[Salivary gland carcinomas - Monocentric experience on subtypes and their incidences over 42 years]. / Speicheldrüsenkarzinome ­ Monozentrische Erfahrung zu Subtypen und deren Inzidenz über 42 Jahre.

OBJECTIVE: Salivary gland carcinomas are rare and heterogeneous. More than 20 subtypes are recognized and risk factors are diverse. The aim of this work was to evaluate the subtype and other risk factors in a monocentric population from more than four decades. MATERIAL AND METHODS: 205 cases (diagnosis period 1972-2014) were retrospectively collected and analyzed with regard to the distribution of risk factors and their influence on overall survival (OS). RESULTS: 19/24 (79.2%) of the subtypes listed in the WHO classification occurred rarely in the cohort (< 5%). 10/24 (41.7%) of all subtypes were never diagnosed. With a total of 145/205 cases (70.7%), squamous cell carcinoma (PEC), adenocarcinoma (AdenoCa), acinar cell carcinoma (AcinarCa), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) were by far the most common subtypes. Risk factors are significantly different in these groups (e.g., lymphogenic metastasis and degree of differentiation in AdenoCa and age, T and UICC stage in PEC). The 5-year overall survival of all patients was 66.9% and differed significantly within the most common subtypes. An independent impact on overall survival was detectable for patient age (p<0.001), and T- (p=0.003) and N-stage (p=0.046) in multivariate analysis. CONCLUSIONS: Most subtypes occurred markedly rarely or not at all within decades. The most common diagnoses differ with respect to risk factors as well as OS and 3 risk groups can be defined based on histology. In conclusion, considering TNM alone is insufficient for prognosis estimation in salivary gland carcinoma.

Humoral immunogenicity of COVID-19 vaccines in patients with inflammatory rheumatic diseases under treatment with Rituximab: a case-control study (COVID-19VacRTX).

OBJECTIVES: Patients with inflammatory rheumatic diseases (IRDs) treated with the anti-CD20 mAb rituximab (RTX) have been identified as high-risk for severe COVID-19 outcomes. Additionally, there is increased risk due to reduced humoral immune response, induced by therapeutic B cell depletion. This study sought to quantify humoral response after vaccination against SARS-CoV-2 in patients with IRD treated with RTX. It also sought to elucidate the influence of the time frame between the last RTX dose and the first vaccination, or the status of B cell depletion on antibody titre. METHODS: In this case-control study, patients with IRDs previously treated with RTX were examined for humoral immune response after completing the first series of vaccinations with approved vaccines [BNT162b2 (Biontech/Pfizer), RNA-1273 (Moderna), AZD1222 (AstraZeneca/Oxford), Ad26.COV2.S (Janssen/Johnson & Johnson)]. Antibody levels were quantified using the Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (EI-S1-IgG-quant). Blood samples were taken just before the next infusion with RTX after the vaccination. The interval between the last RTX infusion and the first vaccination against SARS-CoV-2 and other possible factors influencing the antibody levels were evaluated. RESULTS: A total of 102 patients were included. Of these, 65 (64%) showed a negative antibody level (<24 IU (international unit)/ml) after the vaccination. The comparative univariate analysis of the antibody levels achieved a significant result (P = 0.0008) for the time between the last RTX infusion and first vaccination against SARS-CoV-2. No CD19+ peripheral B-cells could be detected in 73 of the patients (72%). CONCLUSION: The study confirms the negative impact of RTX on antibody level after vaccination against SARS-CoV-2. A clear relationship exists between the antibody titre and the interval between the last RTX infusion and the first vaccination, the number of peripheral B-cells, and immunoglobulin quantity. Improved understanding of the effect of these parameters can help guide synchronization of vaccination in relation to the RTX therapy regimen.

Evaluation of p16INK4a expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation.

BACKGROUND: A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16INK4a, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing. METHODS: We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV-DNA, HPV genotypes, p16INK4a expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients' survival in comprehensive uni- and multivariate analyses. RESULTS: Aetiological relevance of HPV (p16INK4a- and high-risk HPV-DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV16 being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16INK4a overexpression but no HPV-DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16INK4a-positive OPSCC lacking HPV-DNA did not resemble HPV16-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16INK4a-overexpressing OPSCC. CONCLUSIONS: p16INK4a as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.

Protective loop ileostomy increases the risk for prolonged postoperative paralytic ileus after open oncologic rectal resection.

PURPOSE: Postoperative gut dysmotility is a physiologic and frequent temporary reaction after major abdominal surgery. If paralysis merges into a prolonged ileus state, it causes significant morbidity and subsequently worse outcome and discomfort for the patients. Pathophysiology of pathologic prolonged postoperative paralytic ileus remains multifactorial. METHODS: We present a retrospective single-center analysis of patients, who underwent a primary open oncologic anterior rectal resection with primary anastomosis with or without defunctioning loop ileostomy during a 43-month period of observation. Primary endpoint was the rate of prolonged postoperative paralytic ileus, defined by the intravenous administration of neostigmine. Confounders for regression analysis were assessed by univariate analysis and correlations between confounders were examined. Odds ratio for prolonged postoperative paralytic ileus in patients with defunctioning loop ileostomy was estimated by a logistic regression model. RESULTS: Of 101 patients (62 male), 62 (61.39%) received defunctioning loop ileostomy. In univariate analysis, male gender and patients with ileostomy showed more frequently prolonged paralysis by tendency (both p = 0.07). Logistic regression analysis proves the influence of a defunctioning ileostomy on the development of prolonged postoperative paralytic ileus after oncologic rectal resection (p = 0.047). Odds ratio for prolonged postoperative paralytic ileus in patients with ileostomy was 4.96 [95% CI 1.02-24.03]. CONCLUSIONS: Although the construction of defunctioning loop ileostomies during rectal resection is a safe, uncomplicated surgical procedure, they can cause significant postoperative morbidity for the patients. High fluid and electrolyte loss are well-known complications, but herewith we raise the evidence for prolonged gut paralysis in patients with defunctioning loop ileostomy.

Thoracotomy versus video-assisted thoracoscopic surgery (VATS) in stage III empyema-an analysis of 217 consecutive patients.

BACKGROUND: Pleural empyema is an infectious disease of the chest cavity, with a high morbidity and mortality. According to the American Thoracic Society, pleural empyema gets graduated into three stages, with surgery being indicated in intermediate stage II and chronic stage III. Evidence for the feasibility of a minimally-invasive video-assisted thoracoscopic approach in stage III empyema for pulmonary decortication is still little. METHODS: Retrospective single-center analysis of patients conducted to surgery for chronic stage III pleural empyema from 05/2002 to 04/2014 either by video-assisted thoracoscopic surgery (VATS, n = 110) or conventional open surgery by thoracotomy (n = 107). Multiple regression analysis and propensity score matching was used to evaluate the influence of operation technique (thoracotomy versus VATS) on the length of post-operative hospitalization. RESULTS: Operation time was longer in the thoracotomy-group (p = 0.0207). Conversion rate from VATS to open surgery by thoracotomy was 4.5%. Post-operative complication- (61 patients in thoracotomy- and 55 patients in VATS-group), recurrence- (3 patients in thoracotomy- and 5 in VATS-group) and mortality-rates (6.5% in thoracotomy- and 9.5% in VATS-group) did not differ between both groups; the length of (post-operative) stay at intensive care unit was longer in the VATS-group (p = 0.0023). Duration of chest tube drainage and prolonged air leak rate were similar among both groups, leading to a similar overall and post-operative length of hospital stay in both groups. Adjusted to clinically and statistically relevant confounders, multiple regression analysis showed an influence of the surgical technique on length of post-operative stay after pair matching of the patients (n = 84 in each group) by propensity score (B = - 0.179 for thoracotomy = 0 and VATS = 1, p = 0.032) leading to a reduction of 0.836 days after a VATS-approach compared to thoracotomy. CONCLUSIONS: VATS in late stage (III) pleural empyema is feasible and safe. The decrease in post-operative hospitalization demonstrated by adjusted multiple regression analysis may indicate the minimally-invasive approach being safe, more tolerable for patients, and more effective.

Speckle Tracking in Transcranial Ultrasound Allows Noninvasive Analysis of Pulsation Patterns of the Third Ventricle.

Cerebrospinal fluid (CSF) flow is sensitive to many cerebral disorders. We aimed to develop a noninvasive bedside method to detect physiological and pathological CSF phenomena by measuring pulsation patterns of the third ventricle. By transcranial B-mode ultrasound, electrocardiography (ECG)-gated video loops of the third ventricle were acquired. "Speckle tracking" software was used to quantify the relative change of its width. We conducted measurements of nine cardiac cycles in 11 healthy subjects in sitting and in supine position during Valsalva maneuver to investigate the influence of an increased intracranial pressure on the relative deformation of the third ventricle. In one patient with occlusive hydrocephalus, 19 cardiac cycles were measured in sitting position before and after removal of a tumorous obstruction of the aqueduct of Sylvius. Healthy subjects expressed a pulse-related increased width of the third ventricle ([Formula: see text]: +5.69, 95% confidence interval [CI] = [4.38, 7.00]). No significant difference was found between the sitting and the supine position in healthy adults. In the preoperative state of occlusive hydrocephalus, we found a negative, pulse-related deformation ([Formula: see text]: -1.86, 95% CI = [-2.15, -1.58]) with delayed onset. After surgery, the deformation pattern resembled that of our healthy controls. The difference between pre- and postoperative condition was significant (p < 0.001). Transcranial B-mode sonography can be used to record small movements of the sidewalls of the third ventricle. This noninvasive bedside method is suitable to assess CSF pulsatility within the third ventricle and might be able to distinguish between physiological and pathological flows.

Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer.

BACKGROUND: Upfront surgery is a valuable treatment option for oropharyngeal squamous cell carcinoma (OPSCC) and risk stratification is emerging for treatment de-escalation in human papillomavirus (HPV)-related OPSCC. Available prognostic models are either based on selected, mainly non-surgically treated cohorts. Therefore, we investigated unselected OPSCC treated with predominantly upfront surgery. METHODS: All patients diagnosed with OPSCC and treated with curative intent between 2000 and 2009 (n=359) were included. HPV association was determined by HPV-DNA detection and p16INK4a immunohistochemistry. Predictors with significant impact on overall survival (OS) in univariate analysis were included in recursive partitioning analysis. RESULTS: Risk models generated from non-surgically treated patients showed low discrimination in our cohort. A new model developed for unselected patients predominantly treated with upfront surgery separates low-, intermediate- and high-risk patients with significant differences in 5-year OS (86%, 53% and 19%, P<0.001, respectively). HPV status is the most important parameter followed by T-stage in HPV-related and performance status in HPV-negative OPSCC. HPV status and ECOG remained important parameters in risk models for patients treated with or without surgery. CONCLUSIONS: Regardless of treatment strategies, HPV status is the strongest predictor of survival in unselected OPSCC patients. The proposed risk models are suitable to discriminate risk groups in unselected OPSCC patients treated with upfront surgery, which has substantial impact for design and interpretation of de-escalation trials.

Effects of Traumeel (Tr14) on recovery and inflammatory immune response after repeated bouts of exercise: a double-blind RCT.

PURPOSE: The purpose of this double-blind, randomized, placebo-controlled clinical trial was to investigate the effects of the natural combination medicine Traumeel (Tr14) consisting of 14 diluted biological and mineral components on the inflammatory immune response and recovery up to 72 h after repetitive bouts of bicycle tests. METHODS: Antigen-stimulated IL-1ra and IL-6 were defined as primary outcome measures. Moreover, various immunological and serum muscle damage markers were investigated. The evaluation was performed using the score of the area under the curve with respect to increase (AUCi) for 24 and 72 h after the second exercise test (EX2). RESULTS: The Tr14 group indicated a lower decrease of lymphocytes by tendency (p = 0.06) and a lower activation of lymphocyte activation markers (CD62L absolute: p = 0.04; CD69: p = 0.01 and CD69 absolute: p = 0.05) in the period 24 h after EX2. In addition, the Tr14 group indicated a higher expression of antigen-stimulated CCL3 (p = 0.01), CCL4 (p = 0.07) and serum CCL2 (p = 0.05) in the period 24 h after EX2. There was a tendentially lower decrease of monocytes (p = 0.09) and a lower expression of antigen-stimulated MMP-3 (p = 0.01) in the Tr14 group in the period 72 h after EX2. However, antigen-stimulated IL-1ra and IL-6 showed no group differences. CONCLUSION: In line with the previous results, it was shown that Tr14 attenuates the adaptive immune response partially. Furthermore, the results indicate that Tr14 is able to stimulate the innate immune system via an increased production of pro-inflammatory chemokines. It is speculated that the higher expression of chemokines might play a role in the regeneration and recovery after exercise.

Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT.

The present double-blind, randomized, placebo-controlled clinical trial intended to test whether ingestion of a natural combination medicine (Tr14 tablets) affects serum muscle damage and inflammatory immune response after downhill running. 96 male subjects received Tr14 tablets, which consist of 14 diluted biological and mineral components, or a placebo for 72 h after the exercise test, respectively. Changes in postexercise levels of various serum muscle damage and immunological markers were investigated. The area under the curve with respect to the increase (AUCi) of perceived pain score and creatine kinase (CK) were defined as primary outcome measures. While for CK the p value of the difference between the two groups is borderline, the pain score and muscle strength were not statistically significant. However, a trend towards lower levels of muscle damage (CK, p = 0.05; LDH, p = 0.06) in the Tr14 group was shown. Less pronounced lymphopenia (p = 0.02), a trend towards a lower expression of CD69 count (p = 0.07), and antigen-stimulated ICAM-1 (p = 0.01) were found in the verum group. The Tr14 group showed a tendentially lower increase of neutrophils (p = 0.10), BDNF (p = 0.03), stem cell factor (p = 0.09), and GM-CSF (p = 0.09) to higher levels. The results of the current study indicate that Tr14 seems to limit exercise-induced muscle damage most likely via attenuation of both innate and adaptive immune responses. This study was registered with ClinicalTrials.gov (NCT01912469).

Microsurgical unilateral laminotomy for decompression of lumbar spinal stenosis: long-term results and predictive factors.

BACKGROUND: The microsurgical unilateral laminotomy (MUL) technique for bilateral decompression of lumbar spinal stenosis (LSS) is a less destabilizing alternative to laminectomy and leads to good short-term outcomes. However, little is known about the long-term results including predictive factors. METHODS: Medical records of patients who underwent MUL for LSS decompression between 2005 and 2010 were reviewed, and a questionnaire was distributed to complement the long-term outcome data. The study population consisted of 176 patients including 17 patients with stable grade I spondylolisthesis. Complications and reoperations were meticulously analyzed. Clinical outcome was measured using a modified Prolo scale and was further dichotomized in good vs. poor outcome. Predictive factors were obtained from uni- and multivariate analyses. RESULTS: The median age of the cohort was 70.0 years and the follow-up 71.7 months. Complications occurred in 5.1 % of the patients. The overall reoperation rate was 17.0 %, including surgery, which was exclusively performed at other levels in 4.0 %. The reoperation rate for fusion was 4.5 %. Good neurogenic claudication outcome faded from 98.3 % at hospital discharge to 47.2 % at 6 years. Multivariate analysis identified previous lumbar operation as a potential independent predictor of a reoperation; potential independent predictors of poor long-term claudication outcome were older age, female gender, higher body mass index (BMI) and tobacco smoking. CONCLUSIONS: In our experience, the long-term reoperation rate after MUL for LSS is not negligible and higher in previously operated patients. It seems like the good initial clinical results after MUL may fade over time, and several patient-related predictive factors including potentially modifiable obesity and tobacco smoking seem to play an important role.

Treated Versus Untreated Positional Head Deformity.

BACKGROUND: Positional head deformity in early childhood is asserted to be a benign and in some cases spontaneously correcting entity encountered in craniofacial surgery. Although many authors have stated that helmet therapy is indicated in moderate and severe cases of deformational plagiocephaly and brachycephaly; others have reported resolution of these conditions within the first 2 to 3 years of life. A recent randomized controlled trial found that helmet therapy does not have beneficial effects for patients with positional head deformity. METHODS: The authors evaluated the clinical course of positional cranial deformation during a period of 5 years and compared the anthropometric parameters of orthotically treated versus untreated children within this timeframe. RESULTS: Although the patients were matched with respect to their cranial deformation at baseline, there were significant differences in the cranial vault asymmetry (CVA), cranial vault asymmetry index (CVAI), and oblique cranial length ratio (OCLR) between Groups 1 and 2 at the initial point (P < 0.05). The mean CVA was 0.95 cm in Group 1 (no helmet) and 1.74 cm in Group 2 (helmet). The mean CVAI at baseline was 7.25 for Group 1 and 13.77 for Group 2. Approximately 5 years after the first examination, the authors found clear improvement in the mean CVA in Group 2 (ΔCVA 1.35 cm) compared with Group 1 (ΔCVA 0.01 cm) and the mean CVAI. CONCLUSIONS: In contrast to recently published studies, the authors found clear improvement in nonsynostotic head deformity treated with an individual molding helmet and no clear evidence of improvement of absolute measurements in untreated cranial deformity within a 5-year follow-up period.

Preventive strength training improves working ergonomics during welding.

To investigate the effect of a preventive strength training program on cardiovascular, metabolic and muscular strains during welding. Welders are one of the occupation groups which typically have to work in extended forced postures which are known to be an important reason for musculoskeletal disorders. Subjects (exercise group) accomplished a 12-week strength training program, while another group served as controls (control group). Pre and post training examinations included the measurements of the one repetition maximum and an experimental welding test. Local muscle activities were analysed by surface electromyography. Furthermore, heart rate, blood pressure, lactate and rating of perceived exertion were examined. In the exercise group, strength training lead to a significant increase of one repetition maximum in all examined muscles (p<.05). During the experimental welding test muscle activities of trunk and shoulder muscles and arm muscles were significantly reduced in the exercise group after intervention (p<.05). While no changes of neither cardiovascular nor metabolic parameters were found, subjects of the exercise group rated a significantly decreased rate of perceived exertion welding (p<.05). Effects of strength training can be translated in an improved working ergonomics and tolerance against the exposure to high physical demands at work.

Normative values of peripheral retinal thickness measured with Spectralis OCT in healthy young adults.

BACKGROUND: To evaluate the range of peripheral retinal thickness (PRT) in young healthy human subjects by Spectralis HRA + OCT, and to analyze a potential association between the peripheral location, spherical equivalent (SE), axial length (AL), and gender. METHODS: After pupil dilation, the peripheral retina was scanned by means of six volume protocols (9 × 7.5 mm), each consisting of 31 B-scans. PRT was determined at 4,500, 5,500, 6,500 and 7,500 µm eccentricity from the fovea and the optic nerve head (ONH). Data points were collected every 22.5°. Six additional data points at a distance of 9,000 µm were included. In 11 subjects, OCT measurements were performed twice to evaluate reproducibility. Coefficients of variation (COV) were calculated. RESULTS: Randomly selected eyes of 50 subjects (19-30 years) with AL of 21-27 mm (SE: -5.75 to +5.25 dpt) were included in the study. Mean PRT decreased significantly (p ≤ 0.001, r = -0.99) towards the periphery, reaching a minimum at 9,000 µm eccentricity (mean PRT: 187.7 ± 8.9 µm). Multiple regression analysis revealed a significant association of PRT with AL at nasal and temporal locations as well as gender for temporal locations. COVs ranged from 0.44 to 2.90 %, with highest COVs found nasal to the fovea. CONCLUSIONS: This is the first study to report normative data of PRT outside the ETDRS grid and to show a significant continuous almost linear decrease of the RT from the center into the periphery. The data will be valuable to detect peripheral pathologies of the retina in early stages of peripheral retinal dystrophies.

Schistosoma mansoni-Induced Oxidative Stress Triggers Hepatocellular Proliferation.

BACKGROUND & AIMS: Schistosomiasis is one of the most prominent parasite-induced infectious diseases, affecting more than 250 million people. Schistosoma mansoni causes metabolic exhaustion and a strong redox imbalance in the liver, causing parenchymal damage, and may predispose for cancer. We investigated whether oxidative stress provokes hepatocellular proliferation upon S. mansoni infection. METHODS: The cell cycle, replication stress response, and proliferation were analyzed on transcriptional and protein levels in the livers of S. mansoni-infected hamsters and by mechanistic gain- and loss-of-function experiments in human hepatoma cells. Major results were validated in human biopsy specimens of S. mansoni-infected patients. RESULTS: S. mansoni infection induced licensing factors of DNA replication and cell-cycle checkpoint cyclins in parallel with a DNA damage response in hamster hepatocytes. Moreover, even unisexual infection without egg effects, as a reflection of a chronic inflammatory process, resulted in a moderate activation of several cell-cycle markers. S. mansoni soluble egg antigens induced proliferation of human hepatoma cells that could be abolished by reduced glutathione. CONCLUSIONS: Our data suggest that hepatocellular proliferation is triggered by S. mansoni egg-induced oxidative stress.

Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping.

BACKGROUND: Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS. METHODS: We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing's disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female). FINDINGS: Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(11ß-OH-An + 11ß-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%. INTERPRETATION: GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes. FUNDING: The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung.

MCT-Induced Ketosis and Fiber in Rheumatoid Arthritis (MIKARA)-Study Protocol and Primary Endpoint Results of the Double-Blind Randomized Controlled Intervention Study Indicating Effects on Disease Activity in RA Patients.

Fatty acids, such as medium-chain fatty acids (MCFAs) and short-chain fatty acids (SCFAs), both important components of a normal diet, have been reported to play a role in bone-related diseases such as rheumatoid arthritis (RA). However, the role of medium-chain triglycerides (MCTs) has not been investigated in RA to date. The aim of this study was to investigate the effect of supplementation of regular diet with MCT with and without fiber on disease activity as measured with the SDAI (Simplified Disease Activity Index) in RA patients. A total of 61 RA patients on stable drug treatment were randomly assigned to a twice-daily control regimen or to a twice-daily regimen of a formulation containing medium-chain triglycerides (MCTs) 30 g/day for 8 weeks followed by a second twice-daily regimen of combining MCT (30 g/day) plus fiber (30 g/day) for an additional 8 weeks. The control group received a formulation containing long-chain triglycerides (LCTs) instead of MCTs. The preliminary results showed a significant reduction in SDAI from baseline to week 16 in the test group and a significant increase in ß-hydroxybutyrate (BHB) levels, while no improvement in SDAI was observed in the control group.

Predictors for Survival of Patients with Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region.

BACKGROUND: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. METHODS: We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000-2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. RESULTS: In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. CONCLUSIONS: Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles.