A Guide to Expanding the Use of Buprenorphine Beyond Standard Initiations for Opioid Use Disorder.

Buprenorphine has become an important medication in the context of the ongoing opioid epidemic. However, complex pharmacologic properties and varying government regulations create barriers to its use. This narrative review is intended to facilitate buprenorphine use-including non-traditional initiation methods-by providers ranging from primary care providers to addiction specialists. This article briefly discusses the opioid epidemic and the diagnosis and treatment of opioid use disorder (OUD). We then describe the basic and complex pharmacologic properties of buprenorphine, linking these properties to their clinical implications. We guide readers through the process of initiating buprenorphine in patients using full agonist opioids. As there is no single recommended approach for buprenorphine initiation, we discuss the details, advantages, and disadvantages of the standard, low-dose, bridging-strategy, and naloxone-facilitated initiation techniques. We consider the pharmacology of, and evidence base for, buprenorphine in the treatment of pain, in both OUD and non-OUD patients. Throughout, we address the use of buprenorphine in children and adolescent patients, and we finish with considerations related to the settings of pregnancy and breastfeeding.

Rapid Transition to Buprenorphine in a Patient With Methadone-Related QTc Interval Prolongation.

BACKGROUND: Patients with opioid use disorder (OUD) who are managed on methadone often require transition to buprenorphine therapy. Current recommendations require months to gradually taper off of methadone; however, in some cases, the need to transition is urgent. Only a few rapid methadone-to-buprenorphine transitions have been reported and there are no established protocols to guide clinicians in these cases. CASE PRESENTATION: A 43-year-old man on 95 mg methadone for opioid use disorder experienced cardiac arrest attributable to ventricular fibrillation caused by QTc interval prolongation from methadone. In the hospital, a gradual taper of methadone was initiated but proved intolerable; the patient requested to restart his home dose of methadone and leave against medical advice. A rapid transition was initiated instead. Naltrexone (25 mg) was used to precipitate acute withdrawal followed 1 hour later by a "rescue" with buprenorphine/naloxone (16 mg/4 mg). The Clinical Opiate Withdrawal Score (COWS) peaked at 21 post-naltrexone and fell quickly to 15 within a half-hour of buprenorphine/naloxone administration. The patient was maintained on a total daily dose of 16 mg/4 mg buprenorphine/naloxone through the time of discharge. CONCLUSIONS: A patient requiring an urgent taper off of methadone due to adverse cardiac effects successfully transitioned to buprenorphine/naloxone within 2 hours by using naltrexone to precipitate withdrawal followed by a "rescue" with buprenorphine/naloxone. A relatively high dose of 16 mg/4 mg buprenorphine/naloxone successfully arrested withdrawal symptoms. With further refinement, this protocol may be an important technique for urgent methadone-to-buprenorphine transitions in the inpatient setting.

Myometrial cavernous hemangioma with pulmonary thromboembolism in a post-partum woman: a case report and review of the literature.

INTRODUCTION: Cavernous hemangiomas of the uterus are rare benign vascular lesions. Nine cases of diffuse cavernous hemangioma of the gravid uterus have been reported, most of which diffusely involved the myometrium. These vascular malformations are clinically significant, and may cause pronounced bleeding resulting in maternal or fetal demise. Thrombosis of cavernous hemangiomas of the uterus has been previously reported. We here report the first case in which a thrombosed cavernous hemangioma of the myometrium resulted in a fatal pulmonary embolism in a post-partum woman. CASE PRESENTATION: A 25-year-old obese African-American woman who had one pregnancy and was delivered of twins by cesarean section was admitted 1 week after the successful delivery. The 12-day clinical course included ventilator-dependent respiratory failure, systemic hypertension, methicillin-resistant Staphylococcus aureus in the sputum, leukocytosis and asystole. A transabdominal ultrasound examination showed heterogeneous thickened and irregular products in the endometrial canal. The laboratory values were relevant for an increased prothrombin time, activated partial thromboplastin time, ferritin and a decrease in hemoglobin. The clinical cause of death was cited as acute respiratory distress syndrome. At autopsy, a 400g spongy, hemorrhagic uterus with multiple cystic spaces measuring approximately 0.5 × 0.4cm filled with thrombi within the myometrium was identified. Immunohistological examination with a CD31 stain for vascular endothelium associated antigen confirmed several endothelium-lined vessels, some of which contained thrombi. These histological features were consistent with cavernous hemangioma of the myometrium. A histological examination of the lungs revealed multiple fresh thromboemboli in small- and medium-sized pulmonary arteries in the right upper and lower lobes without organization, but with adjacent areas of fresh hemorrhagic infarction. CONCLUSION: This case underscores the importance of a high index of suspicion in a pregnant or post-partum woman presenting with respiratory symptoms. Thrombosis of the cavernous hemangiomas of the gravid or post-partum uterus is a rare entity. This case is of interest because it indicates that this condition can be fatally complicated by embolization of the thrombi in the cavernous myometrial hemangiomas. Although delivery by conservative methods, as well as cesarean section, is possible without resorting to hysterectomy, occasionally, the consequences could be fatal as in this case.

CHAOS in the mirror: Ballantyne (mirror) syndrome related to congenital high upper airway obstruction syndrome.

In the mirror syndrome, maternal edema mirrors fetal edema. The pathogenesis is unknown. The most common etiologic associations are rhesus isoimmunization, twin-twin transfusion syndrome, and viral infections. Less than 10% of reported cases are associated with congenital anomalies. We report a case due to congenital laryngeal stenosis, which also caused congenital high airway obstruction syndrome (CHAOS), characterized by pulmonary hyperplasia and edema or anasarca, related to airway abnormality. The fetal manifestations of the mirror syndrome and CHAOS overlap, but occurrence of the two in the same patient does not seem to have been reported.

Epicardial coronary artery intimal smooth muscle hyperplasia in a cocaine user.

Accelerated epicardial coronary artery atherosclerosis has been well-documented in cocaine users. There are only two reported cases of cocaine-associated diffuse intimal expansion by proliferated smooth muscle cells causing significant coronary luminal compromise. This type of lesion histologically resembled chronic transplant arteriopathy. Here, we report a third such case.

Fatal gastrointestinal hemorrhage in a paraplegic man with undiagnosed AA (secondary) amyloidosis.

We report a case of a 41-year-old African-American male paraplegic for more than 20 years, who had recurrent infections, renal failure with total urine protein of 840 mg/dL on urine protein electrophoresis and adrenal cortical insufficiency. He died suddenly of massive gastrointestinal (GI) hemorrhage. Autopsy showed clinically undiagnosed systemic amyloidosis involving the kidneys, adrenal cortices, spleen and small blood vessels of most organs and tissues, including those of the gastrointestinal tract. The history and autopsy findings indicated secondary or amyloid A (AA) amyloidosis. Paraplegia was one of the most common causes of secondary amyloidosis decades ago, but has now become unusual in patients with AA amyloidosis. Extensive involvement of GI small vessels was the most likely cause of fatal bleeding. GI amyloid previously has been shown to cause hemorrhage, but a fatal case has not yet been described.

Pulmonary tumor embolism.

A 36-year-old woman with breast cancer was admitted with shortness of breath. A computed tomography angiogram was obtained and was negative for pulmonary embolism. She quickly developed hypoxemic respiratory failure and was transferred to the intensive care unit. She appeared to be improving when she suffered sudden cardiac death. Autopsy showed extensive lymphatic and vascular tumor emboli, which were the immediate cause of death. Tumor emboli are rarely diagnosed before death but seem to be more common than realized. It is important to recognize this entity, because there have been some case reports of cure. The usual mechanism of death is progressive right heart failure; sudden death from tumor embolism has rarely been described.

Human myocardial cell lines generated with SV40 temperature-sensitive mutant tsA58.

Conditionally transformed human myocardial cell lines would be a valuable resource for studying human cardiac cell biology. We generated clonal human fetal cardiocyte cell lines by transfection of fetal ventricular cardiac cell clones with a plasmid containing a replication-defective mutant of the temperature-sensitive SV40 strain tsA58. Multiple resulting cell lines showed similar features, namely: (1) T antigen (TAg) expression at both permissive (34 degrees C) and restrictive (40.5 degrees C) temperatures; (2) extended growth capacity in comparison with parental wild type, when grown at the permissive temperature; (3) both temperature-dependent and serum-responsive growth, and; (4) an incompletely differentiated fetal phenotype which was similar at both permissive and restrictive temperatures and in the presence and absence of serum. The transformed myocyte phenotype was demonstrated using immunocytochemistry, Western and Northern blotting, and reverse transcription-polymerase chain reaction (RT-PCR). Cell lines expressed skeletal alpha-actin, atrial natriuretic peptide (ANP), and keratins, but no sarcomeric myosin heavy chain or desmin. Immunoreactive sarcomeric actin was expressed predominantly as a truncated protein of approximately 38 kD. The phenotype of the transformed cells differs from that of the wild-type parental cells as well as from those reported by others who have used TAg to immortalize rodent or human ventricular myocytes. Our cell lines should provide a useful tool for study of the molecular mechanisms regulating growth and differentiation in human cardiac muscle cells.