United States


One of the most prevalent non-epithelial tumors of the GI mesenchyme are Gastrointestinal Stromal Tumors (GISTs). Less than 1% of all malignancies are stromal tumors, but knowledge of their etiology and signaling pathways can lead to the identification of new molecular targets for potential therapeutic development. One of the drugs which shows remarkable action against GIST is imatinib, a tyrosine kinase inhibitor.

Here we present a patient with a long term history of minimal pericardial effusion who was hospitalized after an echocardiogram revealed a recent development of significantly increased pericardial effusion associated with shortness of breath(SOB). She was diagnosed with GIST a year ago, following which she was started on imatinib. She presented to the ER with complaints of left sided chest pain. ECG revealed atrial fibrillation and echo showed a moderate sized pericardial effusion. After clinical examination, pericardiocentesis was done, which aspirated 500 ml of bloody pericardial fluid, and a drain was placed. Following which, the patient still continued to have SOB, and on further workup, a left sided pleural effusion was detected on chest x-ray. Fluids from both effusions were aspirated and sent to pathology to rule out malignancy. Patient had recurrent bilateral pleural effusion after discharge which was later drained on subsequent hospitalization. 

This case report highlights incidence pleural and pericardial effusion post treatment of GIST with Imatinib. Although imatinib is generally well tolerated, it does cause both atrial fibrillation and pleural/pericardial effusions in rare cases. In these cases, it becomes essential to perform a thorough workup so as to rule out other possibilities such as metastasis, malignancy or infection.


2022 AMA Research Challenge

New Onset Pleural-Pericardial Effusion and Paroxysmal Atrial Fibrillation in an 83-year-old Female with Gastro-Intestinal Stromal Tumor (GIST) After Starting Imatinib Treatment

Welcome to the inaugural International Sarcopenia Translational Research Conference.  “Where Worlds Meet” – the event brings together a broad range of researchers and practitioners in a truly interdisciplinary forum, covering discovery science through to clinical practice.

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ISTRC 2021 - International Sarcopenia Translational Research Conference

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Ricardo Correa, MD, EdD
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Jessica Li, MD/PhD Candidate
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Charles Lopresto, DO

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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Background
Mycophenolate acid (MPA) is an immunosuppressive drug commonly used in heart transplantation to prevent allograft rejection. There are two common preparations, mycophenolate mofetil (Cellcept) and mycophenolate sodium (Myfortic), which are absorbed differently. We present a case of a heart transplant recipient with a prior partial colectomy and gastroparesis who had recurrent biopsy negative rejection.
Case Presentation
A 21-year-old male with history of partial colectomy underwent uncomplicated orthotopic heart transplant. Eighteen months after transplant he displayed an unexpected elevation of donor derived cell free DNA accompanied by very low level de novo DSA’s (MFI<2500). He underwent endomyocardial biopsy that was negative for evidence of cellular or antibody mediated rejection. Coronaries were angiographically normal. He was electively treated for suspected subclinical AMR with plasmapheresis, rituxan, bortezomib, and solumedrol. Two months later he re-presented to our institution in cardiogenic shock requiring an intra-aortic balloon pump and inotropes. Repeat coronary angiography showed severe multivessel vasculopathy (CAV-3), including acute thrombotic occlusions of the OM branch and r-PDA. Although serum tacrolimus troughs had been maintained at goal post-transplant, a serum MPA level was undetectable at time of admission. He was changed from Cellcept to Myfortic, but remained with persistent severe allograft dysfunction despite a second salvage course of treatment for underlying AMR, and is now listed for re-transplantation.
Discussion
We suspect this is a case of early onset severe AMR and vasculopathy was related to inadequate immunosuppression due to mycophenolate mofetil malabsorption in this patient with a prior hemicolectomy and gastroparesis. Use of an alternative mycophenolate formulation with better absorption profile, and closer monitoring of serum MPA levels should be considered in heart transplant recipients who has similar history of gastrointestinal disease and surgery.

Severe Allograft Vasculopathy and Antibody Mediated Rejection in Heart Transplant Recipient

Atrial fibrillation (AF) can result in thromboembolism with devastating consequences. The CHA2DS2-VASc score is used to stratify thromboembolic risk in AF patients, but more patient-specific biomarkers for thrombosis such as D-dimer should also be included in risk assessment and indication for anticoagulation therapy.

Value of D-dimer in risk stratification for thromboembolism in patients with atrial fibrillation and low CHA2DS2-VASc score

Background
Anorectal malformations (ARM) are common anomalies encountered in pediatric surgery, between 1 in 2000 and 1 in 5000 live births result in an ARM diagnosis. Rarely is an ARM diagnosed after the neonatal period. Many different anorectal defects can occur in females including cloaca, anal atresia, and ectopic anus. Ectopic anus is considered a low anorectal anomaly and most frequently occurs in the perineum and vulva.
Case Presentation
Our patient is a 35 year-old female with a past medical history of hypothyroidism and congenital pes planus. She presented with a possible fistula from a sexual assault that occurred as a child. She denied any urinary tract infections, dysuria, or dyspareunia. She complained of some fecal incontinence and difficulty achieving intimacy due to feeling “abnormal.”
During colonoscopy it was discovered she had a posteriorly located ectopic anus in the vaginal introitus with a normal anorectal ring in the correct more posterior position. MRI confirmed the diagnosis of a fourchette ectopic anus with no other genitourinary abnormalities.
Our surgical approach focused on restoring normal anal and vaginal function and appearance. We achieved this through a perineal anoplasty, reconstruction and reinforcement of the posterior vaginal wall with an omental flap, and a Stage 2 neurostimulator. This resulted in a normal-appearing and functional anus and vagina.
Discussion
Here we present a unique case of a patient with an ARM diagnosed in adulthood. She presented with a history of sexual assault during childhood, fecal incontinence, and difficulty achieving normal sexual function. An MRI confirmed the diagnosis of a vaginal ectopic anus. The patient had no complaints of urinary tract infection or other genitourinary symptoms. ARMs are commonly detected in the neonatal period and are rarely seen during adulthood. Most cases discovered during adulthood happen in resource-limited environments. ARMs should be diagnosed within the first 24 hours of life during neonatal examination. However, in underdeveloped regions, more births may happen at home rather than hospitals thus contributing to inconsistency in healthcare in the immediate neonatal period and may play a role in missing ARM diagnoses.

Case Report: Ectopic Anus in the Vaginal Introitus in a 35 year-old Female

Adenocarcinoma of the anus is a rare form of cancer, accounting for only 10% of primary anal carcinoma diagnoses. This case involves a 65-year-old female with an incidentally discovered anal mass. 

The patient was initially admitted for COPD exacerbation and iron deficiency anemia. On physical exam, the patient was found to have an anal mass at the 8 o’clock position. Further history revealed that she had experienced bleeding and painful defecation for the last 3 months. Subsequently, the patient underwent a left inguinal and anal node biopsy to determine tumor origin and progression. The mass was biopsied, and immunohistochemistry was performed. Staining demonstrated strong reactivity for cytokeratin 7 and focal reactivity for p16. These markers indicated an adenocarcinoma of anal origin. Diverting colostomy was performed to allow for wound healing and prevent further blood loss. She continues to be followed by oncology for further evaluation and treatment.

Clinically, the significance of distinguishing the origin of anal canal tumors is the mechanism of spread, which reflects the dual lymphatic drainage system. A colorectal adenocarcinoma carries an increased risk of spread via the inguinal and femoral nodal chains compared with a rectum-based adenocarcinoma. Histochemical staining with glands positive for cytokeratin 7 can be used to classify tissue as ductal or glandular in origin. However, the histological pattern of anal gland adenocarcinoma remains to be sharply defined, thus strengthening the need for further exploration within the literature. Further classification and understanding among multiple disciplines of medicine are pertinent to better treatments and prognosis in patients presenting with anal adenocarcinoma. 

Adenocarcinoma of the anal canal accounts for 2.7% of all gastrointestinal malignancies. The limited number of studies and discussions in the literature make it challenging as a pathological diagnosis and for appropriate clinical management. As more cases are reviewed, there is an increased opportunity for treatment development and prognosis improvement.

Incidental Discovery of Advanced Primary Anal Adenocarcinoma

Background: Colorectal cancer is the second leading cause of cancer deaths in the United States. Synchronous cancers occur rarely, representing approximately 3.5% of all colorectal cancers. When compared to open colectomies, laparoscopy has been shown to have similar oncologic outcomes with shorter hospital stays and lower 30-day mortality. Additionally, intraoperative fluorescence angiography (IFA) provides an objective assessment of bowel and anastomotic perfusion.

Case Presentation: Here we present the case of a 74-year-old lady who had synchronous ascending and sigmoid colon adenocarcinomas, treated with a laparoscopic resection. She initially underwent a colonoscopy for evaluation of symptomatic anemia which revealed an ascending colon adenocarcinoma. The bowel prep was poor however, and repeat colonoscopy revealed a synchronous adenocarcinoma in the sigmoid colon. We performed a laparoscopic total abdominal colectomy with primary end-to-end ileorectal anastomosis and IFA with indocyanine green (ICG). The procedure was successfully completed laparoscopically. A total of 8 ports were used. The extraction site incision measured 6cm. IFA with ICG showed good perfusion of the small bowel conduit and ileorectal anastomosis. Final pathology revealed a right colonic well-differentiated pT2 adenocarcinoma (16.5cm proximal margin), a moderately differentiated pT2 distal sigmoid colon adenocarcinoma (7.5cm distal margin), and 48 benign lymph nodes. These findings represented an optimal oncologic resection with adequate lymph node harvest and margin status. The patient recovered well and was ready for discharge home on postoperative day 4 without need for narcotics. She continues to be well 4 months after surgery.

Discussion: Assessment for synchronous lesions is critical in the evaluation of colorectal cancer patients. This case highlights a rare case of synchronous colon cancers and exemplifies the advantages of laparoscopic technique. It also illustrates the utility of intraoperative bowel perfusion assessment with fluorescence angiography, which has been associated with lower anastomotic leak rates.


Minimally Invasive Treatment of Synchronous Colon Cancers

Background: 
Although Mycobacterium chelonae is ubiquitously found in the environment, cutaneous infections with M. chelonae are rarely reported. The few reported cases generally feature opportunistic infections in immunocompromised hosts. Due to its uncommon nature, providers often overlook this mycobacterium as the causative agent of a painful erythematous rash in their differential diagnosis. This case highlights common presentations and features of M. chelonae infection and demonstrates the importance of looking to ordinarily benign organisms as harmful and virulent in our immunocompromised population. 

Case Presentation: 
A 48-year-old female with refractory Behçet’s disease, maintained on methylprednisolone and apremilast, presented for a painful rash on her left lower extremity. She reported two months of tender nodules spreading from her ankle up to her medial thigh. Exam revealed erythematous and violaceous nodules in a sporotrichoid pattern. Three skin biopsies were performed over a period of two months; the first two were inconclusive, while the third showed marked dermal and subcutaneous inflammation with microabscess formation. Fite and AFB stains highlighted acid fast organisms. Subsequent acid-fast bacilli tissue culture grew M. chelonae.

The patient was initiated on triple antibiotic therapy with tobramycin, linezolid, and clarithromycin; however, her course was complicated by drug-induced liver injury. She was then transitioned to tobramycin and imipenem, leading to acute kidney injury and rhabdomyolysis. This prompted a final shift to imipenem and omadacycline, which was ultimately successful in resolving the rash.

Discussion: 
Although cutaneous infections with M. chelonae and other atypical mycobacteria are rare, providers should maintain a high level of suspicion in immunocompromised patients presenting with skin lesions, especially in a sporotrichoid pattern. Violaceous nodules in immunocompromised hosts should always warrant an infectious work-up. The diagnosis of atypical mycobacterial cutaneous infections in a timely fashion may be challenging. Multiple representative biopsies may be required for histopathological examination, which should include acid-fast staining, followed by routine bacterial and mycobacterial culture to achieve the most accurate diagnosis.


A Case of Atypical Mycobacterial Infection in a Patient with Bechet's Disease

Herpes genitalis caused by herpes simplex virus type 2 (HSV-2) is estimated to affect approximately 45 million adults in the United States. Over the past two decades, increasing HSV resistance to acyclovir has been noted among immunocompromised patients. HSV refractory to acyclovir is a complex clinical challenge with few alternatives available.

A 42-year-old woman with a past medical history of mycosis fungoides presented to the hospital with painful well-defined, edematous labial erosions that worsened from her previous admission. During this last admission, HSV-2 was detected on skin swabs via PCR from labia majora lesions. Punched-out discrete erythematous coalescing erosions were observed on the buttocks, groin, and proximal thighs, in addition to sloughing of the skin and grey-brown exudate. Initial therapy with intravenous (IV) acyclovir was transitioned to topical cidofovir cream and IV foscarnet due to suspected acyclovir resistance. Susceptibility testing confirmed acyclovir resistance and sensitivity to foscarnet. Despite improvement, foscarnet and cidofovir were discontinued due to dysuria and chemical burns, respectively. Our patient's decreased renal function made her a poor candidate for guideline-recommended IV cidofovir and high-dose acyclovir. Consequently, she was enrolled in a clinical trial for the novel antiviral priteliver. Hospitalization was further complicated by polymicrobial bacteremia, for which she was placed on continuous renal replacement therapy due to worsening acidosis and acute kidney injury. The priteliver was discontinued due to oliguria and worsening renal failure leaving the patient with no viable options. Given the severity of her lesions and concern for possible viral encephalitis, the infectious disease team determined that restarting treatment with IV foscarnet would outweigh the renal risks of therapy.

With the emergence of acyclovir-resistant HSV, clinicians must stay up to date with alternative treatments. The use of second-line agents, such as foscarnet and cidofovir, requires special consideration as these drugs are associated with higher toxicity. Unfortunately, foscarnet's nephrotoxicity complicated our patient's clinical course. Novel antivirals will provide better tools to tackle this clinical challenge. Priteliver is designed to inhibit viral replication by targeting the HSV helicase primase and is currently in an ongoing open-label trial to assess efficacy and safety in immunocompromised patients.

Acyclovir-resistant herpes simplex virus in a mycosis fungoides patient

While alopecia is common in patients with adrenoleukodystrophy (ALD), characterization of the hair loss pattern is poorly understood and is often reported as male androgenetic alopecia. In a previous case report, a scalp biopsy in an ALD patient diagnosed with androgenetic alopecia demonstrated sebaceous hypertrophy on H&E findings, with hair shaft structural abnormalities on scanning electron microscopy (EM), suggesting an an alternate alopecia mechanism. A 14 year old male with cerebral ALD presented to our institution with a clinical picture that matched a non-scarring alopecia, yet his scalp biopsy electron microscopy results were consistent with a non-inflammatory scarring alopecia. This case illustrates the variety of structural abnormalities underlying alopecia in ALD, and further research is needed to better understand the disease process.


Alopecia in a Pediatric Patient with Adrenoleukodystrophy

Background
Linear porokeratosis is a rare subtype of porokeratosis, a group of keratinization disorders. All porokeratosis disorders share the histopathological feature of a coronoid lamella, seen as columns of parakeratosis and dyskeratotic cells found in the granular layer of the epidermis. Linear porokeratosis presents in childhood with hyperkeratotic plaques, typically arranged in a unilateral linear formation that follow a Blaschko line distribution or dermatomes. Current therapies are reported to have unsatisfactory outcomes. Topical cholesterol 2%/ lovastatin 2% cream has been proven to be effective in some forms of porokeratosis, but has limited studies in the linear form. 

Case Presentation
A 61-year-old male presented to his family physician with erythematous plaques on the bilateral upper extremity of over 50 years duration. He has tried and failed standard treatment, including clobetasol, calcipotriene cream and diclofenac gel. Clinical presentation and pathologic examination of a skin biopsy revealing a coronoid lamellae were consistent with bilateral linear porokeratosis. Through a PubMed search, there have been limited reported cases of unilateral linear porokeratosis, but there have not been any reported cases of bilateral linear porokeratosis.

Discussion
A current theory for development is a two-hit mutation in the phosphomevalonate kinase (PVMK) and mevalonate diphosphate decarboxylase (MVD) genes of the cholesterol synthesis pathway, causing loss of function of the genes. These mutated genes inhibit the cholesterol synthesis pathway. Because cholesterol is an essential factor in the overall health of the stratum corneum, cholesterol depletion causes premature apoptosis of the keratinocytes, leading to the formation of the porokeratosis. 
The compounded cholesterol 2%/lovastatin 2% ointment provided a profound decrease in the hyperkeratotic scaling and erythema associated with our patient’s bilateral linear porokeratosis. After a 12 week trial, the overall size of the patches and plaques were significantly reduced in the treated areas. The mechanism of action of the targeted therapy and the results our patient achieved support the two-hit mutation theory (loss of function mutations in PVMK and MVD) in causing of linear porokeratosis. Cholesterol and lovastatin have an established safety profile and offers a relatively inexpensive alternative treatment option that may have better outcomes than current standard therapies. 


Bilateral Linear Porokeratosis Treated with Topical Cholesterol 2%/ Lovastatin 2%

“CHRONIC WOUND MANAGEMENT AND SOCIOECONOMIC BARRIERS IN A STREET MEDICINE SETTING”
Jesse Obregon, Taha F. Rasul, Brittany J. Blake, Orly Morgan, Julie Schnur, Armen Henderson
Miami Street Medicine Institute, University of Miami Miller School of Medicine


Background
Persons experiencing homelessness (PEH) have decreased access to longitudinal care which means that they often present to providers in advanced disease stages. Street Medicine providers in low resource settings should consider cost-effective methods of managing patients with chronic wounds in order to prevent the development of complications. We present two cases in which Street Medicine providers used physical exam findings and a multifaceted approach to manage chronic wounds of differing etiologies. 
Case Presentation
Patient 1: A 53-year-old male was seen with multiple, acute and chronic facial wounds. He had been hospitalized multiple times in the past year due to seizure activity. He had been prescribed Levetiracetam, however did not take the medication due to side effects and limited access to refills. 
The street medicine team provided wound care, counseled on medication adherence, and coordinated an appointment at a nearby low-income clinic. Two weeks later, he had refilled his medication and did not have any further facial or bodily trauma. 
Patient 2: A 65-year-old unsheltered male with a history of liver disease was encountered for left leg non-healing ulcer. He was hesitant to receive care at any clinical setting. Initially, the wound was approximately 12 x 9 cm in size with purulent drainage and foul odor. Wound care provided consisted of saline irrigation, gentle debridement, bandaging, and multivitamin tablets. He was also provided with wound care supplies for self-service. Over the next 6 months, his wound shrunk to 8 x 7.5 cm in size with the presence of granulation tissue without erythema or malodorous discharge.

Discussion
The first case demonstrates how monitoring facial wound healing processes served as a clinical marker of seizure disorder improvement. Connecting that patient to primary care by leveraging community resources and medication refills helped in the improvement of his seizure disorder. The second case provided a challenge as the patient was resistant to help for his wound care and medical condition. Consistent wound care likely decreased the risk of severe complications such as cellulitis, osteomyelitis, and abscesses. Street medicine organizations can serve as a bridge for PEH from the street to the clinical setting. 


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New Onset Pleural-Pericardial Effusion and Paroxysmal Atrial Fibrillation in an 83-year-old Female with Gastro-Intestinal Stromal Tumor (GIST) After Starting Imatinib Treatment

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