Search

In the last two decades there has been significant progress in research on and diagnosis of hepatocellular adenoma (HCA), resulting in the establishment of a molecular and immunohistological HCA classification. This review aims to fine-tune the current expertise in order to enhance the histopathological diagnostic possibilities, by refining issues that are already known, addressing diagnostic difficulties, and identifying still unknown aspects of HCA. We discuss novel methods to identify HCA subtypes, in particular the sonic hedgehog HCAs and the interpretation of glutamine synthetase patterns for the recognition of β-catenin-mutated HCAs. The major complications of HCAs, i.e. bleeding and malignant transformation, are considered, including the dilemmas of atypical and borderline lesions. HCAs in different clinical and geographical settings, e.g. pregnancy, cirrhosis and non-western countries, are also discussed. The natural history of the different HCA subtypes in relation to age, sex and risk factors is a feature that is still insufficiently investigated. This is also true for the risks of clinical bleeding and malignant transformation in association with HCA subtypes. As HCA is a relatively rare tumour, a multicentre and multidisciplinary approach across geographical boundaries will be the appropriate method to establish prospective programmes with which to identify, classify and manage HCAs, focusing on several aspects, e.g. aetiology, underlying liver disease, complications, regression, and growth. Updating what we know and identifying and addressing what we do not know matters for optimal patient management.

Bedside ultrasound has been shown to change and direct patient management in the emergent setting. Demand, use, and diagnostic potential of point-of-care ultrasound (POCUS) has continually increased throughout the years. The ongoing COVID-19 pandemic and physical distancing have necessitated further POCUS innovation. With the advent of affordable portable ultrasound devices, teleultrasound teaching has become a more viable method of POCUS education, especially in resource-limited settings. Here, we provide a scoping review of the current state of teleultrasound, specifically its use for educational purposes.

An intraoperative power failure (IOPF) is a complete or partial absence of the electrical power supply with or without the availability of a backup generator system during an operative or other invasive procedure. An IOPF can be stressful for the OR team and puts surgical patients at risk for adverse outcomes. To prepare providers for an IOPF, a CRNA piloted a project to create an evidence-based, facility-specific cognitive aid (CA) to guide decision making and enhance patient management and outcomes during an IOPF. The project team tested the battery-power capabilities of essential anesthesia equipment, including anesthesia gas machines, IV pumps, and vital sign monitors, and included the results in the CA. A needs assessment survey was sent to the anesthesia professionals at the facility to promote clinician buy-in and solicit feedback for creating the CA.

OBJECTIVE To examine the impact of first-trimester crown-rump length (CRL) measurement error on the interpretation of estimated fetal weight (EFW) and classification of fetuses as small-, large- or appropriate-for-gestational age on subsequent growth scans. METHODS We examined the effects of errors of ± 2, ± 3 and ± 4 mm in the measurement of fetal CRL on percentiles of EFW at 20, 32 and 36 weeks' gestation and classification as small-, large- or appropriate-for-gestational age. Published data on CRL measurement error were used to determine variation present in practice. RESULTS A measurement error of -2 mm in first-trimester CRL shifts an EFW on the 10th percentile at the 20-week scan to around the 20th percentile, and the effect of a CRL measurement error of + 2 mm would shift an EFW on the 10th percentile to around the 5th percentile. At 32 weeks, a first-trimester CRL measurement error would shift an EFW on the 10th percentile to the 7th (+ 2 mm) or 14th (-2 mm) percentile; at 36 weeks, the EFW would shift from the 10th percentile to the 8th (+ 2 mm) or 12th (-2 mm) percentile. Published data suggest that measurement errors of 2 mm or more are common in practice. CONCLUSION Because of the widespread and potentially severe consequences of CRL measurement errors as small as 2 mm on clinical assessment, patient management and research results, there is a need to increase awareness of the impact of CRL measurement error and to reduce measurement error variation through standardization and quality control. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

To investigate the current experience and expertise for haemophilia inhibitor patient management in haemophilia treatment centres (HTCs) in mainland China. Questionnaires were distributed to 'tertiary tier A' hospital HTCs across China to collect information on treatment preferences for bleeding control, prophylaxis and inhibitor eradication, as well as their regimens in real-world clinical practice. Of 40 questionnaires distributed, 39 were returned. In all, 38 were analysable for treatment preferences and 34 for actual clinical practice. For haemostatic treatment, 76·3% (29/38) HTCs preferred activated recombinant human Factor VII (rFVIIa). In clinical practice, the most widely used by-pass agent was prothrombin complex concentrate (26 HTCs). Although 65·8% (25/38) of HTCs believed prophylaxis treatment was necessary, it was prescribed in only 12. Similarly, 65·8% (25/38) of HTCs believed immune tolerance induction (ITI) therapy was necessary but only 14·8% (92/622) of patients in 19 HTCs received low-dose ITI treatment. HTCs in relatively economically developed cities (with higher-than-average per-capita gross domestic product) had better access to haemostatic treatment, coagulation testing and were more likely to provide prophylaxis and ITI in practice. The present survey showed there were gaps in haemophilia inhibitor care between the HTC physicians' preferences and their actual clinical practice. More specific care guidelines, education and clinical decision support tools are needed to guide clinical practice.

Color flow Doppler ultrasound is a critical tool in the assessment of the scrotum. Ultrasound is the first-line imaging modality and can rapidly differentiate between surgical and nonsurgical conditions, allowing for appropriate and prompt patient management. We review the role of color flow Doppler in the evaluation of acute scrotal pain, highlighting some of the most commonly seen pathologies such as epididymo-orchitis and testicular torsion.

Mantle cell lymphoma (MCL) is clinically characterized by its heterogenous behavior with courses ranging from indolent cases that do not require therapy for years to highly aggressive MCL with very limited prognosis. A better understanding of the complex biology of MCL has already led to the approval of several innovative agents, expanding the landscape of MCL therapies and improving therapeutic options especially for refractory or relapsed disease. Nevertheless, to further optimize MCL treatment, early identification of individual risk profile and risk-adapted, patient-tailored choice of therapeutic strategy needs to be prospectively incorporated in clinical patient management. This review highlights recent advances in deciphering the molecular background of MCL, the definition of prognostically relevant factors and the identification of potential druggable targets and summarizes current treatment recommendations for primary and relapsed/refractory MCL including novel targeted therapies.

Background Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha‐fetoprotein (AFP) is a well‐established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static AFP values is limited and the clinical potential is a matter of ongoing scientific discussion. Objective We here evaluated the prognostic impact of pretreatment static and dynamic AFP variables on overall survival of hepatocellular carcinoma patients in a Western cohort. Methods Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg University Mainz between 1998 and 2014 and two available pretreatment AFP‐values (AFP‐slope) were retrospectively analysed. Clinicopathological baseline parameters, pretreatment static values and AFP‐slope were assessed. Prognostic impact was determined by Kaplan–Meier analyses and Cox regression models. Results High static and dynamic AFP variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child–Pugh B (p < 0.01) and C stage (p, Key Summary Alpha‐fetoprotein (AFP) is the most commonly used biomarker for hepatocellular carcinomas (HCCs), but accuracy of static and dynamic AFP values is limited and the prognostic significance is under debate.High static and dynamic AFP variables prior to therapy are associated with reduced survival rates of HCC patients across different tumour stages and treatment modalities.In patients with more favourable prognosis, AFP‐slope prior to therapy was a better predictor for overall survival in comparison with static AFP values.Addition of AFP‐slope to established prognostic parameters might improve prognostic classification for a subgroup of HCC.

In the dermatologic medical literature, there is an underrepresentation of conditions in individuals of color. Due to the lack of representation, it may be harder for clinicians to recognize certain diagnoses in patients with darker skin phototypes leading to misdiagnosis and affecting overall patient management, outcomes, and satisfaction. Here, we present four Black or Indigenous People of Color who were initially referred for hyperpigmentation, hemihyperplasia, or café au lait spots and found to have syndromic capillary malformations.

Background: Norwegian hospitals have operated within capacity during the COVID-19 pandemic. We present patient and management characteristics, and outcomes for the entire cohort of adult (>18 years) COVID-19 patients admitted to Norwegian intensive care units (ICU) from 10 March to 19 June 2020. Methods: Data were collected from The Norwegian intensive care and pandemic registry (NIPaR). Demographics, co-morbidities, management characteristics and outcomes are described. ICU length of stay (LOS) was analysed with linear regression, and associations between risk factors and mortality were quantified using Cox regression. Results: In total, 217 patients were included. The male to female ratio was 3:1 and the median age was 63 years. A majority (70%) had one or more co-morbidities, most frequently cardiovascular disease (39%), chronic lung disease (22%), diabetes mellitus (20%), and obesity (17%). Most patients were admitted for acute hypoxaemic respiratory failure (AHRF) (91%) and invasive mechanical ventilation (MV) was used in 86%, prone ventilation in 38% and 25% of patients received a tracheostomy. Vasoactive drugs were used in 79% and renal replacement therapy in 15%. Median ICU LOS and time of MV was 14.0 and 12.0 days. At end of follow-up 45 patients (21%) were dead. Age, co-morbidities and severity of illness at admission were predictive of death. Severity of AHRF and male gender were associated with LOS. Conclusions: In this national cohort of COVID-19 patients, mortality was low and attributable to known risk factors. Importantly, prolonged length-of-stay must be taken into account when planning for resource allocation for any next surge. This study was funded by The Norwegian Research Council and Oslo University Hospital.

Background High-grade transformation (HGT) is a rare process whereby conventional low- to intermediate-grade salivary gland carcinomas (SGC) transform into high-grade, poorly or undifferentiated malignancies with focal or complete loss of their conventional histomorphologic features. Because tumors with HGT are associated with a worse prognosis than their conventional counterparts, preoperative recognition of HGT may be of benefit for optimal patient management. Using a multi-institutional approach, we describe the largest fine needle aspiration (FNA) cohort of salivary gland carcinomas with HGT. Methods The archives of 9 large academic medical centers were searched, and 22 cases of SGC with HGT were identified by surgical excision accompanied by preoperative FNA. Clinical and cytomorphologic features were retrospectively reviewed. Results The male-to-female ratio was 14:8, and the mean patient age was 60.2 years. The average tumor size was 3.6 cm, and 19 cases were from the parotid gland. Acinic cell carcinoma with HGT was the most common tumor subtype, comprising 12 cases with HGT, followed by adenoid cystic carcinoma, secretory carcinoma, and other subtypes. Eighteen cases were classified as malignant; however, a specific diagnosis of HGT was not made. Sixteen cases contained a high-grade cytologic component, and 7 cases had a mixture of both conventional and high-grade components retrospectively. Conclusions SGC with HGT should be considered in the differential diagnosis of a salivary gland aspirate exhibiting high-grade cytomorphologic features. The presence of distinct tumor populations, conventional and high-grade, should prompt consideration of HGT, especially when the conventional component is acinic cell carcinoma or adenoid cystic carcinoma.

Background Seasonal influenza causes significant morbidity and mortality and incurs large economic costs. Influenza like illness is a common presenting concern to Emergency Departments (ED), and optimizing the diagnosis of influenza in the ED has the potential to positively affect patient management and outcomes. Therapeutic guidelines have been established to identify which patients most likely will benefit from anti‐viral therapy. Objectives We assessed the impact of rapid influenza PCR testing of ED patients on laboratory result generation and patient management across two influenza seasons. Methods A pre‐post study was performed following a multifaceted clinical redesign including the implementation of rapid influenza PCR at three diverse EDs comparing the 2016‐2017 and 2017‐2018 influenza seasons. Testing parameters including turn‐around‐time and diagnostic efficiency were measured along with rates of bed transfers, hospital‐acquired (HA) influenza, and ED length of stay (LOS). Results More testing of discharged patients was performed in the post‐intervention period, but influenza rates were the same. Identification of influenza‐positive patients was significantly faster, and there was faster and more appropriate prescription of anti‐influenza medication. There were no differences in bed transfer rates or HA influenza, but ED LOS was reduced by 74 minutes following clinical redesign. Conclusions Multifaceted clinical redesign to optimize ED workflow incorporating rapid influenza PCR testing can be successfully deployed across different ED environments. Adoption of rapid influenza PCR can streamline testing and improve antiviral stewardship and ED workflow including reducing LOS. Further study is needed to determine if other outcomes including bed transfers and rates of HA influenza can be affected by improved testing practices.

Aim To explore corticosteroid prescription practices and knowledge among paediatricians. Methods The Paediatricians Corticosteroids Survey, a cross-sectional, web-based survey distributed to Israeli paediatricians between February and July 2018. Results Three hundred and forty-nine paediatricians (105 general paediatricians, 207 subspecialists and 37 paediatric endocrinologists) participated. Two hundred and three (58.2%) had >10 years of paediatric clinical experience and treated >60 patients/wk on average, 175/318 (55%) prescribed corticosteroids to >10% of their patients. On knowledge items, 11/266 (4.1%) responded 'not sure' when tapering of steroids is required, 22/268 (8.2%) to what 'stress dose' meant and 27/268 (10.1%) when a stress dose is required. Multivariate linear analysis showed higher scores were associated with training in paediatric endocrinology (β = 2.271, P = 0.032); medical practice only in a subspecialty (β = 1.909, P = 0.041) or in both general paediatrics and a subspecialty (β = 2.023, P = 0.014), compared to general paediatrics alone and medical studies in Israel (β = 1.059, P = 0.035). Overall, 96.2% thought continued medical education (CME) sessions would be helpful. Conclusion Our findings suggest that despite clinical experience with corticosteroid usage, respondents demonstrated gaps in knowledge for potentially life-threatening situations. Corticosteroid-based CME programs are warranted to improve paediatricians' knowledge and patient management.

Background Molecular testing of thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology is commonly used to guide patient management and is typically performed on freshly collected FNA samples. In this study, the authors evaluated the performance of the ThyroSeq test in cytology smear slides. Methods Air-dried Diff-Quik (DQ)-stained and alcohol-fixed Papanicolaou (Pap)-stained smears were used to determine required cellularity and sensitivity of mutation detection and to compare ThyroSeq v3 Genomic Classifier (GC) results obtained in cytology smears and fresh FNA samples from the same nodules. Results ThyroSeq testing of 31 cytology smears revealed that 25 smears (81%) were adequate for ThyroSeq analysis, including 14 Pap-stained smears (100%) and 11 DQ-stained smears (65%), whereas 6 DQ-stained smears (35%) failed RNA sequencing. The overall accuracy for detecting molecular alterations was 98%, with 100% concordance for mutations and gene expression alterations, 96% concordance for fusions, and 94% concordance for copy number alterations. Cytology smears were adequate for ThyroSeq analysis when at least 200 to 300 cells were present in 1 to 3 slides. ThyroSeq detected all studied mutations down to 5% allele frequency and BRAF mutations down to 1% allele frequency. Testing of smears yielded a positive ThyroSeq GC result in all nodules originally classified as positive. Conclusions Thyroid FNA cytology smear slides with adequate cellularity can be successfully used for ThyroSeq GC testing in approximately 80% of cases, with an even higher success rate in Pap-stained smears. Compared with FNA samples collected into preservative solution, 94% to 100% of different genetic alterations could be accurately detected in smears, validating cytology smears as an alternative for ThyroSeq testing in patients with indeterminate thyroid cytology.

Background Point-of-care ultrasound (POCUS) competence consists of image acquisition, image interpretation, and clinical integration. Limited data exist on POCUS usage patterns and clinical integration by emergency medicine (EM) residents. We sought to determine actual POCUS usage and clinical integration patterns by EM residents and to explore residents' perspectives on POCUS clinical integration. Methods We conducted an explanatory sequential mixed-methods study at a 4-year EM residency program. In phase 1, EM ultrasound (US) attendings observed PGY-4 EM residents' clinical integration of POCUS in real time while on shift in the emergency department (ED). EM US attendings evaluated residents on their intent to perform POCUS, actual POCUS usage, and competence per patient encounter. We used logistic regression to analyze these parameters. In phase 2, we conducted semi-structured interviews with the observed PGY-4 residents regarding POCUS usage and clinical integration in the ED. We analyzed qualitative data for themes. Results Emergency medicine US attendings observed 10 PGY-4 EM residents during 254 high-acuity patient encounters from December 2018 to March 2019. EM US attendings considered POCUS indicated for 26% (66/254) of patients, possibly indicated for 12% (30/254) and not indicated for 62% (158/254). Of the 66 patients for whom EM US attendings considered POCUS indicated, PGY-4s intended to perform POCUS for patient management 61% (40/66) of the time. PGY-4s subsequently incorporated POCUS into patient management 73% (48/66) of the time. EM US attendings considered PGY-4s entrustable to perform POCUS independently 81% (206/254) of the time. We did not find a statistically significant association between shift volume, shift type, or POCUS application, and resident intent to perform POCUS nor competence. Interviews identified three factors that influence PGY-4's POCUS clinical integration: motivations to use POCUS, barriers to utilization, and POCUS educational methods. Conclusions This mixed-methods study identified a significant gap in POCUS utilization and clinical integration by PGY-4 EM residents for clinically indicated cases identified by EM US attendings. As clinical integration is a cornerstone of POCUS competence, it is important to ensure that EM resident POCUS curricula emphasize training on clinical utilization and indications for POCUS while on shift in the ED.

SARS‐CoV‐2, the cause of the COVID‐19 pandemic has significantly impacted cardiovascular healthcare. Patients with pre‐existing cardiovascular disease are at higher risk of morbidity and mortality. The virus may affect the heart directly and indirectly with clinical syndromes of acute myocardial injury, myocarditis, acute coronary syndromes, heart failure, arrhythmias, and venous thromboembolism. Some therapeutics under investigation for COVID‐19 may also have adverse cardiac effects. The involvement of the RAAS system in viral entry makes it pertinent to consider the effects of medications that modulate the system. Comprehensive knowledge of peculiar cardiovascular manifestations of COVID‐19 and the role of RAAS in the prognosis of COVID‐19 disease is needed for optimal patient management.

Coronavirus disease 2019 (COVID-19) is spreading worldwide, and has been declared as an international public health concern. Patients with lung cancer are highly susceptible to infection compared to healthy individuals because of systemic immunosuppression induced by malignancy and anticancer therapy. Furthermore, patients with cancer demonstrate poorer outcomes following infection. Hence, patients with lung cancer should be considered a priority group for COVID-19 prevention. Furthermore, the routine treatment of patients with cancer has been affected during the COVID-19 pandemic, and patients may not have been able to undergo timely and effective antitumor treatment, thereby indicating a poor prognosis. Here, we provide some suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer who have fever and respiratory symptoms. Our medical team also provide clinical recommendations on lung cancer management during the COVID-19 pandemic, for carrying out meticulous and individualized clinical management of lung cancer patients and maximum protection to effectively prevent COVID-19. KEY POINTS: Significant findings of the study This article provides suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer with fever and respiratory symptoms. What this study adds This article makes clinical recommendations on lung cancer management during the COVID-19 pandemic.

Background Infection is a well‐recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter‐defibrillator (S‐ICD). Although the AHA/ACC/HRS guidelines include recommendations for S‐ICD use, currently there are no clinical trial data that address the diagnosis and management of S‐ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods A process mapping methodology was used to achieve a primary goal – the development of consensus on the diagnosis and management of S‐ICD infections. Two face‐to‐face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S‐ICD infections. Results Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. Conclusion Achieving expert panel consensus by process mapping methodology in S‐ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management.

Magnetic resonance lymphangiography (MRL) is a noninvasive imaging technique that can be used in the management of lymphatic disorders to delineate the central lymphatic system for treatment planning. This article reviews the MRL technique, its advantages, limitations, indications, and impact on patient management. Level of Evidence 5 Technical Efficacy Stage 3 J. MAGN. RESON. IMAGING 2021;53:374-380.

The Fontan operation remains the final palliation for thousands of patients with complex congenital heart disease. By creating a Fontan circuit, control of cardiac output and congestion is wrested away from the ventricle and new haemodynamic forces take control. Understanding how to control the flow in the Fontan circuit will enable clinicians to improve patient management and possibly prevent future complications. CONCLUSION: This review proposes a framework of principles to conceptualise the functionality and limitations of a Fontan circulation. ispartof: ACTA PAEDIATRICA vol:109 issue:4 pages:651-658 ispartof: location:Norway status: published

Misdirection of nasogastric tubes into the cranial cavity of trauma patients is a well‐understood complication that has been well documented in the literature. As a result, recommendations have been established in the use of nasogastric tubes where trauma or suspected skull fractures are identified. Orogastric tube placement is also a commonly performed procedure during trauma resuscitation attempts and is often necessary during patient management. However, no literature currently exists demonstrating misdirection of orogastric tube placement into the spinal canal following trauma and as such, no similar recommendations exist. We review a case of orogastric tube misplacement into the spinal canal due to atlanto‐occipital dissociation and suggest a recommendation for prevention.

Burn injury results in a sustained hypermetabolic state with resulting increased caloric and protein requirements to support the stress and immune responses; augmented protein, fat, and carbohydrate catabolism; oxidative stress; and exudative losses. Along with surgical debridement, nutrition and resuscitation are the foundations of patient management after severe burn injury. Recent literature has demonstrated a clear benefit to early enteral nutrition initiation during the resuscitation period. This review aims to examine recent literature discussing both physiologic impact of burn injury and approaches to feeding during resuscitation after burn injury; including methods of determining nutrition requirements, routes, timing, and monitoring response and the associated benefits and consequences thereof.

BACKGROUND: The use of an indwelling peritoneal catheter system in hospitalized patients with ascites could facilitate patient management by the prevention of repetitive abdominal paracentesis. Despite these possible benefits, the use of indwelling catheters is not widely established. OBJECTIVE: This retrospective study aimed to evaluate the feasibility, effectiveness and safety of the use of an indwelling catheter for ascites drainage in the clinical routine. METHODS: This retrospective study included all indwelling peritoneal catheter placements in our department in hospitalized patients with cirrhosis between 2014 and 2017. RESULTS: A total of 324 indwelling catheter placements for ascites in 192 hospitalized patients with cirrhosis were included. The catheter (7F, 8 cm) was placed ultrasound-assisted bed-side on the hospital ward. The technical success rate of the catheter placement was 99.7% (323/324). In 17.5% (64/324) the catheter was placed to optimize ascitic drainage prior to an abdominal intervention (e.g. transjugular intrahepatic portosystemic shunt). The median time of catheter retention was 48 hours (8–168 hours) and the median cumulative amount of drained ascites 8000 ml (550–28,000). The most common adverse event was acute kidney injury (49/324, 15.1%); the risk was particularly higher in patients with a Model for End-Stage Liver Disease (MELD) score ≥ 16 (p = 0.028; odds ratio 2.039). Ascitic fistula after catheter removal was observed in 9.6% (31/324). Catheter-related infections occurred in 4.3% (14/324), and bleeding was documented in three cases (0.8%) with one major bleeding (0.3%). CONCLUSION: The placement of an indwelling catheter for repetitive ascitic drainage in hospitalized patients with cirrhosis can be established in the clinical routine, facilitating patient management. High-MELD patients especially have to be monitored for acute kidney injury.

For millions of years, microbiota residing within us, including those in the oral cavity, coexisted in a harmonious symbiotic fashion that provided a quintessential foundation for human health. It is now clear that disruption of such a healthy relationship leading to microbial dysbiosis causes a wide array of infections, ranging from localized, mild, superficial infections to deep, disseminated life-threatening diseases. With recent advances in research, diagnostics, and improved surveillance we are witnessing an array of emerging and re-emerging oral infections and orofacial manifestations of systemic infections. Orofacial infections may cause significant discomfort to the patients and unnecessary economic burden. Thus, the early recognition of such infections is paramount for holistic patient management, and oral clinicians have a critical role in recognizing, diagnosing, managing, and preventing either new or old orofacial infections. This paper aims to provide an update on current understanding of well-established and emerging viral, bacterial, and fungal infections manifesting in the human oral cavity.

There are approximately 7,000 rare diseases affecting 25–30 million Americans, with 80% estimated to have a genetic basis. This presents a challenge for genetics practitioners to determine appropriate testing, make accurate diagnoses, and conduct up-to-date patient management. Exome sequencing is a comprehensive diagnostic approach, but only 25–41% of patients receive a molecular diagnosis. The remaining three-fifths to three-quarters of patients undergoing exome sequencing remain undiagnosed. The Stanford Center for Undiagnosed Diseases (CUD), a clinical site of the Undiagnosed Diseases Network, evaluates patients with undiagnosed and rare diseases using a combination of methods including exome sequencing. Frequently these patients have non-diagnostic exome sequencing results, but strategic follow up techniques identify diagnoses in a subset. We present techniques used at the CUD that can be adopted by genetics providers in clinical follow-up of cases where exome sequencing is non-diagnostic. Solved case examples illustrate different types of non-diagnostic results and the additional techniques that led to a diagnosis. Frequent approaches include segregation analysis, data reanalysis, genome sequencing, additional variant identification, careful phenotype-disease correlation, confirmatory testing, and case matching. We also discuss prioritization of cases for additional analyses.

Small cell carcinoma of the ovary (SCCO) is an exceedingly rare malignant neoplasm. It has been classified into two types: hypercalcemic and pulmonary type, the former being relatively more common. These are highly aggressive neoplasms with rapid down-hill course and poor disease-outcome. A high index of clinical suspicion, systematic radiological evaluation, and an early tissue diagnosis are a must for timely patient management and a better outcome. A definitive diagnosis can be established by demonstration of the characteristic morphologic and immunochemical features. We report a case of SCCO of pulmonary type in a peri-menopausal female, presenting with a large abdomino-pelvic mass, which was diagnosed by fine needle aspiration cytology (FNAC), by immunocytochemistry on cell-block. In addition, cytological features of metastatic SCCO, pulmonary type, in the Papanicolaou stained liquid-based cytology (SurePath) preparation are also presented. The current report highlights the diagnostic utility of FNAC in the diagnosis of such rare gynecological malignancies.

Background The aim of the present study was to integrate available data published in the literature on extracapsular invasion in cases of CXPA that correlated findings with the prognosis of analysed patients. Methods An electronic search was carried out at the MEDLINE/PubMed, EMBASE and Cochrane Collaboration Library databases. Articles that assessed the relationship between extracapsular invasion and survival of patients diagnosed with CXPA were selected for the systematic review. Quality assessment was performed, in duplicate, for each eligible study by independent reviewers who used the operationalized prognostic biomarker reporting the REMARK guidelines. Results Eight published articles met all the inclusion criteria and were selected. Extracapsular invasion was evaluated in all selected studies and was correlated with clinical and pathological parameters. Recurrence and death due to the neoplastic process became a frequent finding in cases of tumours with extracapsular invasion >1.5 mm, being an important cut-off point in the prognostic analysis of cases diagnosed as CXPA. Conclusions This systematic review demonstrates the importance of evaluating extracapsular invasion in cases diagnosed as CXPA, considering that tumours with invasion >1.5 mm, regardless of histopathological subtype, are associated with a worse prognosis. It is important to analyse the extracapsular invasion, especially as an auxiliary method to assess the prognosis of cases diagnosed in the initial clinical stages, thus identifying the possible biological behaviour of the neoplastic process and guiding the most appropriate patient management.

Background Cardiac resynchronization therapy (CRT) has been shown to improve morbidity and mortality for heart failure (HF) patients. Little is known about the trends in CRT use and outcomes of these patients in New Zealand. Method Mortality, hospitalization events and complications in HF patients in the Northern Region of New Zealand implanted with CRT devices from Jan‐2007 to June‐2015 were reviewed. Results Two‐hundred patients underwent CRT implantation during the study period. There was a gradual increase in CRT‐D implantation (n = 157) but the number remained static for CRT‐P (n = 43). Patients who received CRT‐P were older (mean age 65.9 ± 14.0 years vs 61.5 ± 10.2 years, P

Whole exome sequencing (WES) is expected to impact patient management, but data surrounding the types of downstream effects and how frequently these effects are observed depending on the type of WES results received is limited. This study investigated changes to medical management and genetic counseling (GC) options following WES for individuals with positive and negative results. Electronic medical records of patients who had positive (n = 37) or negative (n = 41) WES results from Cincinnati Children's Hospital were retrospectively reviewed. Pre- and post-WES management and GC options were analyzed as were differences between positive and negative results. Almost all participants (97%) were observed to have at least one difference in medical management and/or GC options following WES. Comparing pre- and post-WES detected significant differences (p ≤ 0.05) in genetic testing, imaging, and metabolic testing regardless of WES results. Participants with positive results also had significant differences in recurrence risk, reproductive options, testing for family members, and support groups. Pre- to post-WES differences were significantly different between participants with positive and negative results in specialist referrals, lifestyle recommendations, recurrence risk, and all GC options (p ≤ 0.05); specifically, participants with positive results were more likely to have differences in these categories. Overall, differences in medical management and/or GC options were observed for participants with both types of WES results (positive and negative). Results from this study may contribute to the understanding of how WES impacts patients and their care and thus improve its utilization.

Introduction The study objective was to build a machine learning model to predict incident mild cognitive impairment, Alzheimer's Disease, and related dementias from structured data using administrative and electronic health record sources. Methods A cohort of patients (n = 121,907) and controls (n = 5,307,045) was created for modeling using data within 2 years of patient's incident diagnosis date. Additional cohorts 3–8 years removed from index data are used for prediction. Training cohorts were matched on age, gender, index year, and utilization, and fit with a gradient boosting machine, lightGBM. Results Incident 2-year model quality on a held-out test set had a sensitivity of 47% and area-under-the-curve of 87%. In the 3-year model, the learned labels achieved 24% (71%), which dropped to 15% (72%) in year 8. Discussion The ability of the model to discriminate incident cases of dementia implies that it can be a worthwhile tool to screen patients for trial recruitment and patient management.

We here describe the development of an evidence-based cancer dataset by an International Collaboration on Cancer Reporting expert panel for the reporting of primary testicular neoplasia, and present the 'required' and 'recommended' elements to be included in the pathology report, as well as a commentary. This dataset encompasses the updated 2016 World Health Organisation classification of urological tumours, the results of an International Society of Urological Pathology consultation, and also staging with our preferred method: the American Joint Committee on Cancer version 8. Implementation of this dataset will facilitate consistent and accurate data collection between different cohorts, facilitate research, and hopefully result in improved patient management.

De novo variants in the WDR26 gene leading to haploinsufficiency have recently been associated with Skraban-Deardorff syndrome. This condition is an ultra-rare autosomal dominant neurodevelopmental disorder characterized by a broad range of clinical signs, including intellectual disability (ID), developmental delay (DD), seizures, abnormal facial features, feeding difficulties, and minor skeletal anomalies. Currently, 18 cases have been reported in the literature and for only 15 of them a clinical description is available. Here, we describe a child with Skraban-Deardorff syndrome associated with the WDR26 pathogenic de novo variant NM_025160.6:c.69dupC, p.(Gly24ArgfsTer48), and an adult associated with the pathogenic de novo variant c.1076G > A, p.(Trp359Ter). The adult patient was a 29-year-old female with detailed information on clinical history and pharmacological treatments since birth, providing an opportunity to map disease progression and patient management. By comparing our cases with published reports of Skraban-Deardorff syndrome, we provide a genetic and clinical summary of this ultrarare condition, describe the clinical management from childhood to adult age, and further expand on the clinical phenotype.

Background Endoscopically defined mucosal healing in Crohn's disease is associated with improved outcomes. Panenteric capsule endoscopy enables a single non‐invasive assessment of small and large bowel mucosal inflammation. Aims and Methods This multicentre observational study of patients with suspected and established Crohn's disease examined the feasibility, safety and impact on patient outcomes of panenteric capsule endoscopy in routine clinical practice. The potential role in assessment of disease severity and extent by a comparison with existing clinical and biochemical markers is examined. Results Panenteric capsule endoscopy was performed on 93 patients (71 with established and 22 with suspected Crohn's disease). A complete examination occurred in 85% (79/93). Two cases (2.8%) of capsule retention occurred in patients with established Crohn's disease. Panenteric capsule resulted in management change in 38.7% (36/93) patients, including 64.6% (32/48) of those with an established diagnosis whose disease was active, and all three patients with newly diagnosed Crohn's disease. Montreal classification was upstaged in 33.8% of patients with established Crohn's disease and mucosal healing was demonstrated in 15.5%. Proximal small bowel disease upstaged disease in 12.7% and predicted escalation of therapy (odds ratio 40.3, 95% confidence interval 3.6–450.2). Raised C‐reactive protein and faecal calprotectin were poorly sensitive in detecting active disease (0.48 and 0.59 respectively). Conclusions Panenteric capsule endoscopy was feasible in routine practice and the ability to detect proximal small bowel disease may allow better estimation of prognosis and guide treatment intensification. Panenteric capsule endoscopy may be a suitable non‐invasive endoscopic investigation in determining disease activity and supporting management decisions., Key Summary Summarise the established knowledge on this subject Biochemical and clinical markers poorly predict active disease and need for treatment escalation;Panenteric capsule endoscope is feasible, safe and has the potential to non‐invasively assess patients with Crohn's Disease. What are the significant and/or new findings of this study? Panenteric capsule endoscope can upstage disease in one‐third of patients with a threefold increase in the identification of proximal small bowel disease;Identification of proximal small bowel disease predicted treatment intensification.

Whilst urgent gynecological and oncologic operations have continued, the SARS-CoV-2 (COVID-19) pandemic has impacted patient management through postponement of elective surgeries.[1-5] Cohen et al.[6] suggested that during the pandemic each patient should be evaluated individually with added measures for the protection of both the patient and healthcare professionals. Therefore, we conducted a study evaluating patients' and hospital workers' health status during the pandemic in Turkey.

Introduction For the EARs NOSE AND THROAT (ENT) surgeon, there are many challenges that show‐up in the clinical management of a patient affected by a head and neck cancer during COVID‐19 pandemic, especially in the postoperative period. Methods During the acute COVID‐19 emergency phase in Italy, we analyzed the management of a patient affected by a head and neck cancer. We reported several clinical data about the hospitalization period, pointing out the difficulties encountered both from clinical and management point of view. Results During pandemic, we admitted 27 oncological patients at our ENT Department. Delays in surgical procedures, complications of hospitalizations, need for radiological studies, and possible transfer to other hospital ward, due to suspect SARS‐CoV‐2 infection, were registered. Conclusions The changes in the whole health care system during the COVID‐19 pandemic have impacted the management of patients with head and neck cancer, generating several clinical challenges for the ENT surgeon.