby, barium-sulfate scanning templates can be avoided and dental implant planning can be accomplished fully virtual.

Podoplanin expression in oral leukoplakia: prognostic value and clinicopathological implications.

OBJECTIVES: Current clinicopathological parameters cannot predict the risk of malignant transformation in oral leukoplakia sufficiently. Recent studies have shown that podoplanin is expressed in oral cancer and precancerous lesions. The aim of our study was to assess whether podoplanin expression in pretreatment biopsies could serve as a biomarker to predict the risk of malignant transformation in patients with oral leukoplakia. MATERIALS AND METHODS: In this retrospective study, podoplanin expression was analysed in 60 patients with previously untreated oral leukoplakia by immunohistochemistry. We investigated the associations between podoplanin expression and various clinicopathological variables including oral cancer-free survival (OCFS) and the SIN-classification. RESULTS: The chi-square-test revealed that high expression of podoplanin in pretreatment biopsies was associated with malignant transformation (P = 0.003) and increasing SIN-classification (P = 0.009). In univariate analysis, podoplanin expression in oral leukoplakia had a significant impact on OCFS (P = 0.009). The 5-year OCFS rate decreased from 100% for patients with no podoplanin expression to 41.7% for patients with the highest level of podoplanin expression. CONCLUSION: Although podoplanin expression and the SIN-classification served as factors to predict malignant transformation in patients with oral leukoplakia in univariate analysis, no significant impact was found for both factors in multivariate analysis.

Reduced incidence of blindness in relation to diabetes mellitus in southern Germany?

AIMS: We estimated the incidence of blindness in the diabetic and non-diabetic population in 2008 and compared it with results from 1990-1998 in a neighbouring region. METHODS: All newly registered blindness allowance recipients in 2008 were drawn up in a German region (population 4.5 million). We estimated sex-specific, age-specific and standardized incidence rates of blindness in the diabetic and the non-diabetic population and relative and attributable risks as a result of diabetes. A comparison to the data from 1990-1998 was performed using log-linear Poisson regression. RESULTS: Four-hundred and sixty-eight cases were drawn up (63% female). One-hundred and twenty-two (26.1%) had diabetes. Blindness incidence rates (per 100, 000 person-years) standardized to the 2008 German population were: men 9.1 (95% confidence interval 7.8-10.5), women 9.9 (8.8-11.1); diabetic population: men 21.8 (11.6-31.9), women 19.7 (9.2-30.1); non-diabetic population: men 8.0 (6.6-9.5), women 9.1 (7.9-10.3). Relative risk of blindness, diabetic vs. non-diabetic population: men 2.7 (1.6-4.5), women 2.2 (1.3-3.8). Attributable risk among exposed: 63% in men, 54% in women. Population attributable risk: 12% in men, 8% in women. Incidences of blindness were significantly lower than in all years of the period 1990-1998 in both the diabetic and the non-diabetic population. CONCLUSIONS: We found the incidence of blindness to be approximately 2.5-fold higher in the diabetic compared with the non-diabetic population. Fifty-eight per cent of the risk to become blind in diabetic individuals and 9% of the risk to become blind in the entire population were attributable to diabetes. The decrease of the blindness incidence observed during the 1990s may have continued.

Determining how diluted bloodstains were derived: Inferring distinctive characteristics and formulating a guideline.

In forensic settings, diluted bloodstains are regularly encountered for example when bloodstains are mixed with tap-/rainwater, after deliberate cleaning attempts, or when blood is dropped on a wet surface such as a towel. Such diluted bloodstain scenarios can be subdivided into sequences of events in which a blood drop was either (1) readily diluted (a mixture of blood and water is deposited); (2) deposited on a surface that was readily moistened (first water, then blood) or (3) deposited and subsequently moistened (first blood, then water). Current bloodstain pattern analysis (BPA) lacks data and tools to distinguish these three ways of derivation of a diluted bloodstain that vary in the sequence of deposition of blood and water on textile. In this study, 880 bloodstains were examined for characteristics that can be used to determine the derivation of diluted bloodstains. A guideline to assist BPA-analysts in interpreting diluted bloodstains was extracted. The added value of this guideline was confirmed by conducting two surveys: one survey with and one without the guideline. A third survey confirmed that the characteristics also function on a broader range of textile types that have different weave and knit styles. This guideline can aid BPA-experts to determine, in an objective way, how diluted bloodstains derived which can aid in determining which activities took place at a crime scene.

Management of patients with asymptomatic colorectal cancer and synchronous irresectable metastases.

BACKGROUND: In patients with asymptomatic colorectal cancer with irresectable metastatic disease, the optimal treatment strategy remains controversial. Resection of the primary tumor followed by chemotherapy when possible versus systemic chemotherapy followed by resection of the primary tumor when necessary are compared in this systematic review. PATIENTS AND METHODS: Seven studies reported series of patients with asymptomatic stage IV colorectal cancer and compared first-line chemotherapy with surgery for the primary tumor (n = 850 patients). Primary outcome measure was the complication rate related to the primary tumor in situ in patients receiving first-line systemic chemotherapy. RESULTS: When leaving the primary tumor in situ, the mean complications were intestinal obstruction in 13.9% [95% confidence interval (CI) 9.6% to 18.8%] and hemorrhage in only 3.0% (95% CI 0.95% to 6.0%) of the patients. After resection, the overall postoperative morbidity ranged from 18.8% to 47.0%. CONCLUSIONS: For patients with stage IV colorectal cancer, resection of the asymptomatic primary tumor provides only minimal palliative benefit, can give rise to major morbidity and mortality and therefore potentially delays beneficial systemic chemotherapy. When presenting with asymptomatic disease, initial chemotherapy should be started and resection of the primary tumor should be reserved for the small portion of patients who develop major complications from the primary tumor.

[Pulmonary densities following a hysterectomy, caused by benign metastatic leiomyoma]. / Pulmonale verdichtingen na een uterusextirpatie, door benigne metastatisch leiomyoom.

A 49-year-old woman, who had undergone a hysterectomy 17 years previously, was referred with thoracic pain located on the right side that had been present for several weeks. Thoracic imaging showed multiple pulmonary lesions on both sides. Histological investigation of a biopsy from one of these lesions revealed a benign metastatic leiomyoma. The patient was treated with gonadotropin-releasing hormone (GnRH) analogue. The lesions showed regression and the symptoms disappeared. Benign metastatic leiomyoma is a rare benign clinical entity in women of fertile age who have had a surgical intervention on the uterus because of uterus myomatosus. The therapeutic options are surgical resection, removal of the hormonal stimulus by administering progesterone or GnRH-analogues or bilateral ovariectomy.

Unexpected differences in the reactivity between the phosphorus and arsenic derivatives [(CpBIGFe)2(µ,η4:4-E4)] (E = P and As).

Different reaction pathways were determined between thermolysis and photolysis reactions of the butterfly complex [{CpBIGFe(CO)2}2(µ,η1:1-As4)] (1b). The thermolysis leads to novel arsenic-rich compounds [(CpBIGFe)2(µ,η4:4-As4)] (2b), [(CpBIGFe)3(µ3,η4:4:4-As6)] (4) and [CpBIGFe(η5-As5)] (5), whereas the photolysis of [{CpBIGFe(CO)2}2(µ,η1:1-E4)] (1a: E = P; 1b: E = As) exclusively results in the decarbonylation products [(CpBIGFe)2(µ,η4:4-P4)] (2a), 2b and [(CpBIGFe)(µ,η4:1-As4)(CpBIGFe(CO)2)] (3). The E4 complexes 2a and 2b show unique structural differences in the solid state despite their related compositions.

Neutral two-dimensional organometallic-organic hybrid polymers based on pentaphosphaferrocene, bipyridyl linkers and CuCl.

The reaction of the Pn ligand complex [Cp*Fe(η5-P5)] (1: Cp* = η5-C5Me5) with CuCl in the presence of 4,4'-bipyridine or 1,2-di(4-pyridyl)ethylene leads to the formation of three unprecedented neutral 2D organometallic-organic hybrid networks, the constitutional isomers [Cu2Cl2{Cp*Fe(µ3,η5:1:1-P5)}(µ,η1:1-C10H8N2)]n (2 and 3) and the coordination polymer [(CuCl)2{Cp*Fe(µ3,η5:1:1-P5)}(µ,η1:1-C12H10N2)]n (4) with isomeric square (2 and 3) and honeycomb (4) layer topologies.

Transformation of nortricyclane type cage compounds P4S3, P4Se3 and As4S3 by [Cp''2Zr(CO)2].

The complex [Cp''2Zr(CO)2] (Cp'' = C5H3tBu2) was used to transform the nortricyclane type cage compounds E4Q3 (E = P, Q = S, Se; E = As, Q = S) resulting in unprecedented complexes [(Cp''2Zr)2(µ,η1:1:1:1-E2Q4)] possessing bridging ligands that represent the anions of the so far unknown tetrachalcogenohypodiphosphorous acid (HQ)2PP(QH)2 and tetrathiohypodiarsenous acid (HS)2AsAs(SH)2, respectively.