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The endocrine paraneoplastic manifestations of cancer are well described and result from ectopic hormone production by non-endocrine organs or direct hormone secretion from endocrine malignancies. However, an emergent and more common issue is that of endocrine dysfunction associated with systemic anti-cancer therapies. These often present with vague symptoms but can be life-threatening and therefore awareness of these is essential. Here, we review the three most common paraneoplastic manifestations of cancer (hypercalceamia, syndrome of inappropriate antidiuretic hormone, Cushing's syndrome) and provide an overview of the endocrine complications of systemic anti-cancer therapies.

Bladder pain syndrome (BPS) is a condition of chronic bladder pain or discomfort that can significantly disrupt normal daily activities and reduce quality of life. It can be difficult to diagnose and manage because of vague symptoms, a poorly understood aetiology and few universally effective treatments. This article reviews the current literature on BPS aetiology, clinical presentation, diagnosis, and treatment options.

Background: Appendicitis is a common condition affecting 7-8% of the general population. With the improvement of noninvasive imaging, the diagnostic approach and treatment algorithm for patients with clear signs and symptoms suggestive of acute appendicitis are well agreed-upon. However, patients without pathognomonic signs and symptoms, but with equivocal imaging pose a diagnostic dilemma. These patients may still have acute appendicitis and could potentially benefit from laparoscopic appendectomy. This may be especially true in the subset of patients with appendicoliths. Methods: Our case series exams a group of patients with atypical symptoms who eventually underwent appendectomy and were followed after surgery for at least a month. This case series consists of eight patients with abdominal pain accompanied by a variety of other signs and symptoms in addition to laboratory results and imagining characteristics which were nondiagnostic. These patients had initial Alvarado scores ranging from 0-6. Results: All of these patients were subsequently taken to the operating room for diagnostic laparoscopy and laparoscopic appendectomy. Of these patients, six were known to have appendicoliths based on computed tomography obtained during initial diagnostic workup. Conclusions: All patients underwent a diagnostic laparoscopy and appendectomy. Four had appendicitis and four also had resolution of their symptoms. There exist atypical presentations of appendiceal disease. Patients with abdominal pain/tenderness, even without diagnostic laboratory results or imaging characteristics, may benefit from laparoscopic appendectomy.

Cerebrospinal fluid (CSF) peritoneal pseudocysts are a rare complication of ventriculoperitoneal shunts. They can manifest with symptoms of shunt malfunction or, more commonly, vague symptoms of abdominal discomfort such as pain or distention. The imaging features of peritoneal CSF pseudocysts may be nonspecific. In this case, we report a peritoneal CSF pseudocyst, which was initially mistaken for a complex hepatic cyst on both ultrasonography and MRI. The correct diagnosis was confirmed with a shuntogram and CT of the abdomen.

OBJECTIVEThe surgical indications for some arachnoid cysts (ACs) are controversial. While surgical procedures can be effective when an AC is a definite cause of hydrocephalus or papilledema, most ACs do not cause any symptoms or signs. Some surgeons perform several procedures to treat ACs because of their large size. The purpose of this study was to compare the long-term outcomes of Galassi type III ACs between surgery and nonsurgery groups.METHODSThe medical records of 60 patients diagnosed with sylvian ACs (Galassi type III) who visited Seoul National University Children’s Hospital from July 1990 to March 2018 were analyzed. The authors compared the outcomes between those treated with surgery and those not treated with surgery.RESULTSOf the 60 patients, 27 patients had no symptoms, 19 patients had vague symptoms and signs associated with ACs, and the remaining 14 patients had definite AC-related symptoms and signs. Thirty-eight patients underwent surgery, and 22 patients underwent observation. Some operations were accompanied by complications. Among the 33 patients in the surgery group, excluding 5 with hydrocephalus or papilledema, 8 patients needed 18 additional operations. However, there were no patients in the nonsurgery group who needed surgical intervention during the follow-up period (mean 67.5 months), although the size of the AC increased in 2 patients. Changes in AC size were not correlated with symptom relief.CONCLUSIONSWhen patients with hydrocephalus or papilledema were excluded, there was no difference in the outcomes between the surgery and nonsurgery groups regardless of the size of the sylvian AC. Surgeons should be cautious when deciding whether to operate.

BackgroundA pilot rapid diagnosis centre (RDC) allows GPs within targeted clusters to refer adults with vague and/or non-specific symptoms suspicious of cancer, who do not meet criteria for referral under an urgent suspected cancer (USC) pathway, to a multidisciplinary RDC clinic where they are seen within 1 week.AimTo explore the cost-effectiveness of the RDC compared with standard clinical practice.Design and settingCost-effectiveness modelling using routine data from Neath Port Talbot Hospital, Wales.MethodDiscrete-event simulation modelled a cohort of 1000 patients from referral to radiological diagnosis based on routine RDC and hospital data. Control patients were those referred to a USC pathway but then downgraded. Published sources provided estimates of patient quality of life (QoL) and pre-diagnosis anxiety. The model calculates time to diagnosis, costs, and quality-adjusted life years (QALYs), and estimates the probability of the RDC being a cost-effective strategy.ResultsThe RDC reduces mean time to diagnosis from 84.2 days in usual care to 5.9 days if a diagnosis is made at clinic, or 40.8 days if further investigations are booked during RDC. RDC provision is the superior strategy (that is, less costly and more effective) compared with standard clinical practice when run near or at full capacity. However, it is not cost-effective if capacity utilisation drops below 80%.ConclusionAn RDC for patients presenting with vague or non-specific symptoms suspicious of cancer in primary care reduces time to diagnosis and provides excellent value for money if run at ≥80% capacity.

CASE A 10-year-old boy presented with vague symptoms, a few days after a nondescript injury to his left knee. History, examination and blood tests, and imaging were unremarkable. Because of his severe pain, we proceeded to arthroscopy. On proceeding to arthroscopy, a wooden toothpick was found inside the knee joint. The wooden toothpick was removed arthroscopically. CONCLUSION The physicians/surgeons have to be vigilant and should approach holistically toward history and examination of a child presenting with vague signs and symptoms.

Bariatric surgeries have been increasing with the rising numbers of obese patients. Roux-en-Y is one of the safest and effective bariatric procedures worldwide. Internal hernia is one of laparoscopic Roux-en-Y gastric bypass complications. Its vague symptoms and late presentation may lead to adverse outcomes. Swirl sign in computed tomography scan has proven to be a particular and sensitive finding to detecting internal hernia in patients with an ambiguous presentation.

While the prevalence of syphilis had seen a significant decrease in the post-antibiotic era, it can still present in immunocompromised patients. While it is rare for immunocompetent patients to present with advanced stages of Syphilis, prompt recognition and diagnosis is imperative to prevent serious complications. We present the case of a 52 year old immunocompetent female who was diagnosed with syphilis 30 years ago who presented with vague symptoms including a rash, blurred vision, and headache and was diagnosed with early neurosyphilis.

We question the reliability of the vague symptoms that most commonly define catheter-associated urinary tract infection (CAUTI) and encourage further examination of whether the current CAUTI definition reflects a true infection. While diagnosing CAUTI using the current surveillance definition, physicians may be missing a number of nonurinary etiologies for fever, prematurely diagnosing urinary tract infection, and prescribing unnecessary antibiotics. We believe it is time to reconsider the quality metric of CAUTI. By doing so, we can improve antibiotic use and quality of patient care.

Graphical abstract, Highlights • Sinus of Valsalva aneurysm rupture is usually accompanied by heart failure symptoms. • Infected ruptured Sinus of Valsalva aneurysm is rare. • In patients without heart failure symptoms, prompt identification is crucial.

Differential diagnoses of vague neurologic symptoms in patients without significant medical history provide challenges for the advanced practice registered nurse to accurately diagnose a condition. A detailed inquiry highlights the nurse practitioner’s ability to hear the patient’s story, formulate an evidence-based diagnosis, and collaborate with the patient for delivering safe and effective care with appropriate referrals for specialist follow-up care. This case study emphasizes the importance of clustering symptoms that align, allowing for a better understanding of vague complaints, which helps the provider in clinical decision making.

Aortic dissection (AD) is a rare, time-sensitive, and potentially fatal condition that can present with subtle signs requiring timely diagnosis and intervention. Although definitive diagnosis is most accurately made through computed tomography angiography, this can be a time-consuming study and the patient may be unstable, thus preventing the study’s completion. Chest radiography (CXR) signs of AD are classically taught yet have poor diagnostic reliability. Point-of-care ultrasound (POCUS) is increasingly used by emergency physicians for the rapid diagnosis of emergent conditions, with multiple case reports illustrating the sonographic signs of AD. We present a case of Stanford type B AD diagnosed by POCUS in the emergency department in a patient with vague symptoms, normal CXR, and without aorta dilation. A subsequent review of CXR versus sonographic signs of AD is described.

Pancreatic cancer (PC) is one of the most lethal forms of cancers, ranking as the third highest cause of malignancies and fatalities. Approximately 88% of patients diagnosed with PC are older than 55 yr. Due to PC's vague symptoms, patients typically visit their doctor only when they experience symptoms of extreme pain and/or after their bile ducts have blocked. This produces symptoms including darkly colored urine, jaundice, and light-colored stools. At this point in the progression of the disease, the tumor has already metastasized. Early detection of PC is critical and justifies the need for innovative techniques to efficiently aid in this process. Current research involves screening different aspects of the disease, imaging techniques, and evaluating blood, urine, cell, and saliva biomarkers. We propose that forensic DNA fingerprinting can be used to establish the role of genetics in PC, and we describe disease inheritance patterns so that relatives can understand the likelihood of developing this lethal malignancy.

Among congenital renal anomalies, the ectopic kidney is a rare occurrence. Crossed fused renal ectopia (CFRE) - an even rarer subtype of ectopic kidney - is characterized by both kidneys being fused together on one side of the spine. CFRE is usually asymptomatic but can present with vague symptoms if the anomalous kidney becomes infected, is obstructed by calculus, or has a neoplastic change. There is no indication for surgical intervention if the kidney functions normally. This report presents a case of CFRE in a 31-year-old male with recurrent right flank pain resulting from a large calculus in the upper moiety of the fused kidney. The calculus was surgically removed by percutaneous nephrolithotomy (PCNL). The patient was discharged on analgesics, antibiotics, and potassium citrate tablets, with an order to follow up after one month. On follow-up, the patient's double-J (DJ) stent was removed and an X-ray was performed to rule out any complications. No signs of stones, strictures, or other complications were noticed.

Neurocysticercosis (NCC) is the most common parasitic infection of brain. Spinal NCC is commonly seen in association with cranial lesions. However, they do present rarely as isolated spinal lesions. Spinal NCC may present with vague symptoms, pain, paraparesis or, sometimes as, cauda equina syndrome. Spinal NCC with neurological deficits is an emergency, and it should be operated immediately followed by antiparasitic medications. We report a primary lumbar NCC patient, who presented with radicular pain. She underwent complete excision of cyst.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare variant of hepatocellular carcinoma, occurs in young adults. It presents with vague symptoms and diagnosed by imaging and biopsy. The treatment is surgery. We report a case of 15 years old male patient who was diagnosed with (FL-HCC) and treated with surgical resection.

Background Meckel’s diverticulum is the most frequent congenital anomaly of the gastrointestinal tract. It can invert or invaginate into the small intestine lumen. It is usually associated with heterotopic tissue elements. Case presentation We present a case of inverted Meckel's diverticulum, clinically and radiologically diagnosed as intestinal obstruction due to intussusceptions. The diagnosis was suspected due to target sign shown on radiological examination. Pathologically, it was inverted Meckel's diverticulum obstructing the lumen in parallel plan mimicking the telescoping appearance, with heterotopic pancreatic tissue formed of exocrine and ductal components only. Conclusions Inverted Meckel’s diverticulum may present by vague symptoms and may simulate other causes of intestinal obstruction.

On March 5, 1984, Bennington College freshman Libby Zion died at New York Hospital. She had been admitted the night before with vague symptoms and strange jerking motions. After consulting with her family physician, the residents on call gave her intravenous solutions for possible dehydration and prescribed meperidine to control her jerking motions. They then left to take care of other patients. Luise Weinstein, the first-year resident, was responsible for 40 other patients. No sleep for her.

Pathology of sphenoid sinus is uncommon and may pose a diagnostic challenge in view of its vague symptoms together with its relatively inaccessible location at the skull base. Radiological imaging is of utmost importance in diagnosis. We present an insidious case of a sphenoid sinus cholesterol granuloma.

Restless leg syndrome (RLS) or Willis-Ekbom disease (WED) is an under-diagnosed, chronic, and progressive primary sensory-motor disorder. It is characterized by an uncontrollable urge to move the legs due to uncomfortable and sometimes painful sensations, with a diurnal variation. RLS can lead to severe sleep disturbances, a usual cause of consultation. The pathophysiology is known partially, and it is believed that there is an association between the different variants of genetic mutations combined with dopaminergic and brain iron dysregulation, which plays an important role. The data used for this study were extracted from the articles found in the PubMed database that discuss different gene variants, pathophysiology, and various methods of treatment. They also highlight the role of iron in the pathogenesis of RLS as it is required for the synthesis of tyrosine hydroxylase, which is the rate-limiting step for dopamine synthesis. This review article provides a clinically useful overview of RLS in terms of pathophysiological findings, its genetic associations, and therapeutic options by using the currently available literature. Because RLS presents with vague symptoms and shares similarities with many other diseases, it might be overlooked by many physicians resulting in underdiagnosis and under-treatment. While these discoveries provide a breakthrough in understanding the details of RLS, further studies are recommended as these studies are limited to animal models and provide a limited representation of the general population.

This article focuses on the symptomatic and diagnostic problems of primary duodenal adenocarcinoma by way of two case reports and a literature review.The diagnosis of primary duodenal adenocarcinoma is often delayed because its symptoms may be absent until the tumor has progressed, thus leading to a delay of several months. Patients typically present with a long history of variable and vague symptoms, and many are diagnosed with advanced disease. As regards clinical manifestations, abdominal pain is the most frequent symptom. The majority of these tumors are found to have infiltrated the duodenal wall at presentation, with many being unresectable due to local and distal invasion.

Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

Bone tumours in childhood cause considerable anxiety to both parents and children. They may present with vague symptoms or a fracture and are often confused with osteomyelitis. Benign lesions account for the majority of bone lesions. Primary malignant tumours of bone make up for 6% of all childhood malignancies. Diagnosis may be guided by clinical assessment and imaging. However, a firm diagnosis depends upon the histopathology and immunohistochemistry. Thus, a multidisciplinary team approach is vital to the diagnosis and management of bone tumours.

Although rare, pancreatic cancer usually has a poor prognosis. Margaret Ann Perry explains the risk factors for, and diagnosis and treatment of, the disease Despite improved survival for those with many types of cancer, pancreatic cancer has continued to have poor outcomes. This article was written following the loss of a popular and well respected colleague who recently passed away from this devastating disease. It aims to alert practice nurses to the vague symptoms of pancreatic cancer, its diagnosis and management, and improve knowledge and understanding of this much-feared cancer type.

Background: Abnormalities of mesonephric ducts are rare congenital conditions, which can present with vague symptoms in otherwise healthy men. Zinner's syndrome is the association of an enlarged seminal vesicle cyst with ipsilateral renal agenesis, which can be symptomatic and require operative interventions. Case: We present the case of an otherwise healthy 24-year-old man who presented with a symptomatic 15 cm seminal vesicle cyst, which was completely excised using a robot-assisted approach. Conclusion: Use of robotic surgery for excision of large seminal vesicle cysts is a safe and effective operative procedure.

326 Background: At the Rapid Access Diagnostic Unit at Guy’s Hospital London, we review patients with vague symptoms that are concerning for malignancy. As part of our response to the COVID-19 pandemic, we developed a virtual triage pathway with the aim to reduce face-to-face appointments and prioritise resources towards patients with an underlying cancer diagnosis. Methods: Patients were triaged by clinicians based on a telephone consultation with the patient and history and blood tests provided in the referral. Those triaged as high risk were either directly booked for investigation (“straight-to-test”) or booked for a face-to-face consultation for further history and examination. Low risk patients were either put on a watch-and-wait pathway with a telephone follow-up in 3-4 weeks or discharged back to the GP with a robust plan on symptom management. The patient outcomes were tracked and compared to the outcomes from the face-to-face assessment service used prior to the COVID-19 pandemic (Dec 2016-Feb 2020). Patients triaged as low risk and discharged were tracked to monitor for any subsequent cancer diagnoses. Results: There were 804 referrals triaged between March 2020-January 2021. 75% were triaged to a face-to-face assessment and 18% triaged straight-to-test. 4% were placed on the watch-and-wait pathway and 3% were returned to the GP with advice. In those triaged as high risk, 8.2% were diagnosed with cancer, 54% were diagnosed with a serious-benign condition and 38% with a non-serious or no condition. In the patients triaged as low risk and placed on the watch-and-wait pathway, 14% were brought in for a face-to-face assessment based on their follow-up telephone assessment. None of the patients on the watch-and-wait pathway were found to have a cancer diagnosis, 11% were diagnosed with a serious-benign condition, and 89% were diagnosed with a non-serious or no condition. There was an overall cancer diagnosis rate of 7.6% compared with a pre-COVID-19 diagnosis rate of 6.6%. Conclusions: The virtual triage pathway effectively risk-assessed patients, with those triaged as high risk having an 8.2% cancer diagnosis rate compared to a 0% cancer diagnosis rate in those triaged as low risk. Furthermore, the virtual triage service had a higher cancer diagnosis rate compared to the pre-COVID-19 face-to-face assessment service. Therefore the virtual triage service provides an efficient pathway for cancer diagnosis in patients presenting with vague symptoms, reducing the number of face-to-face appointments and supporting management of low risk patients in the community.

Coarctation of the aorta is a rare finding in adults and can present with vague symptoms. We report a case of a 64-year-old cognitively impaired female who presented with fatigue and tinnitus. After extensive workup, she was diagnosed with coarctation of the aorta and subsequently underwent repair. After operative intervention for her coarctation, her cognitive impairment was found to have an objective improvement evidenced by the Montreal Cognitive Assessment.

Background: Most studies show that women with symptoms of acute coronary syndrome (ACS) delay seeking care longer than men do. Contributing factors include women being more likely to experience diverse symptoms, to experience symptoms that do not match preexisting symptom expectations, to interpret symptoms as noncardiac, and to minimize symptoms until they become incapacitating.Objective: The aim of the study is to identify factors influencing women’s ability to recognize and accurately interpret symptoms of suspected ACS.Methods: This qualitative study used in-depth interviews with 18 women diagnosed with ACS to determine how they recognized, interpreted, and acted on symptoms. An interview guide developed from the author’s initial research was used to provide structure for the process.Results: All of the women went through a process of recognizing and interpreting their symptoms. Eight women had symptoms arise abruptly. Most of these women recognized a change immediately, “knew” to go for treatment, and did so quickly. Three women had vague symptoms that started slowly, converting unexpectedly to intense symptoms prompting them to seek care urgently. The remaining 7 women had evolving symptoms, were more likely to interpret symptoms as unrelated to their heart, and avoided disclosing symptoms to others. Despite recognizing that the situation may be serious, women with evolving symptoms adopted a wait-and-see approach.Conclusion: Women with less severe, intermittent, or evolving symptoms are at increased risk for delayed presentation, diagnosis, and treatment for ACS. These women should be targeted for educational and behavioral interventions.

Bladder pain syndrome (BPS), previously recognized as interstitial cystitis and painful bladder syndrome, is a chronic pelvic pain condition that can be significantly debilitating and decrease quality of life for women. The etiology of BPS is unknown, and it is diagnosed by exclusion. BPS remains difficult to diagnose and manage because of vague symptoms and a lack of universally effective treatments. This article reviews the current literature about BPS etiology, clinical presentation, diagnosis, and treatment options.

Detection of a posterior glenoid labral lesion can be challenging. Clinicians may overlook this diagnosis because of its vague symptoms, unlike rotator cuff tear or adhesive capsulitis. Together with magnetic resonance (MR) imaging, shoulder MR arthrography is considered the imaging method of choice for the detection of posterior glenoid labral lesions. However, MR arthrography is associated with high cost and low accessibility, and to circumvent these shortcomings, efforts are being made to use sonography (US). However, prior experience in shoulder US is required to evaluate glenoid labrum using US because glenoid labrum is not located superficially and is surrounded by the rotator cuff musculature. There were a few studies that reported the potential for arthrosonography in finding the tear of anterior glenoid labrum and rotator cuff. Until now, however, there was no report regarding arthrosonography in posterosuperior glenoid labral tear and its efficacy and potential for overcoming the limitations of conventional US. In this report, we described 3 cases with posterosuperior glenoid labral tear that were not diagnosed by conventional US but by arthrosonography. In addition, the authors also present their history, physical examinations, and response to treatment, which may be helpful in the diagnosis of posterosuperior glenoid labral tear.

Tickborne diseases are increasing in the United States, and the geographic range of tick vectors is expanding. Tickborne diseases are challenging to diagnose, as they present with vague symptoms such as fever, constitutional symptoms, and nonspecific laboratory abnormalities. A high degree of clinical suspicion is required to make a diagnosis, as patients often do not recall a tick bite. The availability of laboratory testing for tickborne diseases is limited, especially in the acute setting. Therefore, if a tickborne disease is suspected, empiric therapy should often be initiated before laboratory confirmation of the disease is available. This article summarizes the most common non-Lyme tickborne diseases in the United States.

This report describes a case of neurosyphilis presenting with memory disturbances, attention deficit, and acute psychotic decompensation in an immunocompetent man. Despite the known connection of neurosyphilis with psychiatric symptoms, this cause often remains unrecognized. This report emphasizes the importance of maintaining a suspicion for the disease in patients with vague symptoms and describes the diagnostic difficulties. Keywords: Neurosyphilis, CSF pleocytosis, Immunocompetence, Dural thickening

Neuroendocrine tumors (NET), such as insulinomas and carcinoid tumors, can be challenging to diagnose since patients often present with vague symptoms. Adding to the challenge, these tumors are often occult on typical cross-sectional imaging modalities. Because of these challenges, there has been an increase in the utilization of radiopharmaceuticals that take advantage of specific receptors expressed by NET. Among the multiple radiopharmaceuticals that can be used, (68)Ga DOTATATE is emerging as the most sensitive and specific imaging agent. We present a case where (68)Ga DOTATATE was used to diagnose a well-differentiated neuroendocrine tumor.

We present the case of a 75-year-old man with vague symptoms and hypotension found to be in electrical storm secondary to sustained ventricular tachycardia. The patient did not respond to intravenous amiodarone, magnesium, lidocaine, or four cardioversion attempts. This case illustrates the challenges in managing patients with electrical storm presenting to the emergency department.

Abdominal tuberculosis is a common form of extrapulmonary tuberculosis. Often it is difficult to diagnose due to vague symptoms and lack of clinical findings. Spigelian hernia is a rare type of hernia located in the semilunar fascia of the abdominal rectus muscular sheath. We report on a 19-year-old Greenlandic Inuit man with a spigelian hernia as the primary presentation of abdominal tuberculosis. Abdominal tuberculosis presenting with a spigelian hernia is extremely rare, and the case illustrates that tuberculosis may present in myriad ways. The incidence of tuberculosis in Greenland is among one of the highest in the world, and we also review the history and incidence of tuberculosis in this Arctic country.

This chapter examines “the unsaid” that readers and healthcare providers regularly encounter. It provides training in attention to the implicit meanings. It does so by presenting a vignette of a physician’s follow-up interview of patient presenting vague symptoms, in which he discovers what his patient leaves out of the interview. It also presents a similar short story by James Joyce, “Araby,” where it is left to the reader to discover what is unsaid by the protagonist. Finally, it presents Dr. William Carlos Williams’s poem “The Red Wheelbarrow,” which enjoins its readers to discover what is important about the poem. This chapter is related to Appendix 6, which examines strategies of teaching Ernest Hemingway’s story, “Indian Camp,” to medical students.

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.

Pulmonary involvement in Henoch‐Schonlein purpura (HSP) although rare is an important treatable cause of hospital admission in patients. Its diagnosis is difficult due to the vague symptoms and non-specific radiographic findings. We present one such case of a known case of HSP presenting with pulmonary involvement and treated successfully with steroids and immunosuppressant medications after ruling out all other causes. This particular case could also have an additional component of methotrexate induced lung involvement. Overall it is an interesting case with some much needed learning points.

Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern recently described in the literature with fewer than 120 cases published. AFOP is often difficult to diagnose and may be mistaken for other pulmonary disorders such as interstitial pneumonias or pneumonitides. Patients often present with vague symptoms of cough, dyspnea, hemoptysis, fatigue, and occasionally respiratory failure. Radiological findings show diffuse patchy opacities and ground glass appearance of the lungs. On histologic examination, intra-alveolar fibrin balls are observed. We discuss a case of a man who presented with hemoptysis and dyspnea and whose open lung biopsy revealed AFOP. We will describe the presentation, diagnosis, and post-discharge course, and review the current literature. There are only 4 cases which have reported the patients' course of disease after 1 year, the longest being 2 years. To our knowledge, this is the only case of AFOP in the literature that describes the course of a patient more than 2 years after the diagnosis of AFOP, and is the most comprehensive review of the current literature.

Isolated gallbladder injury, secondary to a blunt abdominal trauma, is a rare finding in children.The presence of vague symptoms and the unknown dynamic of the trauma may increase the diagnostic challenge especially in pediatrics.A conservative management has been proposed in some particular cases in adults, but remains controversial in children.We report a case of a 5 year old boy who presented an isolated gallbladder lesion secondary to a blunt abdominal trauma.The surgical treatment was delayed for non-medical reasons, which gave us the possibility to try a conservative approach. Keywords: Isolated, Gallbladder injury, Blunt trauma, Conservative approach

Fibrous dysplasia (FD) is a rare, benign osseous tumor, whereby normal bone architecture is replaced by haphazard fibrous tissue. Temporal bone involvement is extremely rare and presents with vague symptoms. We present a case of temporal bone FD in an adolescent girl who presented with progressive unilateral hearing loss, which was successfully managed surgically with canal wall down mastoidectomy with no recurrence. FD although rare, has a tendency for cataclysmic complications if not discerned early.

Synovial chondromatosis is a rare, benign cartilaginous metaplasia that affects the joints, is uncommon in the temporomandibular joint (TMJ), and is difficult to diagnose because of its generally vague symptoms. In the present report we emphasize the importance of the correct diagnosis in a noncommon location. A male patient reported recurrent episodes of dislocation and pain in the left TMJ. In the clinical examination an oral opening limitation was observed, and tomographic sections showed hyperdense, circumscribed, well-defined area in the joint space, measuring approximately 2 mm. It was surgically removed, and the histologic slices revealed a hypocellular hyaline cartilage fragment whose gaps were filled by nonatypical chondrocytes. Therefore, the histopathologic study is essential to differentiate it from a chondrosarcoma. The patient is under follow-up and is without recurrences.

Foramen of Winslow hernias are one of the most uncommon types of internal hernias that a surgeon will encounter. They are often initially indolent with vague symptoms that present over an extended period of time. Unfortunately, these hernias are not often diagnosed prior to requiring emergent operative intervention. This case report describes a patient who had a long history of vague abdominal pain and radiographic evidence of a foramen of Winslow hernia 4 years prior to presenting with acute obstructive symptoms. This raises the question: Should foramen of Winslow hernias, if diagnosed early, be repaired on an elective basis?

Background Pica is a relatively common phenomenon in pregnancy and typically includes consumption of nontoxic substances such as earth/clay, raw starches, and ice. Occasionally, substances may be toxic or have unintended consequences. Case A nulliparous woman presented to our facility complaining of numerous, vague symptoms that are common in pregnancy. She had multiple work-ups and an admission to our antepartum unit without clear etiology of her symptoms. Ultimately, she was diagnosed with talcum powder toxicosis secondary to talc ingestion as a coping mechanism for her anxiety, which was heightened in pregnancy. Conclusion This case highlights the importance of screening for mental health disorders, which may be exacerbated during the peripartum period. Patients' coping mechanisms for mental health disorders may have unintended consequences.

An inverted (intussuscepted) appendix is a rare finding, often mistaken for a polyp as it presents with vague symptoms. This can result in misdiagnosis and inappropriate management. Diagnosis is usually made through surgery. Rarely, endometriosis has been found as the cause of the intussusception. A 42-year-old woman presented with frequent loose stools over 2 years, an elevated calprotectin over 400 μg/g faeces (normal

Restless legs syndrome (RLS) is a chronic neurological disorder affecting a growing number of people. Patients describe an irresistible urge to move their lower limbs in times of immobility. Due to its vague symptoms and similarity to other disorders, it has become increasingly difficult for primary care clinicians to properly diagnose and manage RLS. As a result, patients with RLS are routinely misdiagnosed and continue their lives without proper management. This literature review examines the current understanding of the disorder, provides key points to assist clinicians in differentiating RLS from similar disorders, and explores recently updated evidence-based guidelines for the effective management of RLS.