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Draft a comprehensive differential diagnosis for acute substernal chest pain in a 45-year-old male with hypertension and hyperlipidemia, diaphoresis, exertional onset, and normal initial ECG/troponin; include life-threatening causes first, key distinguishing features, and immediate diagnostic next steps.

Draft a detailed differential diagnosis for new-onset unilateral throbbing headache with visual aura and brief monocular vision loss in a 32-year-old female on oral contraceptives; include red-flag symptoms, stroke/TIA considerations, and recommended initial workup.

Draft an assessment and plan for stage-2 hypertension (BP 162/98) in an obese 52-year-old with suspected obstructive sleep apnea; include ASCVD risk estimate, lifestyle prescriptions, first-line pharmacotherapy with drug/dose/targets, baseline labs/monitoring, and 4–6 week follow-up.

Draft an assessment and plan for type 2 diabetes follow-up with A1c 9.2% on metformin 1,000 mg BID and eGFR 65; compare adding a GLP-1 receptor agonist vs an SGLT2 inhibitor, address weight loss goals, hypoglycemia education, vaccinations, and micro/macrovascular screening.

Draft a history and physical for a patient presenting with chest pain, including HPI using OLDCARTS, pertinent ROS, PMH/meds/allergies, FH/SH, focused cardiac/pulmonary exam, initial labs and imaging orders, prioritized differential, HEART score risk stratification, and early management.

Draft a history and physical for a new patient with progressive exertional dyspnea, orthopnea, and bilateral leg edema; include differential (heart failure, COPD, PE, anemia, renal disease), targeted exam maneuvers, and first-line diagnostics and management.

Draft a progress note for COPD follow-up two weeks after an acute exacerbation treated with prednisone and antibiotics; include symptom trajectory, CAT score (if available), inhaler technique/adherence, oxygen needs, spirometry plan, smoking cessation counseling, and return precautions.

Draft a progress note for post-operative day 2 after total knee arthroplasty; include pain control strategy, DVT prophylaxis, PT/OT milestones, wound status, bowel/urinary function, labs/vitals review, complications screening, and discharge readiness.

Draft a discharge summary for community-acquired pneumonia admission; include admission/discharge dates, presenting symptoms, radiology/labs, pathogen if identified, inpatient therapies and response, discharge medications with durations, pending tests, follow-up appointments, and return precautions.

Draft a discharge summary for myocardial infarction managed with PCI and drug-eluting stent placement; include cath findings, complications, inpatient course, discharge medications (DAPT, statin, beta-blocker, ACEi/ARB), cardiac rehab referral, and follow-up plan.

Draft discharge instructions for a patient hospitalized with acute decompensated heart failure; include daily weights, sodium and fluid restriction amounts, medication list with dosing, signs of worsening heart failure, follow-up appointments, and lab monitoring plan.

Draft discharge instructions for an asthma exacerbation; include controller and reliever regimen, steroid taper schedule, spacer technique, trigger avoidance, a written asthma action plan, return precautions, and follow-up timing.

Draft a patient handout on managing high blood pressure in plain language; explain what BP numbers mean, key lifestyle steps (DASH diet, sodium limits, alcohol moderation), home BP monitoring instructions, medication adherence tips, and when to call the doctor.

Draft a patient handout for type 2 diabetes education in plain language; cover A1c goals, the plate method, physical activity targets, self-monitoring of blood glucose, hypoglycemia signs and the 15-15 rule, foot care basics, and a vaccination checklist.

Draft a summary of the latest CDC and WHO guidelines for managing community-acquired pneumonia in adults, including empiric antibiotic choices, duration of therapy, and follow-up recommendations.

Draft a plain-language overview of the ADA and AACE guidelines for diabetes management, focusing on A1c goals, weight management, and the use of GLP-1 receptor agonists and SGLT2 inhibitors.

Draft a summary of the 2024 USPSTF breast cancer screening recommendations, including updated screening intervals, risk-based approaches, and the role of MRI for high-risk patients.

Draft a concise summary of NCCN guidelines for melanoma management, including staging, surgical margins, adjuvant therapy, and checkpoint inhibitor recommendations.

Draft treatment alternatives for community-acquired MRSA skin infections in patients allergic to sulfa drugs; include oral and IV options, dosing, and duration.

Draft treatment alternatives for patients with type 2 diabetes who are unable to tolerate GLP-1 receptor agonists due to nausea; include medication substitutions and lifestyle recommendations.

Draft a summary of options for treating refractory depression, comparing ketamine infusions, transcranial magnetic stimulation (TMS), and electroconvulsive therapy (ECT).

Draft treatment options for advanced prostate cancer, including hormonal therapy, radiopharmaceuticals, and novel androgen receptor pathway inhibitors.

Draft a summary of recent research on mRNA vaccine technology beyond COVID-19, including applications in oncology and autoimmune disease prevention.

Draft an easy-to-understand overview of long COVID research, summarizing major symptoms, hypothesized mechanisms, and emerging treatment approaches.

Draft a summary of current research on Alzheimer’s disease biomarkers, including amyloid and tau imaging, and discuss how they influence diagnosis and trial design.

Draft an explanation of the interaction between warfarin and antibiotics such as ciprofloxacin or TMP-SMX, including INR effects and management recommendations.

Draft a summary evaluating drug interactions for patients taking Paxlovid and common cardiovascular drugs; include mechanism and recommended dose adjustments.

Draft a summary of the common and serious side effects of semaglutide, including GI intolerance, gallbladder disease, and thyroid-related warnings.

Draft an overview of potential side effects associated with long-term corticosteroid use, including osteoporosis, glucose intolerance, and adrenal suppression.

Draft a summary of essential lab tests to order in suspected acute pancreatitis, including amylase, lipase, liver enzymes, and metabolic panels, with interpretation guidance.

Draft laboratory workup recommendations for suspected hypothyroidism, including TSH, free T4, thyroid antibodies, and when to consider secondary causes.

Draft an explanation of which labs should be monitored in patients receiving methotrexate therapy, including CBC, LFTs, renal function, and frequency of monitoring.

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Research Article: Interpreting p53 IHC–TP53 NGS discordance in endometrial cancer: a mechanism-based diagnostic framework and clinical implications

Date Published: 2026-07-22

Abstract:
To analyse discordances between p53 immunohistochemistry (IHC) and TP53 next-generation sequencing (NGS) in endometrial cancer, with a focus on underlying mechanisms and their clinical implications. Despite increasing recognition of IHC–NGS discordance, a structured approach to its interpretation in routine practice remains lacking. A retrospective analysis was performed in 614 patients with endometrial cancer treated at two oncological centres between 2022 and 2025. All patients underwent both p53 IHC and TP53 NGS. Molecular classification followed the ProMisE hierarchy (POLEmut, MMRd/MSI-H, p53abn, NSMP). The subgroup of 110 patients with p53 abnormalities identified by p53 IHC and/or TP53 NGS (defined as an abnormal p53 IHC pattern, a TP53 mutation detected by NGS, or both) was analysed to identify and mechanistically classify IHC–NGS discordant cases, as discordance carries the most direct therapeutic implications within this subtype. Associations between molecular subtype and disease stage were evaluated using logistic regression. Among 110 patients with p53 abnormalities identified by p53 IHC and/or TP53 NGS, 23 IHC–NGS discordances were identified (20.9%). The most frequent source of discordance was difficulty in interpreting IHC expression thresholds (14/23; 60.9%), particularly around the 1% and 80% cut-offs. Other mechanisms included intratumoral heterogeneity with subclonal p53 expression (n=6), low-VAF TP53 mutations (n=2), and TP53 -independent p53 stabilisation (n=1). Discordant cases were systematically organised into seven mechanistic groups forming a structured interpretative framework. In the full cohort, p53abn was the only subtype significantly associated with advanced-stage disease (OR 1.79; 95% CI 1.06–3.03; p=0.031). IHC–NGS discordance in p53 assessment represents a multimechanistic phenomenon observed in over 20% of p53-abnormal cases. The proposed mechanism-based interpretative framework may support consistent evaluation of borderline cases and improve diagnostic decision-making in clinical practice. In clinically significant scenarios, particularly near diagnostic thresholds, pathological re-evaluation and supplementary NGS testing should be considered prior to treatment planning.

Introduction:
The introduction of molecular classification of endometrial cancer and the updated FIGO 2023 staging system has fundamentally changed the approach to this disease, shifting the focus from anatomical assessment to tumour biology ( 1 , 2 , 34 ). The central element of this new paradigm is p53 protein status — a key regulator of genomic stability. Abnormal p53 status, reflected by the p53abn subtype, is associated with the worst prognosis amongst all four molecular subtypes and directly influences adjuvant treatment…

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