Lokesh Shahani

Cognitive impairment in men with testicular cancer prior to adjuvant therapy.

Cognitive dysfunction experienced by individuals with cancer represents an important survivorship issue because of its potential to affect occupational, scholastic, and social activities. Whereas early efforts to characterize cognitive dysfunction primarily focused on the effects of chemotherapy, more recent evidence indicates that impairment may exist before systemic treatment. This study characterized cognitive dysfunction before adjuvant chemotherapy in a sample of men diagnosed with nonseminomatous germ cell tumors (NSGCT) of the testis.

Neurocognitive deficits increase risk of poor retention in care among older adults with newly diagnosed HIV infection.

Objective:To evaluate the role of neurocognitive impairment on retention in care across the lifespan in antiretroviral-naïve persons newly diagnosed with HIV. Design:A prospective observational study of 138 antiretroviral-naive newly diagnosed HIV-positive participants who presented to an urban clinic between August 2010 and April 2013. Methods:All participants underwent a baseline evaluation that included a neuromedical examination and brief neuropsychological test battery. Retention in care was operationalized as attending at least two visits separated by more than 90 days during the 12-month follow-up period. Results:Fifty-five per cent of participants were retained in care over the study observation period. In a logistic regression controlling for ethnicity, there was a significant interaction between age and neurocognitive impairment in predicting retention in care (P = 0.009). Planned post-hoc analyses showed that neurocognitive impairment was associated with a significantly lower likelihood of retention in care among participants aged 50 years and older (P = .007), but not among younger participants (P > 0.05). Conclusion:Extending prior research on antiretroviral adherence and medication management, findings from this study indicate that neurocognitive impairment may be an especially salient risk factor for poor retention in care among older adults with newly diagnosed HIV infection.

Refractory calcinosis in a patient with dermatomyositis: response to intravenous immune globulin

Dermatomyositis is an inflammatory myopathy and commonly presents with progressive, symmetric proximal muscle weakness and cutaneous findings. Calcinosis is a severe manifestation that can be debilitating. The cutaneous manifestations of dermatomyositis may also develop in the absence of detectable muscle disease, and can persist after the successful treatment of myositis. The author reports a 30-year-old woman with biopsy-proven dermatomyositis who had failed previous trials of azathioprine and methotrexate. Her muscle weakness was controlled with mycophenolate mofetil and prednisone; however, she had recurrent attacks of painful calcinosis. The patient responded to intravenous immune globulin (IVIG) along with intravenous methylprednisone, followed by IVIG for 2 consecutive days each month. This regimen has been effective in preventing recurrence of her calcinosis. This case illustrates the cutaneous manifestation of dermatomyositis, which is often more refractory to treat as compared to the muscle involvement and require additional approaches such as IVIG.

Tramadol Precipitating Serotonin Syndrome in a Patient on Antidepressants

To the Editor: Tramadol is a synthetic analog of codeine. It is a commonly prescribed analgesic because of its relatively lower risk of addiction and better safety profile as compared with other opiates. Its action is mainly targeted at the central m-opioid receptors; however, it also inhibits serotonin and norepinephrine reuptake at the peripheral level. It is structurally similar to venlafaxine and accounts for a significant number of drug interactions among patients using antidepressants. We report a 62-year-old Caucasian man with a major depressive episode currently in partial remission on citalopram 40 mg and bupropion 150 mg twice a day. The patient had a recent visit with his primary care physician and was started on tramadol 50 mg three times a day for musculoskeletal pain. Three day after being started on tramadol, the patient presented to the emergency department with tremors, diaphoresis, and anxiety. He denied excessive use of any of his medication and denied any recent illicit drug use. Further examination revealed tachycardia, elevated blood pressure, and presence of clonus in the lower extremities. The patient was diagnosed with serotonin syndrome based on the triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. He was admitted to the intermediate care unit for further monitoring. Medications, including citalopram, bupropion, and tramadol, were discontinued, and supportive care was provided. Diazepam was used to help with anxiety, and labetolol was used to reduce the patient’s autonomic instability. The symptoms resolved within 48 hours of admission. Antidepressant medications were restarted at a lower dose and titrated in outpatient care. The primary care physician was educated about the drug interaction, and an alternative analgesic medication was used in the future for this patient. Serotonin toxicity has been traditionally seen with high doses of serotonergic antidepressants or their combination. However various proserotonergic drugs have been implicated in serotonin syndrome if used along with antidepressants, especially in older patients. Tramadol is O-methylated by CYP2D6, and SSRIs are known to have an inhibitory effect on CYP2D6. This interaction could be responsible for a reduction in tramadol metabolism, leading to the serotonin toxicity seen in our patient. Physicians should be aware and educate patients on the risk of serotonin toxicity secondary to drug interactions with various psychotropic medications.

Steroid unresponsive anti-NMDA receptor encephalitis during pregnancy successfully treated with plasmapheresis

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is an autoimmune disorder resulting in neurological and psychiatric symptoms. It is rare during pregnancy and treatment is extremely challenging as little data exist to guide management. A 26-year-old woman presented at 22 weeks of gestation with intermittent headache and an acute episode of bizarre behaviour and grandiose delusions resulting in hospitalisation. The patient was worked up for encephalitis and was found to have anti-NMDA receptor antibody in cerebrospinal fluid as well as in serum. She was initially treated with high-dose steroids but failed to improve clinically and serologically. She was then treated with plasmapheresis and showed clinical and serological response. She had a successful delivery at 37 weeks and the baby did not show serological evidence of disease. This case adds to the sparse literature of anti-NMDA receptor encephalitis during pregnancy and adds to the differential diagnosis of new onset psychiatric symptoms during pregnancy.

Intravenous immunoglobulin in treatment of Clostridium difficile colitis.

Clostridium difficile infection is the most common infectious cause of healthcare-acquired diarrhoea. Severe infections cause therapeutic challenges for healthcare providers. Various novel treatment modalities are currently being explored for treatment of severe disease. The authors report a 70-year-old female who presented to the emergency room with 1 week history of fever, watery diarrhoea, diffuse abdominal pain and weakness. C difficile toxin was detected in the stool and abdominal CAT scan showed extensive colonic wall thickening. The patient was started on intravenous metronidazole along with oral vancomycin. Due to the severity of the infection the patient was given intravenous immunoglobin for 4 consecutive days. The patient had vast improvement in her clinical symptoms with resolution of the multi-organ system failure. It is currently considered that the predominant intravenous immunoglobin’s mechanism of action is through binding and neutralisation of toxin A by IgG antitoxin A antibodies.

Fusobacterium necrophorum - Beyond Lemierres syndrome

Fusobacterium necrophorum is a non-sporulating anaerobic gram negative bacillus and has traditionally been associated with Lemierre’s syndrome. The authors report a 34-year-old male who presented to the emergency department with a week’s history of dull epigastirc pain. Significant medical history included chronic pancreatitis secondary to alcohol use. The patient had radiological evidence of acute on chronic pancreatitis with thrombosis of the portal vein and multiple intrahepatic abscesses. CT-guided drainage of left upper quadrant revealed fluid collection in the pancreatic bed. The fluid culture grew F necrophorum and the patient was treated with tigecycline for 4 weeks. The patient improved symptomatically and his follow-up computerised axial tomography scan 2 months later showed resolving liver abscess, cavernous transformation of the portal vein and stable findings of chronic pancreatitis. This could represent an infection of the peripancreatic tissue with F necrophorum further leading to pylephlebitis.

Assessing efficacy of a retention-in-care intervention among HIV patients with depression, anxiety, heavy alcohol consumption and illicit drug use.

Objective:We evaluated whether heavy alcohol use, illicit drug use or high levels of anxiety, and depression symptoms were modifiers of the retention through enhanced personal contact intervention. The intervention had previously demonstrated overall efficacy in the parent study. Design:Randomized trial. Methods:A total of 1838 patients from six US HIV clinics were enrolled into a randomized trial in which intervention patients received an ‘enhanced contact’ protocol for 12 months. All participants completed an audio computer-assisted self-interview that measured depression and anxiety symptoms from the Brief Symptom Inventory, alcohol use from the Alcohol Use Disorders Identification Test-Consumption instrument, and drug use from the WHO (Alcohol, Smoking and Substance Involvement Screening Test) questions. The 12-month binary outcome was completing an HIV primary care visit in three consecutive 4-month intervals. The outcome was compared between intervention and standard of care patients within subgroups on the effect modifier variables using log-binomial regression models. Results:Persons with high levels of anxiety or depression symptoms and those reporting illicit drug use, or heavy alcohol consumption had no response to the intervention. Patients without these ‘higher risk’ characteristics responded significantly to the intervention. Further analysis revealed higher risk patients were less likely to have successfully received the telephone contact component of the intervention. Among higher risk patients who did successfully receive this component, the intervention effect was significant. Conclusion:Our findings suggest that clinic-based retention-in-care interventions are able to have significant effects on HIV patients with common behavioral health issues, but the design of those interventions should assure successful delivery of intervention components to increase effectiveness.

Intraventricular Taenia solium Cysts Presenting with Bruns Syndrome and Indications for Emergent Neurosurgery

Bruns syndrome is an unusual phenomenon, characterized by attacks of sudden and severe headache, vomiting, and vertigo, triggered by abrupt movement of the head. The presumptive cause of Bruns syndrome is a mobile deformable intraventricular mass leading to an episodic obstructive hydrocephalus. Intraventricular tumors have been associated with Bruns syndrome; however, few cases of intraventricular neurocysticercosis have been reported to present with Bruns syndrome. We report the first series of fourth ventricular neurocysticercosis presenting with Bruns syndrome in the United States and review the other published cases where surgery was indicated.

Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome

Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement in a previously incompetent human immune system manifesting as worsening of clinical symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory response. IRIS was first recognized in the setting of human immunodeficiency virus, and this clinical setting continues to be where it is most frequently encountered. Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and the underlying pathogen, include excessive activation of the immune system, with increased circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening for opportunistic infections before starting ART is a key element to prevent this phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome and exclusion of alternative diagnoses, particularly underlying infections and drug resistance. Controlled studies supporting the use of pharmacologic interventions in IRIS are scare, and recommendations are based on case series and expert opinions. The only controlled trial published to date, showed reduction in morbidity in patients with paradoxical tuberculosis-related IRIS with the use of oral corticosteroids. There are currently limited data to recommend other anti-inflammatory or immunomodulatory therapies that are discussed in this review, and further research is needed. Ongoing research regarding the immune pathogenesis of IRIS will likely direct future rational therapeutic approaches and clinical trials.