United States

A non-common cause of constipation in an 86-year-old female with abdominal pain.
EstrellaAcosta, Katty MD1, and RodriguezMichel, Francisco J.MD2 
1Rotatory Internship Program, 2,3 Internal Medicine Department. Hospital Buen Samaritano, Aguadilla, PR.

Introduction: A cholecystocolonic fistula is an abnormal connection between the gallbladder and the colon. This condition is rare but can lead to significant clinical issues in patients presenting with cholelithiasis.
Case Summary: We present an 86-year-old woman admitted to our institution with the diagnosis of intestinal obstruction. The computed-tomography examination of the abdomen was consistent with a gallstone at the sigmoid colon. Intraoperatively, the calculus necrotized the gallbladder wall and formed a cholecystocolonic fistula, presented with severe colonic inflammation requiring a segmental resection of the colon with end-to-end anastomosis and cholecystectomy with a traditional open approach. The abdomen was closed. Her post-operative course was complicated by anuria that did not respond to aggressive intravenous fluid, persistent respiratory failure and asystole that did not respond to ACLS protocol.
Discussion: Inflammatory process for a long period of time allows the entrance of gallstone into the bowel through a fistulous tract. This case illustrates that a high index of suspicious is necessary in patients with cholelithiasis history, constipation, and radiologic evidence of pneumobilia.
Conclusion: Timely diagnosis and appropriate surgical management are crucial for favorable outcomes.



AMA Research Challenge 2024 

A non-common cause of constipation in an 86-year-old woman with abdominal pain

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Background: Necrotizing fasciitis is a rare life threatening infection characterized by progressive tissue destruction that may involve subcutaneous fat, fascia, and/or muscle. Gram-positive cocci, specifically strains of Staphylococcus aureus and Streptococci, are responsible for the majority of these single-site source infections. Polymicrobial infections occur as well because of a combination of gram-negative and anaerobic involvement. This case report presents a rare case of necrotizing fasciitis being caused by coagulase negative staphylococcus epidermidis and corynebacterium. 

Case Presentation: 
A 49-year-old male with past medical history of non-insulin dependent diabetes mellitus type 2 presented to the emergency department (ED) with a 2 day history of a progressively worsening right lower leg lesion. As per the patient, the lesion was initially erythematous and localized, but progressively expanded and began to develop bullae which prompted him to visit the ED. On arrival, the patient was tachycardic, febrile, and tachypneic. Labs were remarkable for leukocytosis with a neutrophilic predominance and an elevated blood glucose of 221. Blood cultures were collected and showed no growth in 5 days. However, wound cultures collected on the same day grew moderate corynebacterium and staph epidermidis within 24 hours. X-ray of tibia/fibula/ankle showed mild to moderate soft tissue edema about the medial malleolus and a small ankle joint effusion. Plastic surgery was consulted for bullae drainage and noted a large bullae on the medial aspect of the right tibia and erythema of the surrounding area. Wound debridement was recommended and performed on hospital day 4, 6, and 10. Intraoperative findings were consistent with necrotizing fasciitis, therefore muscular fascia was removed and split thickness autograft to the right leg was applied on hospital day 10, when intraoperative findings supported that the infection had resolved. Patient was treated with IV meropenem and doxycycline for 6 weeks and responded well to the autograft. 

Discussion:
Necrotizing fasciitis (NF) is typically caused by either a polymicrobial infection or Group A Streptococcus bacteria. Although diabetic patients tend to be susceptible to polymicrobial infections, it is very uncommon for the pathogens involved to only be those found on normal skin flora. Our case report shows that if there is a high index of suspicion, NF should still be considered even if wound cultures only grow bacteria typically present on normal skin flora. The aggressive progression of the infection despite the less common causative agents highlights the need for prompt recognition and intervention.


Aggressive Staphylococcus Epidermidis Infection Leading to Necrotizing Fasciitis: A Case Report 

Central nervous system lymphoma (CNSL) is a rare but aggressive subset of non-Hodgkin lymphoma (NHL). We present a case of a 48-year-old woman who presented with left-sided hemiparesis and facial droop. Patient has a past medical history of idiopathic thrombocytopenic purpura (ITP), retinal detachment, and subsequently tested positive for QuantiFERON-TB and IgG Toxocariasis. Initial imaging revealed multiple enhancing lesions, prompting concern for metastatic lesions or stroke. Extensive diagnostic workup including cerebrospinal fluid (CSF) analysis and biopsies led to the diagnosis of diffuse large B-cell lymphoma (DLBCL), the most common subtype. This case highlights the challenges in diagnosing CNSL, particularly in patients with concurrent medical conditions.

Approach to an Unclear Cause of Acute Weakness: A CNS Lymphoma Case Report 

Background
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, is a rare, X-linked recessive, genetic immune dysregulatory disorder affecting approximately 1 in 1-1.6 million individuals. The syndrome is classically characterized by the triad of severe enteritis and food allergy, infantile endocrinopathy (infantile diabetes or thyroiditis) and eczema. Symptoms
usually start in the first month of life. The prognosis is poor, with most children dying
in early childhood. In most cases, IPEX syndrome is caused by mutations in the FOXP3 gene, which leads to impairment of regulatory T cells. As a result, this immune dysregulation manifests as severe multi-organ autoimmunities.

Case Presentation
A 12-month-old male with eczema presented with a one-month history of non-bloody diarrhea. Parents reported 7-8 episodes of diarrhea per day without fevers or emesis. The patient was admitted for severe dehydration and malnutrition. His albumin and potassium levels were low (1.7g/dL and 2.8mmol/L respectively). Fecal occult blood test was positive. Additional workup guided by the gastroenterology service revealed multiple allergies on food allergy panel. IgA, tissue transglutaminase, fecal calprotectin and GI pathogen panel were negative. The
differential diagnosis included food allergy, malabsorption, and autoimmune enteritis including IPEX. Our patient was started on an amino acid formula, but no improvement in symptoms occurred. Biopsy results from an esophagogastroduodenoscopy and colonoscopy showed complete villous atrophy in the duodenum and chronic lymphocytic inflammation and apoptosis in the colon. Autoimmune screening labs including celiac disease panel, thyroid panel, anti-islet,
anti-thyroglobulin, insulin antibodies, anti-TPO were all negative. Considering persistent symptoms, steroid therapy was initiated while awaiting genetic testing. A likely pathogenic variant FOXP3 mutation (chrX, 767t>C hemizygous mutation) was identified. Steroid therapy yielded limited improvement, and our patient was transferred to a specialized facility for further management and potential hematopoietic stem cell transplant.

Discussion
The case highlights diagnostic challenges in recognizing atypical IPEX syndrome
presentations. Our patient had a delayed onset and had 2 out of the 3 classic systems [enteropathy, dermatitis, endocrinopathy] involved with IPEX syndrome. The severity and persistence of symptoms led us to pursue genetic testing, which revealed a FOXP3 mutation. IPEX can manifest later in life; the eldest known onset was at 12 years old. Enteropathy typically precedes endocrinopathies in late-onset cases. Effective management of IPEX involves a combination of immune suppression and dietary adjustments, with Hematopoietic Cell Transplantation (HCT) offering the sole curative option. This case suggests that IPEX should always be considered in the differential diagnosis of intractable diarrhea, especially in a child with eczema and/or endocrinopathies.

Beyond the Norm: Unraveling the Complexity of an Atypical Presentation in Immune,
Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked (IPEX) Syndrome

Introduction: A Roux-en-Y gastric bypass (RYGB) is a common bariatric surgery for weight loss, reducing the stomach size by creating a small pouch and bypassing a portion of the small intestine. While effective, RYGB can lead to complications, including nutritional deficiencies, anastomotic strictures, and, rarely, gastric remnant issues1. This case details a patient with persistent abdominal distension and pain who was found to have a gastric outlet obstruction (GOO) related to her RYGB performed over 20 years ago. 

Case: A 48-year-old female with sarcoidosis, rheumatoid arthritis, and a remote RYGB was admitted with septic shock secondary to MSSA bacteremia, complicated by mitral valve endocarditis and epidural abscess. Following abscess washout, the source of the bacteremia was determined to be cat scratches, and she recovered uneventfully. She also reported weeks of progressive bloating, abdominal pain, and poor appetite. CT imaging showed a fluid-filled and distended stomach. An upper GI study showed no evidence of obstruction of the efferent limb, suggesting an issue with the remnant stomach. A percutaneous gastrostomy (G)-tube was placed in the remnant stomach for decompression. Gastrograffin injected into the G-tube showed delayed gastric emptying with no contrast passage into the small bowel after 20 minutes, suggesting gastroparesis/gastric atony. A subsequent gastrograffin challenge showed contrast confined to the remnant, suspicious for GOO. The case was discussed amongst bariatrics and advanced gastroenterology teams, and the patient underwent an endoscopy through the G-tube, revealing a cratered ulcer at the pylorus of the excluded stomach and severe intrinsic stenosis which could not be traversed. She started on a proton pump inhibitor with plans for stricture balloon dilation. The patient was lost to follow-up and did not undergo the procedure. 

Discussion: Acute gastric remnant dilation is a rare postoperative complication of Roux-en-Y gastric bypass (LRYGB) occurring in 0 – 0.8% of cases2. This finding is unusual because the remnant pouch, being bypassed, is generally not expected to be actively involved in the digestive process. Dilation can be due to ulcer formation in the remnant stomach, as in this case, and has also been associated with diabetes and gastroparesis. Delayed diagnosis may lead to gastric remnant perforation, organ failure, sepsis, and death. This case underscores the role of internal medicine in managing complex inpatient presentations, especially those with incidental findings. The use of diverse imaging and procedural modalities like CT, upper GI studies, endoscopy was essential in diagnosing this atypical complication following RYGB.

Gastric Outlet Obstruction from Remnant Ulceration and Stricture: A Rare Complication Post RYGB

Background: The pectoralis major (PM) and pectoralis minor (PMi) are muscles located in the anterior chest wall. The pectoralis major is a fan-shaped muscle composed of the clavicular and sternocostal heads. Typically, the clavicular head originates from the anterior surface of the medial half of the clavicle. The sternocostal head, located just inferior to the clavicular head, originates from the anterior surface of the sternum, superior six costal cartilages, and aponeurosis of the external oblique muscle. The pectoralis minor lies deep to the pectoralis major, positioned on top of the rib cage. Innervation of these muscles is provided by the medial and lateral pectoral nerves.
Case Presentation: During a routine educational cadaveric dissection at the University of Toledo College of Medicine, asymmetrical pectoralis major muscles were identified in an 83-year-old male. Further examination revealed that the sternocostal head of the left pectoralis major was not fully developed. Additionally, the left pectoralis minor muscle was missing, and the left medial pectoral nerve was absent.
Discussion: Anomalous development of the pectoralis major is often associated with other musculoskeletal developmental defects, and the clinical presentation can vary depending on the involvement of structures. The PMi acts as a surgical landmark and can also be used as a myo-cutaneous flap in reconstructive surgeries. Understanding this anomaly can provide insights for managing cases of anomalous PM and PMi and have effects for future patients with pectoralis variations.


Hypogenic Pectoralis Major Muscle Associated with Complete Agenesis of Pectoralis Minor Muscle: Cadaveric Case Report

Background
Treprostinil is a synthetic prostacyclin analog, commonly used in the treatment of pulmonary hypertension. It can be given intravenously, subcutaneously via continuous pump, orally, or by inhalation. Typical adverse effects of the oral version include headache, nausea, vomiting, diarrhea, flushing, and dizziness. Here, we present a case report of an 80-year-old male with pulmonary hypertension (PH) who developed diffuse erythematous maculopapular rash while transitioning from intravenous treprostinil via subcutaneous pump to oral treprostinil.

Case Presentation
Patient is an 80-year-old male with severe pulmonary hypertension WHO group 1 and 3 who presented in clinic for evaluation of rash. He had previously been taking IV treprostinil 3.1 ng/kg/min via continuous subcutaneous pump for about eight months. He desired transition to oral treprostinil and began taking oral treprostinil 0.125 mg TID with plans to titrate up to 1 mg TID. On week two of the titration, while on 0.25 mg TID, the patient developed diffuse maculopapular erythematous rash, which was non-pruritic. He had no fever, mucosal involvement, or respiratory complications. Laboratory investigations revealed peripheral eosinophilia (0.84 K/uL, normal range <0.70 K/uL) but were otherwise normal. Serum IgE levels were within normal limits. Punch biopsy revealed orthokeratosis, mild spongiosis, and mild superficial perivascular and interstitial inflammatory infiltrate. These results indicated a dermal hypersensitivity reaction. Based on clinical picture, laboratory results, and histopathological findings, it was suspected that the patient’s rash was an idiosyncratic drug reaction associated with his upward titration of oral treprostinil. Patient was started on oral diphenhydramine 25 mg BID x10 days and oral prednisone 20 mg BID x7 days. The rash resolved within two weeks, therefore treprostinil titration was continued. The patient is now stable on oral treprostinil 1 mg TID without recurrence of rash. 

Discussion
Cutaneous adverse drug reactions (cADRs) pose a significant issue in the world of modern medicine, especially as medication regimens become more complex. Despite their frequency, information on incidence, symptomology, and long-term sequelae of cADRs is often underreported. Clinical trials of oral treprostinil have reported skin rash with little frequency. Furthermore, there do not appear to be any other case reports involving a maculopapular rash in response to oral treprostinil. Providers should be made aware of this rare reaction, espeically given the random, unpredictable nature of idiosyncratic drug reactions. Proper documentation of these cases is also crucial, as pharmacovigilance serves to advance scientific knowledge and improve patient care as a whole.

Maculopapular Rash Associated with Oral Treprostinil

Background: Cytokine Release Syndrome (CRS) is an acute inflammatory response syndrome marked by fever and/or multiorgan dysfunction and increased inflammatory cytokine release. CRS is generally observed in patients receiving CAR-T cell therapy, bispecific T cell engager therapy, or haploidentical hematopoietic cell transplantation. We present an intriguing case of Grade-3 CRS in a patient who recently contracted COVID-19 and was taking pembrolizumab.

Case Presentation: A 67-year-old man presented to the hospital with complaints of nausea, vomiting, diarrhea, and fever for two weeks. His family reported intermittent confusion, anorexia, and weight loss before hospital admission. Medical history was significant for metastatic renal cell carcinoma on pembrolizumab with axitinib for one year, CKD stage 3A, hypertension, left-sided nephrectomy, and recent COVID-19 infection four weeks ago. Physical examination revealed fever, tachycardia, tachypnea, and delirium. He was initially treated for severe sepsis with broad-spectrum antibiotic therapy but subsequently transferred to ICU for hypotension, and worsening delirium. Workup showed negative blood culture, urine culture, fungal culture, CSF culture, MRI brain, autoimmune connective tissue cascade, and paraneoplastic panel, albeit CRP was elevated to 239.3 mg/L. Due to worsening delirium, hypotension, and recent immunotherapy, there was clinical suspicion of CRS. Interleukin-6 level testing was ordered, and an elevated level of 1088 pg/mL was confirmed. He was given IV methyl prednisone 1 mg/kg on Day 7 of hospital admission, which improved his hypotension and minimal improvement in delirium. On Day 11, a one-time dose of tocilizumab was administered, and rapid resolution of delirium along with significant clinical improvement. After discharge, the oncology team discontinued pembrolizumab and started second-line therapy with cabozantinib.

Discussion: CRS is a frequently observed phenomenon in patients receiving CAR T-cell therapy and bispecific antibody therapies, often presenting with high fever, multiorgan failure, and elevated serum IL6 levels. Pembrolizumab is an immune checkpoint inhibitor (CPI), and several cases of CRS are reported in patients receiving this treatment. COVID-19 vaccination in patients receiving CPI therapy has been attributed to causing CRS-like symptoms in several reports. We observed a unique phenomenon in our patient who was receiving pembrolizumab for one year without side effects and presented with acute CRS after COVID-19 infection. Our literature review identified one other case of a patient presenting with acute COVID-19 infection, CRS symptoms, and colitis while receiving nivolumab/ipilimumab therapy. However, our patient had a delayed onset of CRS. Incidence of CRS is rare but has high mortality and requires prompt identification and treatment.

Post COVID Cytokine Release Syndrome in a Renal Cell Cancer Patient on Pembrolizumab Therapy

Background: Patients with bicuspid aortic valve (BAV) experience valvular complications at an accelerated rate. While BAV is generally regarded as a benign anatomical variant, recent histological and cardiac imaging studies suggest significant hemodynamic instability in even asymptomatic BAV patients.

Case Presentation: A previously healthy 59-year-old man was referred for new-onset difficult-to-control hypertension. Echocardiography revealed a mildly calcified but well-functioning bicuspid aortic valve (BAV) and there were signs of chronically elevated left-sided heart pressures, though the patient denied any symptoms and exercise stress testing was normal. Over the next 2 years he failed multiple antihypertensive drug regimens despite proper compliance. He eventually presented to the hospital with profound hypotension and was found to have infective endocarditis complicated by a perivalvular abscess requiring mechanical aortic valve replacement (AVR). Prior to AVR, he struggled to maintain blood pressure on a 3-drug regimen and his response to atenolol reflected that of elderly patients with isolated systolic hypertension from age-related aortic stiffening. Following AVR, a dramatic improvement was observed in the patient’s blood pressure, now responsive to nebivolol monotherapy at half the previous dose, and he has remained stable at 1, 3, and 6-month follow up.

Discussion: Hemodynamic instability and ascending aorta (AAo) stiffness are intimately associated with BAV, regardless of age, valvular function, aortic diameter, or atherosclerotic plaque burden. While the exact etiology of AAo stiffening in BAV patients has not been confirmed, recent histological studies suggest a similar–but
accelerated–mechanical stress-induced phenotypic shift in vascular smooth muscle cells (VSMCs) which has previously been implicated in thoracic aortic disease and age-related aortic stiffening. Reactive deposition of extracellular matrix initially serves to dampen mechanical stress and maintain homeostasis; however this ultimately increases pulse wave velocity (PWV) and central systolic pressure, perpetuating a feedforward loop of maladaptive stiffening and increased myocardial demand. Supporting these findings are recent strain imaging studies revealing subclinical diastolic dysfunction associated with aortic stiffness in asymptomatic BAV patients. Consensus guidelines for BAV surveillance currently address aortic aneurysm detection but fail to address its likely precursor–loss of AAo distensibility due to the intrinsic hemodynamic abnormalities of BAVs. Strain imaging offers immense value for this application but is not yet widely available in clinical practice. In the meantime, assessment of PWV on doppler echocardiography may be a valuable surrogate for aortic stiffness in
BAV patients.

Resolution of Hypertension Following Replacement of a “Well-Functioning” Bicuspid Aortic Valve

Background
Adverse childhood experiences (ACEs) are traumatic events like abuse or neglect that are associated with dangerous behaviors like violence and substance abuse during adulthood. ACEs contribute to the development of chronic non-communicable diseases like cardiovascular diseases, diabetes, and mental health disorders, which collectively account for over 70% of global deaths yearly. Research on ACEs has been limited in low-to-middle-income countries, like Honduras, which is ranked 5th globally in violence and 131st out of 191 in healthcare. The lack of studies on the driving factors behind violence and health disparities in Honduras has hindered the understanding of the relationship between ACES, violence, and health outcomes. Thus, this cross-sectional study aims to assess the impact of ACEs on violence and poor health outcomes amongst Honduran university students. 

Methods
This cross-sectional study comprised randomly selected students from Universidad Nacional Autónoma de Honduras which participated in a baseline eligibility screening survey followed by three self-administered Spanish questionnaires completed from 11/01/2023 to 11/05/2023. Questionnaires included ACEs, Maudsley Violence Questionnaire (MVQ), and Tobacco, Alcohol, Prescription Medications, and Other Substances (TAPS) questionnaires. The sample size of 287 Honduran University students comprised 101 males (SD=2.6) and 186 females (SD=2.6) with ages between 17-33 (M=21; SD=2.7). The relationship between ACEs and MVQ was assessed through correlation analyses (Pearson r). The relationship between ACEs or MVQ and TAPS was assessed using Spearman correlations (rho). The statistical significance was set at p<0.05.

Results
Participants completed the ACEs questionnaire, reporting experiencing 0 ACEs (14.2%), 1 ACE (12.8%), 2 ACEs (13.2%), 3 ACEs (20.2%), 4 ACEs (16.3%), 5 ACEs (9.75%), and 6+ ACEs (13.2%).

A positive correlation was observed between the number of ACEs and MVQ macho (Pearson’s r=0.16, P=0.0083). Tobacco usage showed a positive correlation with MVQ macho (rho=0.19) and total scores (rho=0.19, p-value=0.0015).
Drug usage was positively correlated with ACEs total (rho=0.12, p-value=0.0491), MVQ macho (rho=0.09, p-value=0.1327), MVQ acceptance (rho=0.12, p-value=0.0486), and MVQ total (rho=0.19, p-value=0.0014).

Medication usage showed positive correlations with total ACEs (rho=0.22, p-value=0.0001), MVQ macho (rho=0.17, p-value=0.0041), MVQ acceptance (rho=0.22, p-value=0.0002), and MVQ total (rho=0.19, p-value=0.0011).

Conclusion
This study identified a significant positive correlation between ACEs scores, MVQ scores, and TAPS scores. Over 80% of participants reported experiencing one ACE, aligning with research suggesting higher ACE scores in marginalized populations. The novelty of this research in Honduras offers insights that can inform national programs aimed at violence reduction and public health initiatives focused on preventing childhood trauma.

A Cross-Sectional Assessment of the Effects of Adverse Childhood Experiences (ACEs) on the Prevalence of Violence and Substance Abuse in Honduran University Students

Background
Female to male (FTM) and non-binary individuals assigned female at birth (transmasculine and non-binary people, or TMNB) who retain their assigned female at birth (AFAB) reproductive anatomy are recommended to have regular preventive screenings to evaluate for the risk of cervical cancer. However, evidence currently suggests that many TMNB persons have had negative experiences with pelvic exams that make them wary of visiting their current physician or of trying to find another provider. There is a need to evaluate the present barriers to care and how they can be addressed to make preventive gynecological care more accessible for this community.
Methods
We conducted a qualitative review of current literature on the TMNB OB-GYN experience and guidelines for conducting preventive reproductive care for the TMNB population.
Results
We identified several barriers to Pap smear access for the TMNB population, such as: anti-transgender discrimination within the healthcare workplace; gender dysphoria associated with the Pap smear procedure; feminine-coded environmental visuals and language in office spaces and educational materials; and insurance barriers. Some solutions were found, including developing coping strategies, administration of self-performed exams, improved healthcare professional education on the needs of the transgender population, and gender-inclusive language and visuals.
Conclusion
We recommend that the solutions recommended in the literature be implemented in both active clinics and in medical schools to enhance the accessibility of and minimize or eliminate negative experiences associated with preventive reproductive care for the transgender community.

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