Leptomeningeal carcinomatosis (LC) is a rare leptomeningeal spread of diffusely metastatic tumors. It occurs more commonly with hematologic tumors, less commonly with solid tumors, and is exceedingly rare in prostate cancer. Due to its scarcity, it has traditionally been difficult to diagnose LC but advancement of MRI has helped considerably. However, even with technological improvements, pre-mortem diagnosis of LC remains difficult and controversial. Our case is a 71-year-old male with prostate cancer with bone metastases who presented to our facility with altered mental status (AMS), lower extremity weakness, and worsening diarrhea. The diarrhea was responsive to antibiotic therapy, but his AMS did not resolve. A head CT without contrast was negative but follow-up brain MRI revealed leptomeningeal enhancement highly suggestive of LC. Cerebrospinal fluid (CSF) cytology results were negative and other CSF studies were inconclusive. Although further studies were planned, the patient continued to deteriorate, and the family elected to withdraw care. He passed away without beginning treatment for the LC. Despite advances in cancer therapies, LC remains difficult to diagnose and treat. Imaging may be suggestive of the condition but the confirmatory tests such as repeated CSF cytology or meningeal biopsy are not only invasive but also usually occur postmortem. Additional methods of CSF testing have been studied to evaluate their role in accurately diagnosing LC but low specificity for LC has somewhat limited their use. Although treatment options are mainly palliative in nature, prompt recognition and early treatment could grant valuable time for patients and families.

Background The safety of ProHeart® 12 (PH 12; extended-release injectable suspension; 10% moxidectin in glyceryl tristearate microspheres) was evaluated in four studies using Beagle dogs and one study using ivermectin-sensitive Collies. The recommended dose is 0.5 mg/kg subcutaneously once yearly. Methods Study 1: safety margin was evaluated as 3 treatments of PH 12 (0× (control); 1× (recommended dose); 3× (3 times recommended dose) and 5× (5 times recommended dose) in 12 months via clinical observations, body weights, food consumption, injection site observations, physical examinations, moxidectin tissue assay, pharmacokinetics, and clinical and anatomic pathology. Study 2: safety in breeding-age males was demonstrated by semen testing at 14-day intervals from Day 7 to Day 91 post-treatment (0× or 3×). Study 3: reproductive safety in females was demonstrated by monitoring dams and litters following treatments (0× or 3×) administered during breeding, gestation, or lactation. Study 4: safety in dogs surgically implanted with adult heartworms was evaluated by clinical and laboratory monitoring following treatment with 0× or 3× administered 61 days post-implantation. Study 5: safety in ivermectin-sensitive dogs (120 µg/kg SC) was by clinical monitoring for 1 week after administering 1×, 3× or 5×. Results Study 1: slight swelling clinically detectable at some 3× and 5× injection sites was characterized microscopically as granulomatous inflammation, like tissue responses to medical implants, interpreted as non-adverse. Pharmacokinetics were dose-proportional and there was little or no systemic accumulation. Residual moxidectin mean (range) at 1× injection sites after 1 year was 16.0% (0.045–37.6%) of the administered mass. Studies 2 and 3: no effects were identified in reproductive indices (females) or semen quality characteristics (males). Study 4: PH 12 produced marked reductions in circulating microfilariae and lower numbers of adult heartworms, but no adverse clinical signs were identified. Study 5: there were no abnormal clinical signs at 1×, 3× or 5× overdoses of PH 12 in ivermectin-sensitive dogs. Conclusions PH 12 has a > 5× safety margin in both normal and ivermectin-sensitive dogs, has no effects on canine reproduction, and is well tolerated in heartworm-positive dogs. The only treatment-related finding was non-adverse, granulomatous inflammation at the injection site.

Human Herpesvirus 6 (HHV-6) is a virus known to cause mild infection in children. In adults, HHV-6 reactivation has been described in immunocompromised individuals.Rarely, viral reactivation occurs in immunocompetent adults causing significant disease and morbidity. The use of certain medications, like amoxicillin, has been found to induce HHV-6 reaction in a number of cases. We report a 63-year-old immunocompetent female who presented with headache, fever and altered mental status. Past medical history included two bouts of HHV-6 encephalitis treated at external facilities. According to her medical history, both episodes of encephalitis were preceded by amoxicillin use. Her lumbar puncture analysis was consistent with viral etiology and a cerebrospinal fluid (CSF) PCR was positive for HHV-6. She was successfully treated with intravenous ganciclovir. It is important to keep a broad differential diagnosis in mind when approaching encephalitis in adults, and to be aware of unusual triggers for viral reactivation. Clinicians who suspect the infection in the correct clinical setting can successfully treat patients with recurrent HHV-6.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a potentially fatal severe adverse reaction to medications. Numerous drugs have been implicated, with carbamazepine and allopurinol being the most common. Tenofovir-induced DRESS is extremely rare. We report a case of a 65-year-old male patient with a diffuse exfoliative maculopapular rash across his entire body of five weeks of duration. The patient also had icteric sclera, abnormal liver enzymes and Raynaud’s of the tongue, nose and the left fifth finger. After discontinuation of tenofovir, the case resolved over a span of ten days. A high index of suspicion is crucial along with the prompt withdrawal of the offending medication for a good outcome.

BackgroundNeutropenic enterocolitis is a life-threatening inflammation of the colon with a mortality rate above 50% primarily seen in neutropenic patients on cytotoxic chemotherapy. The following cases illustrate three patients with this condition following midostaurin administration after standard induction chemotherapy with daunorubicin/idrarubicin and cytarabine for acute myeloid leukemia (AML). Midostaurin is a multitargeted FMS-Like Tyrosine kinase 3 (FLT3) receptor inhibitor used in AML treatment after induction chemotherapy.MethodsReview of records of three patients seen by the infectious disease service.ResultsIn these cases, patients were diagnosed with AML with FLT3 mutation. All three were admitted and started on standard induction chemotherapy. Midostaurin was started on chemotherapy day 8 at which time all patients were neutropenic. The patients developed fevers, abdominal pain, and diarrhea within 36 hours of starting midostaurin and had abdominal CT findings consistent with neutropenic enterocolitis. For two patients, midostaurin was discontinued and symptoms improved upon discontinuation. One patient completed the course of midostaurin with symptom resolution after its completion. Of note, all were started on appropriate prophylactic antibiotics at chemotherapy initiation and were started on broad-spectrum antibiotics at onset of fevers and abdominal symptoms. Appropriate evaluation was also done for each patient to rule out other causes of abdominal symptoms, including testing for Clostridium difficile colitis.ConclusionThese cases are significant because they illustrate individuals treated with standard induction chemotherapy for AML and started on midostaurin while neutropenic who began reporting symptoms of neutropenic enterocolitis within 36 hours of receiving midostaurin. This shows a possible increased toxicity when midostaurin is given after induction chemotherapy in the setting of neutropenia. Stone et al. showed increased intestinal symptoms with midostaurin, but no cases of neutropenic enterocolitis have been reported. With increased midostaurin use in the past year, further studies are warranted to establish and raise awareness of a possible direct association between midostaurin and gastrointestinal toxicity.Disclosures All authors: No reported disclosures.