Standardized Diagnostic Workup and Patient-Centered Decision Making for Surgery and Neck Dissection Followed by Risk-Factor Adapted Adjuvant Therapy Improve Loco-Regional Control in Local Advanced Oral Squamous Cell Carcinoma

BackgroundStandardized staging procedures and presentation of oral squamous cell carcinoma (OSCC) patients in multidisciplinary tumor boards (MDTB) before treatment and utilization of elective neck dissection (ND) are expected to improve the outcome, especially in local advanced LAOSCC (UICC stages III–IVB). As standardized diagnostics but also increased heterogeneity in treatment applied so far have not been demonstrated to improve outcome in LAOSCC, a retrospective study was initiated.MethodsAs MDTB was introduced into clinical routine in 2007, 316 LAOSCC patients treated during 1991-2017 in our hospital were stratified into cohort 1 treated before (n=104) and cohort 2 since 2007 (n=212). Clinical characteristics, diagnostic procedures and treatment modality of patients were compared using Chi-square tests and outcome analyzed applying Kaplan-Meier plots and log-rank tests as well as Cox proportional hazard regression. Propensity scores (PS) were used to elucidate predictors for impaired distant metastasis-free survival (DMFS) in PS-matched patients.ResultsMost patient characteristics and treatment modalities applied showed insignificant alteration. Surgical treatment included significantly more often resection of the primary tumor plus neck dissection, tracheostomy and percutaneous endoscopic gastrostomy tube use. Cisplatin-based chemo-radiotherapy was the most frequent. Only insignificant improved disease- (DFS), progression- (PFS) and event-free (EFS) as well as tumor-specific (TSS) and overall survival (OS) were found after 2006 as local (LC) and loco-regional control (LRC) were significantly improved but DMFS significantly impaired. Cox regression applied to PS-matched patients elucidated N3, belonging to cohort 2 and cisplatin-based chemo-radiotherapy as independent predictors for shortened DMFS. The along chemo-radiotherapy increased dexamethasone use in cohort 2 correlates with increased DM.ConclusionsDespite standardized diagnostic procedures, decision-making considering clear indications and improved therapy algorithms leading to improved LC and LRC, shortened DMFS hypothetically linked to increased dexamethasone use had a detrimental effect on TSS and OS.

Non-Celiac Gluten Sensitivity in Children: Controversial Role of Gluten and Diagnostic Enigma

Non-celiac gluten sensitivity (NCGS) is a debatable condition that affects less than 6% of children. The absence of specific diagnostic markers and standardized diagnostic procedures make the diagnosis of NCGS challenging, covering patients with different and varied symptoms. Generally, the parents of small and younger children introduce a gluten-free diet (GFD) based on their personal experiences and expectations. Additionally, a “fad component” exists, contributing to the recent rise in the popularity of GFD. Thus, celiac disease (CD) and wheat allergy (WA) must be excluded as these also appear in individuals experiencing symptoms similar to those of NCGS, improving and worsening with gluten withdrawal and consumption, respectively. The role of gluten inducing gastrointestinal symptoms in individuals with self-reported NCGS has been skeptically assessed based on evidence in recent years. However, currently, it is unknown whether a strict GFD is necessary for patients with NCGS. Thus, the placebo-controlled gluten challenge remains the gold standard for a challenging diagnosis like NCGS. The present review evaluates the published studies based largely on the adult population and describes the key elements in diagnosing NCGS and differential diagnosis with CD and WA.

Novedades acerca de los trastornos motores del esófago tras la reciente clasificación de chicago 4.0

The Chicago Classification includes esophageal motor disorders diagnosed by high-resolution manometry. Of the manometric patterns, some are always clinically relevant and require treatment (eg, the achalasia), while others may be incidental findings requiring no intervention in which aggressive management would be counterproductive. One of the goals of the new version of the recently published Chicago Classification (CCv4.0) was to distinguish between clinically relevant and non-clinically relevant disorders. With this in mind, the study protocol was modified to include liquid swallows in the supine and sitting positions and provocation tests were standardized. Diagnostic criteria were modified, incorporating the presence of symptoms and the support of complementary studies other than manometry. In this review, we will comment the diagnosis and treatment of esophagogastric junction outlet obstruction and hypomotility disorders based on CCv4.0.

Standardized Diagnostics Including PET-CT Imaging, Bilateral Tonsillectomy and Neck Dissection Followed by Risk-Adapted Post-Operative Treatment Favoring Radio-Chemotherapy Improve Survival of Neck Squamous Cell Carcinoma of Unknown Primary Patients

BackgroundAbout five to 10% of cancers in the head and neck region are neck squamous cell carcinoma of unknown primary (NSCCUP). Their diagnosis and treatment are challenging given the risk of missing occult tumors and potential relapse. Recently, we described human papillomavirus (HPV)-related NSCCUP-patients (NSCCUP-P) as a subgroup with superior survival. However, standardized diagnostic workup, novel diagnostic procedures, decision-making in the multidisciplinary tumor board (MDTB) and multimodal therapy including surgery and post-operative radio-chemotherapy (PORCT) may also improve survival.MethodsFor assessing the impact of standardized diagnostic processes simultaneously established with the MDTB on outcome, we split our sample of 115 NSCCUP-P into two cohorts treated with curative intent from 1988 to 2006 (cohort 1; n = 53) and 2007 to 2018 (cohort 2; n = 62). We compared diagnostic processes and utilized treatment modalities applying Chi-square tests, and outcome by Kaplan–Meier plots and Cox regression.ResultsIn cohort 2, the standardized processes (regular use of [18F]-FDG-PET-CT imaging followed by examination under anesthesia, EUA, bilateral tonsillectomy and neck dissection, ND, at least of the affected site) improved detection of primaries (P = 0.026) mostly located in the oropharynx (P = 0.001). From 66.0 to 87.1% increased ND frequency (P = 0.007) increased the detection of extracapsular extension of neck nodes (ECE+) forcing risk factor-adapted treatment by increased utilization of cisplatin-based PORCT that improved 5-years progression-free and overall survival from 60.4 and 45.3 to 67.7% (P = 0.411) and 66.1% (P = 0.025).ConclusionsStandardized diagnostic workup followed by ND and risk-factor adapted therapy improves survival of NSCCUP-P.

How We Approach: Pediatric Congenital Chylous Effusions and Ascites

Congenital lymphatic leak may develop in patients with maldeveloped lymphatics and result in life-threatening fluid and electrolyte imbalance, protein deficiency and immunodeficiency. Rapid diagnosis and therapy are necessary to prevent these complications; however, the field lacks clinical trials to support standardized diagnostic treatment guidelines. We present our current multidisciplinary approach to the diagnosis and management of congenital lymphatic leak including chylous pleural effusion and ascites. Depending on the rate of lymphatic leak, therapy can range from observation with nutritional modifications to surgical and interventional procedures aimed to reduce lymphatic drainage. Modalities to image central and peripheral lymphatics have advanced considerably. Genetic variants and subsequent targets that drive lymphatic maldevelopment have expanded the repertoire of possible pharmacotherapeutic options.

ADOS-Eye-Tracking: The Archimedean Point of View and Its Absence in Autism Spectrum Conditions

Face perception and emotion categorization are widely investigated under laboratory conditions that are devoid of real social interaction. Using mobile eye-tracking glasses in a standardized diagnostic setting while applying the Autism Diagnostic Observation Schedule (ADOS-2), we had the opportunity to record gaze behavior of children and adolescents with and without Autism Spectrum Conditions (ASCs) during social interaction. The objective was to investigate differences in eye-gaze behavior between three groups of children and adolescents either (1) with ASC or (2) with unconfirmed diagnosis of ASC or (3) with neurotypical development (NTD) during social interaction with an adult interviewer in a diagnostic standard situation using the ADOS-2. In a case control study, we used mobile eye-tracking glasses in an ecologically valid and highly standardized diagnostic interview to investigate suspected cases of ASC. After completion of the ASC diagnostic gold standard including the ADOS-2, the participants were assigned to two groups based on their diagnosis (ASC vs. non-ASC) and compared with a matched group of neurotypically developed controls. The primary outcome measure is the percentage of total dwell times assessed for different areas of interest (AOI) with regard to the face and body of a diagnostic interviewer and the surrounding space. Overall, 65 children and adolescents within an age range of 8.3–17.9 years were included in the study. The data revealed significant group differences, especially in the central-face area. Previous investigations under laboratory conditions gave preferential attention to the eye region during face perception to describe differences between ASC and NTD. In this study – using an ecologically valid setting within a standard diagnostic procedure – the results indicate that neurotypically developed controls seem to process faces and facial expressions in a holistic manner originating from the central-face region. Conversely, participants on the Autism Spectrum (tAS) seem to avoid the central-face region and show unsystematic gaze behavior, not using the preferred landing position in the central-face region as the Archimedean point of face perception. This study uses a new approach, and it will be important to replicate these preliminary findings in future research.

Persons with co-existing neurological disorders: Risk analysis, considerations and management in COVID-19 pandemic

: Increasing reports of neurological symptoms in COVID-19 patient’s warrant clinicians to adopt and define the standardized diagnostic and managing protocols in order to investigate the linkage of neurological symptoms in COVID-19. Encephalitis, anosmia, acute cerebrovascular disease and ageusia are some of the emerging neurological manifestations which are reported in several cohort studies on hospitalized patients with COVID-19. Although the COVID-19 pandemic is primarily associated with respiratory tract system but measures like lockdown and restricted physical movements to control the spread of this infection will certainly have neurobehavioural implications. Additionally, some of the patients with pre-existing neurological manifestations like epilepsy, Parkinson’s and Alzheimer’s disease are more prone to infection and demands extra as well as improvisation in their treatment therapy. In this review we have focused on the neurovirological clinical manifestations associated with COVID-19 pandemic. Although the prevalence of neurovirological manifestations is rare but increasing reports cannot be ignored and needs to be discussed thoroughly with respect to risk analysis and considerations for developing management strategy. This also helps in defining the burden of neurological disorders associated with COVID-19 patients.

Is the Frontal Lobe the Primary Target of SARS-CoV-2?

Acute delirium and other neuropsychiatric symptoms have frequently been reported in COVID-19 patients and are variably referred to as acute encephalopathy, COVID-19 encephalopathy, SARS-CoV-2 encephalitis, or steroid-responsive encephalitis. COVID-19 specific biomarkers of cognitive impairment are currently lacking, but there is some evidence that SARS-CoV-2 could preferentially and directly target the frontal lobes, as suggested by behavioral and dysexecutive symptoms, fronto-temporal hypoperfusion on MRI, EEG slowing in frontal regions, and frontal hypometabolism on 18F-FDG-PET imaging. We suggest that an inflammatory parainfectious process targeting preferentially the frontal lobes (and/or frontal networks) could be the underlying cause of these shared clinical, neurophysiological, and imaging findings in COVID-19 patients. We explore the biological mechanisms and the clinical biomarkers that might underlie such disruption of frontal circuits and highlight the need of standardized diagnostic procedures to be applied when investigating patients with these clinical findings. We also suggest the use of a unique label, to increase comparability across studies.

The Importance of Multimodality Imaging in the Diagnosis and Management of Patients with Infiltrative Cardiomyopathies: An Update

Infiltrative cardiomyopathies (ICMs) comprise a broad spectrum of inherited and acquired conditions (mainly amyloidosis, sarcoidosis, and hemochromatosis), where the progressive buildup of abnormal substances within the myocardium results in left ventricular hypertrophy and manifests as restrictive physiology. Noninvasive multimodality imaging has gradually eliminated endomyocardial biopsy from the diagnostic workup of infiltrative cardiac deposition diseases. However, even with modern imaging techniques’ widespread availability, these pathologies persist in being largely under- or misdiagnosed. Considering the advent of novel, revolutionary pharmacotherapies for cardiac amyloidosis, the archetypal example of ICM, a standardized diagnostic approach is warranted. Therefore, this review aims to emphasize the importance of contemporary cardiac imaging in identifying specific ICM and improving outcomes via the prompt initiation of a targeted treatment.