United States

Background: Metformin is a widely prescribed medication for the management of type 2 diabetes. It is known to have a high safety index, however it can cause serious adverse effects such as lactic acidosis, particularly in patients with chronic kidney disease. Elderly patients are at higher risk of developing Metformin-Associated Lactic Acidosis (MALA) due to aging kidney. We aim to highlight the importance of early adjustment of metformin and propose development of guidelines with higher estimated glomerular filtration rate (eGFR) for deprescribing metformin in older adults in contrast to younger population. 

Case Presentation: An 82 year old male with a past medical history of Diabetes, Chronic kidney disease 2, Atrial fibrillation on apixaban, Stroke and Chronic stage 4 sacral decubitus ulcer was sent to the emergency department (ED) for altered mental status. He was admitted to the intensive care unit for management of septic shock, PEA cardiac arrest and acute hypoxemic respiratory failure requiring intubation. Labs showed lactic acidosis and anion gap metabolic acidosis in the setting of no infectious source. Patient had chronic kidney disease with acute renal failure on metformin. He was diagnosed with Metformin Associated Lactic Acidosis. 

Discussion: This case highlights the potential risks associated with metformin use in older adults with CKD and AKI from infections, dehydration and decreasing oral intake due to acute illness, aging or dementia. There are expected physiological changes in the aging kidney including cellular dysfunction and nephrosclerosis that can cause unexpected kidney injury in older adults causing their eGFR to drop acutely. Age-related changes in renal function and decreased clearance of drugs place elderly patients at higher risk of developing MALA. New guidelines for higher eGFR for deprescribing metformin should be considered in older adults. This could prevent morbidity, mortality and adverse outcomes in the frail older diabetic population. 


2023 AMA Research Challenge

Metformin Associated Lactic Acidosis in an Elderly Patient: A Case Report

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Background
In the United States, approximately 294,000 suffer from spinal cord injury (SCI). There are an estimated 17,810 new cases each year. People with SCIs are susceptible to the same medical conditions as their non-injured counterparts. Some conditions may be more difficult to diagnose in SCI patients based on presenting symptoms.

Case Presentation
A 70-year-old female with past medical history of T4 paraplegia presented with subacute onset of pruritic rash and acute onset shoulder and orofacial weakness. The rash began on her shoulders before spreading diffusely; an initial outpatient trial of oral and topical steroids did not improve symptoms. Two weeks following the rash onset, the patient noted proximal shoulder weakness described as 30% of her baseline strength. Notably, the patient’s husband passed away two weeks prior to presentation. Review of systems was positive for diminished appetite, fatigue, chills, abdominal distension, constipation, weakness, and rash. On physical exam, the patient had numerous pink/violaceous papules and plaques noted on extremities, chest, back, and head. Skin biopsy showed dermatomyositis. Steroids were started and rheumatology workup was significant for positive antinuclear antibody and elevated creatinine kinase. CT abdomen/pelvis showed enhancing omental nodularity, concerning for carcinomatosis. Tumor markers were notable for elevated CA-125. Omental biopsy revealed metastatic adenocarcinoma of Mullerian origin. Upon discharge, the patient was diagnosed with paraneoplastic dermatomyositis secondary to ovarian cancer with oncology follow-up and steroid therapy for dermatomyositis.

Discussion
It is important to keep a broad differential diagnosis in patients presenting with a chief complaint of weakness, particularly in those with SCI in which new onset weakness may be difficult to assess clinically. Dermatomyositis and Polymyositis are important diagnoses to consider, particularly when the weakness is symmetric and proximal. Patients with SCI may not note these hallmark symptoms, so one must utilize the full physical exam. Classic dermatomyositis skin findings can clue the examiner into the potential diagnosis even in the absence of assessable weakness. In adult-onset disease, the risk is approximately 20%–32% for an associated internal malignancy, making it imperative to make a diagnosis to ensure a prompt oncologic workup is completed. Additionally, weakness is a commonly noted symptom of bereavement, which may lead providers to attribute similar symptoms to somatic complaints when social history aligns. Our case illustrates the importance of maintaining a broad differential in patients whom weakness is difficult to elicit and not anchoring on social history when evaluating a subjective chief complaint like weakness.


Weakness in a patient with spinal cord injury: A broad differential is key


Background
The recent regulation of xylazine, a veterinary sedative and analgesic, has exposed its escalating threat to public health. The growing misuse of xylazine due to its sedative effects and its concomitant use with opioids like fentanyl for cost-cutting further intensifies the opioid crisis. Xylazine use poses significant risks, including overdose, addiction, withdrawal, and severe tissue damage at the injection site. Xylazine acts on the central nervous system via alpha-2-receptor agonism. This case highlights the challenges of outpatient management of xylazine withdrawal and wound care, emphasizing the immediate need for effective interventions to address this public health issue.

Case Presentation
We report the case of a 41-year-old female on a methadone maintenance program who presented to the clinic with a large necrotic wound on her left forearm. The patient reported injecting xylazine into the wound multiple times daily. Initial assessment revealed a multistage wound with eschar covering a significant portion of the forearm. Despite the alarming features of the wound, the patient declined hospitalization and residential drug treatment. A decision was made to closely monitor her as an outpatient with treatment goals to discontinue xylazine use, prevent wound infection, and facilitate wound healing. The treatment plan included doxycycline for infection prophylaxis and wound care with collagenase, followed by Medihoney dressing. Withdrawal symptoms were managed using clonidine, gabapentin, and ondansetron, which were prescribed cautiously due to their abuse potential. With pharmacologic interventions and close outpatient follow-up, the patient stopped using xylazine and adhered to the treatment plan. The wound transitioned from necrotic to viable tissue, but an exposed extensor tendon necessitated a referral to a higher level of care, which the patient declined.

Discussion
Managing xylazine withdrawal and xylazine-associated wounds in an outpatient setting is challenging due to limited guidelines, medication misuse potential, and patients' hesitance toward hospitalization. Tailored treatment plans, close monitoring, and patient collaboration are vital. Wound care is crucial in preventing further deterioration and facilitating tissue regeneration. However, specialized management for the exposed extensor tendon was declined. Managing xylazine withdrawal with limited medication quantities and close monitoring presented additional challenges. The success of this outpatient management relied on collaboration and communication, fostering compliance and therapeutic alliance. This case highlights the challenges of managing xylazine misuse and emphasizes the need for individualized approaches and further research.

Managing Xylazine Misuse in Outpatient Settings: Challenges and Interventions

Metaplastic breast cancer (MBC) is a rare, aggressive subtype that often presents unilaterally as a high-grade large tumor with solid or cystic components compared to other forms of breast cancer. MBC was only recently recognized as a distinct pathologic diagnosis, so knowledge is limited in its pathogenesis, patient demographics, presentation, or standard treatment guidelines. Although knowledge is limited, MBC is most commonly diagnosed in women between the ages of 55 to 60 and is often chemotherapy resistant and reoccurs. MBC carries a poor prognosis with a survival rate of less than 1 year for patients with distant metastasis. We present a case of MBC diagnosed in a 28 year-old Afghani female that presented with increasingly worsening swelling and erythema of her left breast, without any other classical signs of breast cancer including skin dimpling, nipple changes or discharge, or fever. This patient demonstrates an unusual presentation of rare metaplastic breast cancer in a younger patient than normally diagnosed, further showing the unpredictable nature of this disease. Further research to improve diagnosis, treatment, and survival rates of patients with metaplastic breast cancer is needed with further exploration of targeted therapies and increased familiarity of the disease for the publication of standard treatment guidelines. 


Presentation of Rare Triple Negative Metaplastic Breast Cancer in a 28 year-old Female: A Case Report

INTRODUCTION
Mondor’s disease (MD) is a rare, self-limited, benign thrombophlebitis
(manifesting as a palpable cord-like induration) which typically resolves in 4-8
weeks without any specific treatment. We present a Mondor’s disease patient who has had the lesion for over a decade without a formal diagnosis.

CASE PRESENTATION
An 81-year-old female with a history of bilateral mastectomy (right breast in
(1996 and left breast in 2001) with subsequent right-sided mammoplasty and
left-sided implant, presented to the emergency department and admitted after a
mechanical fall.

She was incidentally found to have a beady, non-tender, cord-like structure in
the periumbilical region; the overlying skin appeared normal (Figure 1). The
patient stated this lesion had been present for over 10 years with prior
symptomatic management with oral analgesics. A doppler ultrasound (Figure 2)
revealed no blood flow and confirmed the diagnosis of Mondor's disease.
The patient opted for conservative management, therefore no further treatment
was administered.

DISCUSSION
Mondor's Disease is caused by a sclerosing thrombophlebitis of superficial
veins in the breast and commonly the anterior thoracoabdominal wall, which
usually resolves within 1-2 months. MD is a rare entity, with approximately 500
cases described in medical literature.

Possible risk factors include breast cancer, mammoplasty, trauma, muscular
strain, venous compression from clothing/bandages and intravenous drug use.
Essentially linked to Virchow’s Triad. The male to female ratio has been quoted
as 3:1; however, published cases are mostly females.

MD is characterized by the onset of a subcutaneous cord-like induration; the
overlying skin is usually normal and freely mobile. MD is a clinical diagnosis
confirmed by history and physical examination with confirmation by a doppler
ultrasound showing absent blood flow within the vein.

A standardized management for MD has not been established due to its rarity
and its tendency for spontaneous resolution within 1-2 months. In painful cases,
NSAIDs have been demonstrated to be effective in pain relief.
Administration of subcutaneous low molecular weight heparin (LMWH) has
been reported as effective in counteracting the blood hypercoagulability in the
acute phase in some cases of MD.

Our case is unique because Mondor’s disease is a self-limiting condition which
usually resolves in a few weeks however, our patient had MD for over a
decade. Currently there is no guideline for long term management for chronic
cases.

CONCLUSION 
Physicians should consider Mondor's disease for patients who present with cord like structure within the thoracoabdominal wall in the setting of a previous breast cancer, mammoplasty, or breast augmentation. The patient may be reassured that in the majority of the cases presentation is self limited.


It's still there? A patient presenting with Mondor's disease

Methanol is a highly toxic, colorless, volatile alcohol that is present in homemade beverages, paint removers, windshield liquid, anti-freeze, shellac, and perfumes. Although uncommon in the United States, methanol poisoning can occur with improper distillation of spirits. Over 50% of morbidity and mortality associated with methanol poisoning is accidental in nature and therefore preventable. Methanol poisoning, even in small quantities of 50 to 100 ml, is associated with severe complications such as permanent blindness.


Methanol Poisoning Presenting With Bilateral Basal Ganglia Hemmorhage

Introduction


Clozapine is an atypical antipsychotic, which has offered a ray of hope to many patients afflicted by treatment resistant schizophrenia including treating its positive symptoms and bipolar disorder. Nevertheless, the drug`s side effect profile limits its use. This case report emphasizes that the side effects are not solely confined to clozapine but can be dosage related and can be potentiated by anticholinergics.
Recent studies show that the case fatality rate is as high as 27.5 % in patients affected by gastrointestinal hypomotility rather than agranulocytosis.


Case presentation
A 34‐year‐old man was brought to the emergency department in refractory circulatory shock following a 2‐day history of profound diarrhea, abdominal distension, and vomiting. GCS score was below 8, Patient was intubated and transferred to ICU.
His medical history is significant for Resistant Bipolar disorder type 1 and chronic constipation. He was on quetiapine, benztropine and clozapine. Clozapine was gradually increased from 100 to 450 mg a day over three months that worsened his constipation despite being on senna.


He was resuscitated with crystalloids and started on vasopressors. Labs showed Acute kidney injury, rhabdomyolysis, and elevated liver enzymes. CT of the abdomen pelvis without contrast revealed fecal impaction with diffuse enterocolitis with distal colonic obstruction. The patient was treated initially with crystalloids, bowel rest, nasogastric decompression, and broad-spectrum antibiotics. Patient required enema and manual disimpaction. Enteral feeds were started. Patient`s ICU stay was prolonged secondary to relapse of his symptoms including agitation and anxiety requiring dexmedetomidine. He was transferred to floors on lorazepam and quetiapine on day 10 and discharged on day 30 with 100 mg of clozapine and benztropine.




Discussion
Randomized controlled trials (RCTs) have demonstrated significant decline in hospital admissions and length of stay following the initiation of clozapine in individuals with bipolar disorder and schizophrenia, along with an increase in quality-adjusted life years (QALYs). However, the relative prevalence of intestinal side effects associated with clozapine, ranging from constipation and ileus to bowel perforation are reported to be as high as 33%. Consequently, it is crucial to implement measures that allow for its continued use to benefit patients, rather than replacing it with alternative treatments. 
Conclusion
We offer the following suggestions to patients on clozapine:
Increased surveillance for bowel dysfunction and proactive management of early bowel dysmotility by ensuring daily bowel opening.
Add an extra dose of osmotic laxative with colonic stimulant monthly if needed.
Xray abdomen every 3 months.


Clozapine and benztropine associated functional bowel obstruction, an un-noticed dreadful adverse effect: A case report


A rare case of Vancomycin and Piperacillin-Tazobactam induced transaminitis

Is empiric therapy best for everyone? A rare case of Vancomycin and Piperacillin-Tazobactam induced transaminitis in the setting of fatty liver disease 


Background: 
Tricuspid endocarditis (TE) associated with intravenous drug use (IVDU) presents unique management challenges, including recurrent infections and poor treatment adherence. The pathophysiology involves direct inoculation of pathogens through contaminated injection equipment, leading to valve colonization and infection. While most cases of tricuspid valve infective endocarditis can be managed with antibiotics alone, surgical intervention is considered in specific circumstances. The choice between prolonged oral (PO) antibiotics and intravenous (IV) antibiotics in patients with active IVDU requires careful evaluation of risks and benefits. 

Case Presentation: 
We present the case of a 49-year-old female with active IVDU and TE, complicated by infective endocarditis and treatment noncompliance. Initially, the patient was not recommended a prolonged course of IV antibiotics due to concerns about the risk of relapse. However, the patient's father, recognizing her high-risk profile for suicide and death, emphasized the need for IV antibiotics, further complicating the decision-making process. Five months later, the patient's noncompliance with PO antibiotics resulted in a severe decompensation, leading to admission into the intensive care unit. The patient ultimately underwent tricuspid valve replacement and pacemaker placement, followed by another prolonged course of antibiotics. 

Discussion: 
This case underscores the challenges of balancing treatment options and addressing patient and family concerns in the context of active IVDU. Treatment noncompliance and relapse pose significant hurdles in addiction management, contributing to recurrent infections and complications. Strategies such as close follow-up, addiction counseling, and multidisciplinary support are crucial in optimizing treatment adherence and outcomes. Successful examples include programs like the Boston Health Care for the Homeless Program and Vermont Hub-and-Spoke Model which integrate medical treatment, addiction counseling, harm reduction strategies, and social support, resulting in improved outcomes like reduced mortality rates, lower reinfection rates, and increased treatment engagement. 

In conclusion, tricuspid endocarditis in the setting of IVDU requires comprehensive care and individualized treatment approaches. The decision between prolonged PO or IV antibiotics should consider factors such as treatment adherence, severity of infection, and close monitoring. Effective management necessitates open communication, shared decision-making, and ongoing support to mitigate treatment noncompliance and relapse risks. Collaboration with community organizations and care coordination are vital for success in providing comprehensive care. It underscores the need for further research, innovative approaches, and enhanced collaboration among healthcare providers, addiction specialists, and support networks to improve outcomes in this challenging patient population.

Tricuspid Endocarditis in the Setting of Active Intravenous Drug Use: Navigating Complexities for Comprehensive Care and Addressing Treatment Challenges

Background
X-linked Creatine Transporter Deficiency (CTD) is caused by pathogenic variants in SLC6A8 and is characterized by intellectual disability, behavioral / developmental disorders, and seizures. The SLC6A8 protein has critical roles in synthesis and distribution of creatine throughout the body. The central nervous system is especially reliant on SLC6A8 to allow creatine to cross the blood brain barrier. Cerebral creatine deficiency disorders are found in up to 2.6% of males with intellectual disability, but few female cases have been reported. Small cohorts have suggested that supplementation of creatine, arginine, and glycine can stop disease progression in males and improve symptoms in females with CTD, though only four females on this therapy have been reported in the medical literature. We offer a case of a female with a de novo pathogenic SLC6A8 variant who significantly improved with supplementation. 

Case Presentation
At time of diagnosis, the reported patient had weight loss, mild intellectual disability, attention deficit hyperactivity disorder, generalized anxiety disorder, and intermittent explosive disorder. Magnetic resonance spectroscopy (MRS) of the brain showed reduced creatine on all acquired spectra. Based on literature review of previously treated female patients, the reported patient was started on creatine-monohydrate at 200 mg/kg/day, L-arginine at 400 mg/kg/day, and L-glycine at 150 mg/kg/day. Within three weeks of starting supplementation, her caregiver reported that she was “doing better in almost every way.” She gained 5 kg and symptom improvement was also seen through her mood: she was sleeping through the night, was more alert during the day, and was showing more appropriate behaviors. After 8 months of supplementation, MRS showed improved creatine concentrations with normalizing semi-quantitative ratios with other brain metabolites. 

Discussion
Previous small cohort studies of male patients with SLC6A8 deficiency demonstrated neither improvement nor decline on treatment. One female supplemented only with creatine showed increased aggression and worsening of self-injurious behaviors. However, two female patients in the literature supplemented with dosages of creatine, arginine, and glycine demonstrated improvement in neuropsychiatric symptoms. The reported patient provides an additional example of a female who responded to supplementation. Females are thought to better respond to supplementation because they are presumed to have at least one partially functioning copy of the SLC6A8 transporter on their second X chromosome, while more severely impacted males are more likely to have no residual transporter function and do not respond to supplementation. Clinicians treating females with CTD should consider treatment with creatine, arginine, and glycine supplementation.

Arginine, Glycine, and Creatine Supplementation Improves Symptoms in a Female with SLC6A8 Creatine Transporter Deficiency

Background:​
Wilson Disease, also called hepatolenticular degeneration, is a rare autosomal recessive mutation of ATP7B, which links copper to ceruloplasmin for elimination. In symptomatic patients, unbound ceruloplasmin is degraded in the bloodstream and free copper deposits in tissues, notably the basal ganglia, kidneys, and cornea. Despite dietary management and copper chelation, it is progressive and incurable, so early identification is key.​
Case Presentation:​
A 68-year-old Caucasian male presented for increasing peripheral neuropathy, myelopathy, and Parkinsonism. Labs revealed serum ceruloplasmin of 5.7 mg/dL; serum copper of 22 ug/dL; normal urine copper. Neurology suggested liver biopsy but his team was reluctant to pursue Wilson given his age and lack of Keyser-Fleischer rings. A second opinion from external neurology suggested copper supplementation, suspecting Menke. A Rowan medical geneticist suggested utilizing 23&Me data for deeper investigation of the ATP7A and ATP7B genes. Visualization of this data through genomic servers showed poor coverage, with sequence gaps and potential mutations of uncertain significance in ATP7A and ATP7B possibly contributing to Menke or Wilson; two mutations in PANK2; and none in ceruloplasmin or other copper metabolic genes. These unsatisfactory 23&Me results prompted the patient to privately obtain 40x whole genome sequencing, which demonstrated a likely pathogenic ATP7B c.3243+1G>A variant, not previously reported, predicted to disrupt a consensus splice site, and a variant of unknown significance, ATP7B c3243+5G>A, previously reported within an intron in Wilson Disease patients. His liver biopsy was fibrosis-negative; quantitative liver tissue copper testing he requested from gastroenterology showed 402 mcg/g dry weight, roughly 8 times the normal level; 250 mcg is diagnostic. He therefore self-referred to the Seattle Children’s Hospital Wilson Disease Center of Excellence, where DAT scan showed decreased radiotracer uptake in right caudate and bilateral right greater than left putamina consistent with Wilson’s Disease or Parkinson’s. He worsened slightly on trientine, but plateaued on zinc. SynOne testing was positive for Parkinson's and moderately improved on carbidopa-levodopa. ​
Discussion:​
Despite being a retired physician living near one of 18 centers for this condition nationwide, he encountered many barriers to diagnosis, followup, and management. Overreliance on pathognomonic signs may have contributed to missing this case. This was the first patient at Rowan-Virtua medical genetics identified for specific testing and follow up based on consumer genetic testing. On 7/11/23, the ATP7B c3243+5G>A allele was reclassified as likely pathogenic. Increased copper accumulation is associated with Parkinsonism.

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Metformin Associated Lactic Acidosis in an Elderly Patient: A Case Report

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Weakness in a patient with spinal cord injury: A broad differential is key