The Socrates Project for Difficult Diagnosis at Northwestern Medicine

Northwestern’s Chief Medical Residents (CMRs) serve as the fellows for the service, and one of them assumes primary responsibility for each new consultation request the service receives. After obtaining the patient’s case history from the referring provider, the CMR then undertakes a thorough review of the electronic health record and any other available records from other institutions. In the inpatient setting, the CMR performs a new history and physical; phone calls or video conferencing permit history taking for outpatients. In contrast with the standard consultant note, we do not redocument the history, physical, and lab and imaging findings but instead construct a detailed problem list that synthesizes relevant findings into a useful working document.

The service’s faculty leader (BDS) then reviews the problem list with the CMRs to help refine the problem list and begin producing a differential diagnosis during a weekly hour-long meeting. As evidence supports team-based diagnostic collaborations,² the problem list and preliminary differential diagnosis then becomes a shareable document that the CMR or team leader presents to ad hoc general internists, specialists, and the other CMRs. The presentation can be in person, by phone, or e-mail. These ad hoc members, approximately 20 in number and spanning from junior attending physicians to senior clinicians, have volunteered to help the Socrates Project by adding their thoughts on differential diagnoses that explain the problem list and how to move forward with further testing. The ad hoc members have self-identified as clinicians with an interest in medical diagnosis—including surgeons, neurologists, psychiatrists, radiologists, and pathologists—and range in expertise from general internists to subspecialists. Finally, we document our problem list, differential diagnosis, and recommendations in the medical record and discuss the case with the referring team. The service limits its scope of clinical recommendation to diagnosis and avoids commenting on management decisions outside of the use of therapies as empiric diagnostic tests. A sample note is provided as an online Appendix.

Despite our process, we are often left without a satisfying diagnosis. We then are then faced with three possibilities: (1) The diagnosis is identifiable, just not by the physicians involved in the case—we did not think of the diagnosis in our deliberations; (2) The diagnosis is a described condition but without an available test—autoimmune limbic encephalitis associated with an unassayable or unknown auto-antibody, or the acuity of a critically ill patient makes diagnostic testing unreliable or not feasible; (3) The diagnosis has not yet been described by medical science—we are seeing a case of HIV infection in 1971.

With the personnel and process outlined above, we hope to provide recommendations that are useful in guiding a diagnostic workup regardless of which of these three scenarios is applicable. Our flexibility with involving the appropriate specialists in the Socrates Project should minimize the number of patients with a knowable diagnosis that is unknown to us. In the second scenario, our recommendations may rest upon the incorporation of a treatment as a diagnostic test. In the limbic encephalitis example above, a trial of steroids with rapid improvement in the patient’s condition may increase diagnostic certainty. The third scenario is the most difficult to identify. Pattern recognition of similarly presenting patients, keeping ourselves updated on pertinent primary literature, and consideration of advanced diagnostic testing such as exome sequencing and other next-generation sequencing strategies are essential in hoping to characterize a specific clinical syndrome that has yet to be described.

For situations in which our recommendations do not yield a diagnosis, we recognize the role for protocols such as genomic or metagenomic sequencing that assess multiple diagnostic possibilities in parallel without an a priori hypothesis.^3,4 The utility of multi-omics testing in diagnostic workups has been detailed by the Undiagnosed Diseases Network (UDN), which has created a systematic approach to describing new syndromes with the aid of metabolomic and genomic profiling.⁵ It is important to note that even with the resources available to the UDN, the diagnosis rate is 35%, emphasizing that in the majority of diagnosis-refractory cases, a diagnosis will not be found. This low diagnosis rate underscores the need for continued inquiry and cataloging of cases and data for further review or synthesis as the body of medical knowledge continues to expand. For these reasons, we have a follow-up system in place, which involves the assigned CMR regularly reviewing the chart and reporting during our weekly meetings. We make phone calls to patients and providers for cases that appear to be lost to follow-up.