KRAS G12D mutation in Brunner gland adenoma.

Brunner gland lesions (BGLs) encompass benign proliferations of the homonymous glands and have been designated as hyperplasia, adenoma (BGA), hamartoma or nodule. In general terms, lesions larger than 0.5 cm are considered true neoplasia with unknown malignant potential and unclear pathogenesis. Genetic alterations have seldom been reported in BGL, and include SMAD4/DPC4 and LRIG1, but not KRAS (Kirsten rat sarcoma viral oncogene homologue) to the best of our knowledge.We present the case of a man in his 60s, evaluated for iron deficiency anaemia harbouring a 1.5 cm BGA found by duodenoscopy. Immunohistochemistry failed to reveal microsatellite instability, and next-generation sequencing revealed a KRAS G12D point mutation.

Performance comparison of reusable versus disposable colonoscopes:a non-inferiority Trial (preprint)

Objective We herein compared the performance of reusable and disposable colonoscopes in patients scheduled to undergo colonoscopy with a view of preventing patient cross-infection, protecting the safety of clinical medical staff, reducing the risk of infection, and minimizing the decontamination process, particularly during the coronavirus disease 2019 pandemic. Methods We randomly divided patients meeting the enrollment criteria into reusable and disposable colonoscopy groups; the success rate of photographing customary anatomical sites with a non-inferiority margin of -8% was the primary endpoint. Secondary endpoints were the adenoma detection rate, operation time, endoscopic image quality score, endoscopic mucosal resection (EMR) success rate, and adverse events. Results We recruited patients who were treated using reusable or disposable (n = 45, each) colonoscopes. Both groups had 100% success rate for capturing images of customary anatomical sites, with no between-group differences. The lower limit of 95% CI was - 7.8654%, which was greater than the non-inferiority threshold of -8%. The disposable group had a significantly lower average image quality score (26.09 ±1.33 vs. 27.44±0.59, P < 0.001) than the reusable group. The groups did not significantly differ in maneuverability, safety, or device failure/defect rate. The en-bloc EMR success rate was 100% in both groups. EMR took significantly longer in the disposable group (466.18 s±180.56 s vs . 206.32 s±109.54 s, P < 0.001). The incidence of EMR-related bleeding and perforation did not significantly differ between the groups. Conclusions Disposable colonoscope endoscopy is safe and feasible for endoscopy examinations and EMR.

Modeling analysis of COVID 19-related delays in colorectal cancer screening on simulated clinical outcomes (preprint)

Objective: Colorectal cancer (CRC) screening disruptions observed during the COVID-19 pandemic put patients at risk for more advanced-stage disease when diagnosed. This budget impact simulation model assessed increased use of multi-target stool DNA [mt-sDNA] or fecal immunochemical [FIT] tests to offset disruption in colonoscopy screening due to COVID-19 in adults at average-risk for CRC, from a United States payer perspective Main outcomes and measures: Compared to the base case (S0; 85% colonoscopy and 15% non-invasive tests), the estimated number of missed CRCs and advanced adenomas (AAs) were determined for four COVID-19-affected screening scenarios: S1, 9 months of CRC screening at 50% capacity, followed by 21 months at 75% capacity; S2, S1 followed by increasing stool-based testing by an average of 10% over 3-years; S3, 18 months of CRC screening at 50% capacity, followed by 12 months of 75% capacity; and S4, S3 followed by increasing stool-based testing by an average of 13% over 3-years. Results: Increasing the proportional use of mt-sDNA improved AA detection by 6.0% (Scenario 2 versus 1) to 8.4% (Scenario 4 versus 3) and decreased the number of missed CRCs by 15.1% to 17.3%, respectively. Increasing FIT utilization improved the detection of AAs by 3.3% (Scenario 2 versus 1) to 4.6% (Scenario 4 versus 3) and decreased the number of missed CRCs by 12.9% to 14.9%, respectively. Across all scenarios, the number of AAs detected was higher for mt-sDNA than for FIT, and the number of missed CRCs was lower for mt-sDNA than for FIT. Conclusions and relevance: Using home-based stool tests for average-risk CRC screening can mitigate the consequences of reduced colonoscopy screening resulting from the COVID-19 pandemic. Use of mt-sDNA led to fewer missed CRCs and more AAs detected, compared to FIT.

Treatment of Cushing's syndrome with osilodrostat: practical applications of recent studies with case examples.

Endogenous Cushing's syndrome (CS) is a rare endocrine condition frequently caused by a tumor resulting in elevated cortisol levels. Cushing's disease (CD) caused by an adrenocorticotropic hormone-secreting pituitary adenoma is the most common form of endogenous CS. Medical therapy for CD is mostly used as second-line treatment after failed surgery or recurrence and comprises several pituitary-directed drugs, adrenal steroidogenesis inhibitors, and a glucocorticoid receptor blocker, some of which are US Food and Drug Administration (FDA)-approved for this condition. The recent Pituitary Society consensus guidelines for diagnosis and management of CD described osilodrostat, an oral inhibitor of 11ß-hydroxylase, as an effective, FDA-approved medical therapy for CD. Because clinical experience outside clinical trials is limited, we provide here a review of published data about osilodrostat and offer example case studies demonstrating practical considerations on the use of this medication. Recommendations regarding osilodrostat are provided for the following situations: specific assessments needed before treatment initiation; monitoring for adrenal insufficiency, hypokalemia, and changes in QTc; the potential value of a slow up-titration in patients with mild disease; managing temporary treatment cessation for patients with CD who have acquired coronavirus disease 2019; monitoring for increased testosterone levels in women; exercising caution with concomitant medication use; considering whether a higher dose at nighttime might be beneficial; and managing cortisol excess in ectopic and adrenal CS. This review highlights key clinical situations that physicians may encounter when using osilodrostat and provides practical recommendations for optimal patient care when treating CS, with a focus on CD.

A Novel Convolutional Neural Network Model as an Alternative Approach to Bowel Preparation Evaluation Before Colonoscopy in the COVID-19 Era: A Multicenter, Single-Blinded, Randomized Study.

INTRODUCTION: Adequate bowel preparation is key to a successful colonoscopy, which is necessary for detecting adenomas and preventing colorectal cancer. We developed an artificial intelligence (AI) platform using a convolutional neural network (CNN) model (AI-CNN model) to evaluate the quality of bowel preparation before colonoscopy. METHODS: This was a colonoscopist-blinded, randomized study. Enrolled patients were randomized into an experimental group, in which our AI-CNN model was used to evaluate the quality of bowel preparation (AI-CNN group), or a control group, which performed self-evaluation per routine practice (control group). The primary outcome was the consistency (homogeneity) between the results of the 2 methods. The secondary outcomes included the quality of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), polyp detection rate, and adenoma detection rate. RESULTS: A total of 1,434 patients were enrolled (AI-CNN, n = 730; control, n = 704). No significant difference was observed between the evaluation results ("pass" or "not pass") of the groups in the adequacy of bowel preparation as represented by BBPS scores. The mean BBPS scores, polyp detection rate, and adenoma detection rate were similar between the groups. These results indicated that the AI-CNN model and routine practice were generally consistent in the evaluation of bowel preparation quality. However, the mean BBPS score of patients with "pass" results were significantly higher in the AI-CNN group than in the control group, indicating that the AI-CNN model may further improve the quality of bowel preparation in patients exhibiting adequate bowel preparation. DISCUSSION: The novel AI-CNN model, which demonstrated comparable outcomes to the routine practice, may serve as an alternative approach for evaluating bowel preparation quality before colonoscopy.

Impact of changes to the interscreening interval and faecal immunochemical test threshold in the national bowel cancer screening programme in England: results from the FIT pilot study.

INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold. METHODS: We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 individuals aged 59-75, screened for colorectal cancer (CRC) using FIT. We estimated screening sensitivity to CRC, adenomas, advanced adenomas (AA) and mean sojourn time of each pathology by faecal haemoglobin (f-Hb) thresholds, then predicted the detection of these abnormalities by interscreening interval and f-Hb threshold. RESULTS: Current 2-yearly screening with a f-Hb threshold of 120 µg/g was estimated to generate 16,092 colonoscopies, prevent 186 CRCs, detect 1142 CRCs, 7086 adenomas and 4259 AAs per 100,000 screened over 15 years. A higher threshold at 180 µg/g would reduce required colonoscopies to 11,500, prevent 131 CRCs, detect 1077 CRCs, 4961 adenomas and 3184 AAs. A longer interscreening interval of 3 years would reduce required colonoscopies to 10,283, prevent 126 and detect 909 CRCs, 4796 adenomas and 2986 AAs. CONCLUSION: Increasing the f-Hb threshold was estimated to be more efficient than increasing the interscreening interval regarding overall colonoscopies per screen-benefited cancer. Increasing the interval was more efficient regarding colonoscopies per cancer prevented.

Microbial Risk Score for Capturing Microbial Characteristics, Integrating Multi-omics Data, and Predicting Disease Risk (preprint)

Background With the rapid accumulation of microbiome-wide association studies, a great amount of microbiome data are available to study the microbiome’s role in human disease and advance the microbiome’s potential use for disease prediction. However, the unique features of microbiome data hinder its utility for disease prediction. Methods Motivated from the polygenic risk score framework, we propose a microbial risk score (MRS) framework to aggregate the complicated microbial profile into a summarized risk score that can be used to measure and predict disease susceptibility. Specifically, the MRS algorithm involves two steps: 1) identifying a sub-community consisting of the signature microbial taxa associated with disease, and 2) integrating the identified microbial taxa into a continuous score. The first step is carried out using the existing sophisticated microbial association tests and pruning and thresholding method in the discovery samples. The second step constructs a community-based MRS by calculating alpha diversity on the identified sub-community in the validation samples. Moreover, we propose a multi-omics data integration method by jointly modeling the proposed MRS and other risk scores constructed from other omics data in disease prediction. Results Through three comprehensive real data analyses using the NYU Langone Health COVID-19 cohort, the gut microbiome health index (GMHI) multi-study cohort, and a large type 1 diabetes cohort separately, we exhibit and evaluate the utility of the proposed MRS framework for disease prediction and multi-omics data integration. In addition, the disease-specific MRSs for colorectal adenoma, colorectal cancer, Crohn’s disease, and rheumatoid arthritis based on the relative abundances of 5, 6, 12, and 6 microbial taxa respectively are created and validated using the GMHI multi-study cohort. Especially, Crohn’s disease MRS achieves AUCs of 0.88 ([0.85-0.91]) and 0.86 ([0.78-0.95]) in the discovery and validation cohorts, respectively. Conclusions The proposed MRS framework sheds light on the utility of the microbiome data for disease prediction and multi-omics integration, and provides great potential in understanding the microbiome’s role in disease diagnosis and prognosis.

The impact of delaying colonoscopies during the COVID-19 pandemic on colorectal cancer detection and prevention.

PURPOSE: The COVID-19 pandemic resulted in a partial to total shutdown of endoscopy in many healthcare centers. This study aims to quantify the impact of the reduction in colonoscopies on colorectal cancer (CRC) detection and screening. METHODS: After institutional ethics board approval, the endoscopy database at an academic tertiary-care center in Montreal, Canada, was searched for all colonoscopies performed from during the first wave locally (March-June 2020), and during the ramp up period where endoscopy service resumed (July to August 2020). We compared these periods to the same periods in 2019, the pre-pandemic periods. The indications, CRC and adenoma detection rates, as well as the prioritization of urgent procedures were compared. RESULTS: In the first wave, only 462 colonoscopies were performed, compared to 2515 in the same period in 2019, an 82% reduction. The ramp up period saw 843 colonoscopies performed compared to 1328 in 2019, a 35% reduction. Urgent and inpatient colonoscopies numbers increased (324 (24.8%) vs. 220 (5.7%)) while surveillance and high-risk screening colonoscopies fell (376 (28.8%) vs 1869 (48.6%)). Emergency access to colonoscopy was preserved with a median time to endoscopy of < 1 day (IQR 0,1) in both pandemic periods. During the pandemic periods, there was an absolute reduction in CRC diagnosis of 28, despite the CRC detection per colonoscopy rate increasing slightly in the first wave from 1.7% (44) to 3.9% (18), and in the ramp up period from 2.5% (33) to 3.6% (31). The rate of adenoma detection per colonoscopy did not increase significantly between the pre- and pandemic periods, resulting in reduction in adenoma removal in 723 patients. DISCUSSION: The restriction of access to colonoscopy resulted in a significant reduction in screening and surveillance of high-risk patients, adenomas removed, and CRCs diagnosed. Clinicians and patients will face the oncologic ramifications this the coming years.

The Impact of Face Shields on the Quality of Colonoscopy During the COVID-19 Pandemic (preprint)

Background: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Healthcare workers are at a higher risk for exposure to COVID-19 infection than the general population. During the COVID-19 pandemic, endoscopists are recommended to wear personal protective equipment (PPE), including face shields, to prevent COVID-19 transmission. However, to the best of our knowledge, there are no reports on the impact of face shields on the quality of colonoscopy. This study aimed to determine whether the use of PPE, including face shields, affects the quality of colonoscopy during the COVID-19 pandemic. Methods: We retrospectively reviewed the medical records of patients who underwent screening or surveillance colonoscopy performed at Dong-A University Hospital between June 2020 and March 2021 during the COVID-19 pandemic. Endoscopists wore isolation gowns, disposable gloves, and KF94 masks from June 2020 to October 2020. From November 2020, endoscopists additionally wore face shields. Therefore, we compared the colonoscopy quality indicators during the 5 months without the use of face shields and the 5 months with the use of face shields. We calculated the overall adenoma detection rates (ADRs) of the group using face shields and the group not using face shields. Further, the polyp detection rate (PDR), sessile serrated lesion detection rate (SSLDR), advanced neoplasia detection rate (ANDR), polyp per colonoscopy, and adenoma per colonoscopy were calculated for each group. Results: : In total, 1,359 patients were included in the study; the face shield and non-face shield groups comprised 679 and 680 patients, respectively. We found no statistically significant differences in the PDR (49.04 vs. 52.50%, p =0.202), ADR (38.59 vs. 38.97%, p =0.884) SSPDR (1.91 vs. 1.32%, p =0.388), and ANDR (3.98 vs. 3.97%, p =0.991) between the groups. In both the experienced endoscopist group and trainee endoscopist group, there was no difference in the colonoscopy quality indicators between the groups of patients examined by endoscopists with and without face shields. Conclusions: : The quality indicators of colonoscopy were not affected by face shields during the COVID-19 pandemic.

Effect of using personal protective equipment during the COVID-19 pandemic on the quality indicators of screening colonoscopies (preprint)

Background Coronavirus Disease 2019 (COVID-19) has affected many facets of the practice of medicine including screening colonoscopies. Aims Our study looks to observe if there has been an effect on the quality of colonoscopies, as indicated by quality measures such as cecal intubation rate (CIR), cecal intubation time (CIT), scope withdrawal time (SWT) and adenoma detection rate (ADR) with the adoption of standard COVID-19 precautions. Methods We conducted a retrospective chart review to analyze the effects of the COVID-19 pandemic on screening colonoscopies. The study utilized data on CIR, CIT, SWT and ADR from outpatient, non-emergent procedures conducted at 3 endoscopy suites of St Luke’s University Health Network. All inpatient and emergent procedures were excluded. Results Our study demonstrated that the total number of screening colonoscopies was decreased between 2019 to 2020 (318 in 2019 vs 157 in 2020, p= 0.005). CIT (320±105 seconds in 2019 vs 392±107 seconds in 2020, p=0.001) and SWT (706±232 seconds in 2019 vs 830±241 seconds in 2020, p=0.001) were increased while CIR (98.2% in 2019 vs 96.6% in 2020, p=0.04) was decreased between 2019 and 2020 likely due to PPE introduction. ADR was similar between the two groups (38.23 (12.50-66.66) in 2019 vs 38.18(16.66-66.00) in 2020, p=0.8). Conclusion Our study showed that quality indices for screening colonoscopies like CIR, CIT, and SWT were negatively impacted during the COVID-19 time period. ADR, however, were similar. Thus, the efficiency of the procedures was affected by the use of PPE but it did not affect the colonoscopy’s clinical benefit.

Coronavirus Disease 2019 (Covid-19) Outbreak and Pituitary Apoplexy (preprint)

Background. Pituitary apoplexy (PA) is a rare and potentially life-threatening condition characterized by pituitary hemorrhage, often in the setting of a preexisting pituitary adenoma. Risk factors and mechanisms associated to PA are poorly understood. Although involvement of the nervous system in SARS-CoV-2 infection causing intracranial hemorrhagic complications has been documented, the association between COVID-19 infection and PA has yet to be determined.Methods . From a prospectively collected database of patients with pituitary adenomas, we retrospectively reviewed the electronical medical records and scans of patients with pituitary apoplexy during the COVID-19 outbreak, since March 2020 to December 2020, that were treated at a tertiary care center.Results. Herein, we report three consecutive cases of patients with PA and concomitant COVID-19 infection. Most common symptom at presentation was headache and visual worsening. Included patients were successfully treated with surgical decompression and medical management of the hormonal deficits, experiencing moderate to significant improvement of their visual symptoms at last follow up. COVID-19 infection in the perioperative period was corroborated throughout polymerase chain reaction testing in all patients.Conclusions. COVID-19 positive patients may be at an increased risk of developing PA. Angiotensin-converting enzyme 2 receptors expressed in cerebrovascular endothelium may potentially play a role in the molecular mechanisms that induce changes of the vascular autoregulation and cerebral blood flow and predispose to pituitary hemorrhage in patients harboring a pituitary adenoma.

A Potential Impact of SARS-CoV-2 on Pituitary Glands and Pituitary Neuroendocrine Tumors (preprint)

Introduction: Angiotensin-converting enzyme 2 (ACE2) is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effects of SARS-CoV-2 on normal pituitary glands function or pituitary neuroendocrine tumors (PitNETs) have not yet been elucidated. Thus, the present study aimed to investigate the potential risks of SARS-CoV-2 infection on the impairment of pituitary glands and the development of PitNETs.Methods: PitNETs tissues were obtained from 114 patients, and normal pituitary gland tissues were obtained from the autopsy. The mRNA levels of ACE2 and angiotensin II receptor type 1 (AGTR1) were examined by quantitative real-time PCR. Immunohistochemical staining was performed for ACE2 in 69 PitNETs and 3 normal pituitary glands. The primary tumor cells and pituitary cell lines (MMQ, GH3 and AtT-20/D16v-F2) were treated with diminazene aceturate (DIZE), an ACE2 agonist, with various dose regimens. The pituitary hormones between 43 patients with SARS-CoV-2 infection were compared with 45 healthy controls.Results: Pituitary glands and the majority of PitNET tissues showed low/negative ACE2 expression at both the mRNA and protein levels, while AGTR1 showed high expression in normal pituitary and corticotroph adenomas. ACE2 agonist increased the secretion of ACTH in AtT-20/D16v-F2 cells through downregulating AGTR1. The level of serum adrenocorticotropic hormone (ACTH) was significantly increased in COVID-19 patients as compared to normal controls (p<0.001), but was dramatically decreased in critical cases as compared to non-critical patients (p=0.003).Conclusion: This study revealed a potential impact of SARS-CoV-2 infection on corticotroph cells and adenomas.

Pituitary surgery during Covid-19: a first hand experience and evaluation.

PURPOSE: During the Covid-19 pandemic every hospital has had to change its internal organization. Different institutions have highlighted the risks connected with endoscopic endonasal surgery. The goal of this paper is to illustrate the feasibility of pituitary region surgery during the SARS-CoV-2 pandemic. METHODS: After two negative Covid tests were obtained, three patients with macro GH-secreting tumors, and two patients with micro ACTH-secreting tumors resistant to medical treatment underwent surgery during the pandemic. During the surgery, every patient was treated as if they were positive. RESULTS: Neither operator, nor patient have developed Covid symptoms. The two neurosurgeons performing the operations underwent two Covid swab, which resulted negative. CONCLUSIONS: Pituitary surgery is a high risk non-urgent surgery. However, the method described has so far been effective and is safe for both patients and healthcare providers.

Diagnostic accuracy of Faecal Immunochemical Testing for patients with symptoms of colorectal cancer: a retrospective cohort study of 14,487 consecutive test requests from English primary care (preprint)

Objective To ascertain the diagnostic performance of faecal immunochemical test (FIT) in symptomatic primary care patients, to provide objective data on which to base referral guidelines. Design Stool samples from routine primary care practice in Oxfordshire, UK were analysed using the HM-JACKarc FIT method between March 2017 to March 2020. Clinical details described on the test request were recorded. Patients were followed up for up-to 36 months in linked hospital records for evidence of benign and serious (colorectal cancer, high-risk adenomas and bowel inflammation) colorectal disease. The diagnostic accuracy of FIT is reported by gender, age, and FIT threshold. Results In 9,896 adult patients with at least 6 months of follow-up, a FIT result ≥10 μg/g had an overall sensitivity for colorectal cancer of 90.5% (95% CI 84.9%-96.1%), women 90.0 (80.7-99.3), men 90.8 (83.7-97.8); overall specificity 91.3 (90.8-91.9), women 92.4 (91.8-93.1), men 89.8 (88.8-90.7); overall Positive Predictive Value (PPV) 10.1 (8.15-12.0), women 7.64 (5.24-10.0), men 12.5 (9.52-15.5)); and an overall Negative Predictive Value (NPV) 99.9 (99.8-100.0), women 99.8 (99.7-100.), men 99.9 (99.9-100.0). The PPV and specificity of FIT were higher for serious colorectal disease combined and the sensitivity and NPV were lower than for colorectal cancer alone. The Area Under the Curve (AUC) for all patients did not change substantially by increasing the minimum age of testing. In this population, 10% would be further investigated to detect 91% of the cancers at 10ug/g and 3% further investigated to detect 54% of the cancers at 150ug/g. The number needed to scope to detect one cancer was ten using FIT at 10ug/g. Conclusion A FIT threshold of 10 µg/g is appropriate to triage adult patients presenting to primary care with symptoms of serious colorectal disease. FIT may provide an appropriate approach to reprioritising patients colorectal cancer symptoms whose tests have been delayed by the COVID-19 pandemic. What is already known on this subject? Faecal Immunochemical Testing (FIT) is recommended by NICE to triage symptomatic primary care patients into further investigation for serious colorectal disease, including colorectal cancer. Almost no real-world data exists documenting the diagnostic accuracy of low FIT thresholds associated with colorectal cancer or serious colorectal disease in primary care with symptoms of colorectal cancer. What are the new findings? In 9,896 consecutive FITs submitted by English General Practitioners to a large English laboratory, using a threshold of 10ug/g, FIT had a sensitivity and specificity of 91% for colorectal cancer, a sensitivity of 53% and a specificity of 92% for serious colorectal disease. Of the population tested with FIT, 10% would be further investigated to detect 91% of the cancers at 10ug/g, 4% would be further investigated to detect 74% of the cancers at 50ug/g, and 3% further investigated to detect 54% of the cancers at 150ug/g. How might it impact on clinical practice in the foreseeable future? Low threshold FIT could be used as a triage test without overburdening endoscopy resources, supporting widespread implementation of the NICE recommendations for its use in low-risk patients in primary care. FIT may be an effective test for re-prioritizing patients whose endoscopy test have been deferred due to the COVID-19 pandemic to match available endoscopy resources to those at highest risk of colorectal cancer.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of Cushing's syndrome.

Clinical evaluation should guide those needing immediate investigation. Strict adherence to COVID-19 protection measures is necessary. Alternative ways of consultations (telephone, video) should be used. Early discussion with regional/national experts about investigation and management of potential and existing patients is strongly encouraged. Patients with moderate or severe clinical features need urgent investigation and management. Patients with active Cushing's syndrome, especially when severe, are immunocompromised and vigorous adherence to the principles of social isolation is recommended. In patients with mild features or in whom a diagnosis is less likely, clinical re-evaluation should be repeated at 3 and 6 months or deferred until the prevalence of SARS-CoV-2 has significantly decreased; however, those individuals should be encouraged to maintain social distancing. Diagnostic pathways may need to be very different from usual recommendations in order to reduce possible exposure to SARS-CoV-2. When extensive differential diagnostic testing and/or surgery is not feasible, it should be deferred and medical treatment should be initiated. Transsphenoidal pituitary surgery should be delayed during high SARS-CoV-2 viral prevalence. Medical management rather than surgery will be the used for most patients, since the short- to mid-term prognosis depends in most cases on hypercortisolism rather than its cause; it should be initiated promptly to minimize the risk of infection in these immunosuppressed patients. The risk/benefit ratio of these recommendations will need re-evaluation every 2-3 months from April 2020 in each country (and possibly local areas) and will depend on the local health care structure and phase of pandemic.

Endocrinology in the time of COVID-19: Management of pituitary tumours.

Patients with pituitary tumours, ensuing hormonal abnormalities and mass effects are usually followed in multidisciplinary pituitary clinics and can represent a management challenge even during the times of non-pandemic. The COVID-19 pandemic has put on hold routine medical care for hundreds of millions of patients around the globe, while many pituitary patients' evaluations cannot be delayed for too long. Furthermore, the majority of patients with pituitary tumours have co-morbidities potentially impacting the course and management of COVID-19 (e.g. hypopituitarism, diabetes mellitus, hypertension, obesity and cardiovascular disease). Here, we summarize some of the diagnostic and management dilemmas encountered, and provide guidance on safe and as effective as possible delivery of care in the COVID-19 era. We also attempt to address how pituitary services should be remodelled in the event of similar crises, while maintaining or even improving patient outcomes. Regular review of these recommendations and further adjustments are needed, depending on the evolution of the COVID-19 pandemic status. We consider that the utilization of successful models of pituitary multidisciplinary care implemented during the COVID-19 pandemic should continue after the crisis is over by using the valuable and exceptional experience gained during these challenging times.

Profiling ACE2 expression in colon tissue of healthy adults and colorectal cancer patients by single-cell transcriptome analysis (preprint)

A newly identified novel coronavirus (2019-nCoV) has caused numerous acute respiratory syndrome cases in Wuhan China from December 2019 to Feb 2020. Its fast spreading to other provinces in China and overseas is very likely causing a pandemic. Since the novel coronavirus has been reported to be capable of endangering thousands of lives, it is extremely important to find out how the coronavirus is transmitted in human organs. Apart from fever and respiratory complications, gastrointestinal symptoms are observed in some patients with 2019-nCoV but the significance remains undetermined. The cell receptor angiotensin covering enzyme II (ACE2), which is the major receptor of SARS-nCoV, has been reported to be a cellular entry receptor of 2019-nCoV as well. Here, to more precisely explore the potential pathogen transmission route of the 2019-nCoV infections in the gastrointestinal tract, we analyzed the ACE2 RNA expression profile in the colon tissue of healthy adults and colorectal cancer patients of our cohort and other databases. The data indicates that ACE2 is mainly expressed in epithelial cells of the colon. The expression of ACE2 is gradually increased from healthy control, adenoma to colorectal cancer patients in our cohort as well as in the external Asian datasets. According to the expression profile of ACE2 in colon epithelial cells, we speculate adenoma and colorectal cancer patients are more likely to be infected with 2019-nCoV than healthy people. Our data may provide a theoretical basis for the classification and management of future 2019-nCoV susceptibility people in clinical application.