The Role of Depressive Symptoms in Substance Use Among African American Boys Exposed to Community Violence

Adolescents exposed to community violence (CV) are at increased risk for alcohol, marijuana, and tobacco use. The disproportionate exposure to CV among African American boys heightens their susceptibility to substance use and related problems. Depressive symptoms are linked to both CV exposure and adolescent substance use; however, their role in the link between CV exposure and substance use in African American male adolescents has received little attention. The current study examined whether depressive symptoms mediate or moderate the associations between CV exposure and substance use among African American male adolescents. Participants were 225 African American adolescent boys in Baltimore, Maryland who completed measures of CV exposure and depressive symptoms in 10th grade and measures of substance use in 10th and 11th grades. Hierarchal linear regression analyses indicated that depressive symptoms moderated associations between violent victimization and alcohol and tobacco use, R² = .21–.30, ps < .001. There was a positive association between CV victimization and alcohol and tobacco use among those who reported high levels of depressive symptoms but not low levels. Depressive symptoms also moderated the link between witnessing CV and alcohol use such that witnessing CV was negatively related to alcohol use among those who reported high levels of depressive symptoms only. The findings suggest that depressive symptoms may play an important role in differentiating alcohol and tobacco use outcomes in CV-exposed African American boys. Prevention efforts should assess for depressive symptoms to identify adolescent boys with the highest risk of substance use.     

Sirolimus-associated diffuse alveolar hemorrhage

Sirolimus is an immunosuppressive medication used in transplant recipients. To our knowledge, we describe the third reported case of alveolar hemorrhage in association with sirolimus. Fever, dyspnea, hemoptysis, and lung infiltrates resolved rapidly with cessation of sirolimus therapy both initially and after reinstitution of the drug. Unlike previous reports, our patient had no evidence of lymphocytic alveolitis but rather marked macrophage hemosiderosis, suggesting that sirolimus pulmonary toxicity may manifest through 2 separate mechanisms. Our case highlights an uncommon but potentially lethal manifestation of sirolimus pulmonary toxicity.     

Comparison of Current Recommended Regimens of Atropinization in Organophosphate Poisoning

Atropine is the mainstay of therapy in organophosphate (OP) toxicity, though research and consensus on dosing is lacking. In 2004, as reported by Eddleston et al. (J Toxicol Clin Toxicol 42(6):865-75, 2004), they noted variation in recommended regimens. We assessed revisions of original references, additional citations, and electronic sources to determine the current variability in atropine dosing recommendations. Updated editions of references from Eddleston et al.’s work, texts of Internal and Emergency Medicine, and electronic resources were reviewed for atropine dosing recommendations. For comparison, recommendations were assessed using the same mean dose (23.4 mg) and the highest dose (75 mg) of atropine as used in the original paper. Recommendations were also compared with the dosing regimen from the World Health Organization (WHO). Thirteen of the original recommendations were updated and 15 additional references were added giving a convenience sample of 28. Sufficient information to calculate time to targeted dose was provided by 24 of these samples. Compared to 2004, current recommendations have greatly increased the speed of atropinization with 13/24 able to reach the mean and high atropine dose within 30 min compared to 1/36 in 2004. In 2004, there were 13 regimens where the maximum time to reach 75 mg was over 18 h, whereas now, there are 2. While only one recommendation called for doubling the dose for faster escalation in 2004, 15 of the 24 current works include dose doubling. In 2004, Eddleston et al. called for an evidence-based guideline for the treatment of OP poisoning that could be disseminated worldwide. Many current recommendations can adequately treat patients within 1 h. While the WHO recommendations remain slow to treat patients with OP poisoning, other authorities are close to a consensus on rapid atropinization.     

Location of Lymph Node Involvement in Patients with Esophageal Adenocarcinoma Predicts Survival

Background

The location of positive lymph nodes has been abandoned in the seventh classification of the TNM staging system for esophageal adenocarcinoma. The present study evaluates whether distribution of involved nodes relative to the diaphragm in addition to TNM 7 further refines prediction.

Methods

Pathology reports of patients who underwent esophagectomy between 2000 and 2008 for adenocarcinoma of the esophagus were reviewed and staging was performed according to the seventh UICC-AJCC staging system. In addition, lymph node involvement of nodal stations above and below the diaphragm was investigated by endoscopic ultrasonography (EUS) in a separate cohort of patients who were scheduled for esophagectomy between 2008 and 2009 at two institutions. Survival was calculated by the Kaplan–Meier method, and multivariate analysis was performed with a Cox regression model.

Results

Some 327 patients who had undergone esophagectomy for cancer were included. Multivariate analysis revealed that patients with from three to six involved lymph nodes in the resection specimen on both sides of the diaphragm had a twofold higher chance of dying compared to patients with the same number of involved lymph nodes on one side of the diaphragm. EUS assessment of lymph node metastases relative to the diaphragm in 102 patients showed that nodal involvement on both sides of the diaphragm was associated with worse survival than when nodes on one side or no nodes are involved [HR (95 % CI) 2.38 (1.15–4.90)].

Conclusions

A combined staging system that incorporates distribution of lymph nodes relative to the diaphragm refines prognostication after esophagectomy as assessed in the resected specimen and pretreatment as assessed by EUS. This improved staging has the potential to have a great impact on clinical decision making as to whether to embark upon potentially curative or palliative treatments.     

Cisplatin inhibits bone healing during distraction osteogenesis

Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non‐cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five‐dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five‐dose CDP regimen were observed in TNFR1KO mice. The two‐dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri‐operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:464–470, 2014.     

Refractory Heart Failure Dependent on Short‐Term Mechanical Circulatory Support: What Next? Heart Transplant or Long‐Term Ventricular Assist Device

Chronic heart failure is a progressive and eventually fatal illness. Although the disease cannot be cured and treatment is symptom oriented, most of the patients benefit from optimum medical treatment. Patients with rapid deterioration in chronic advanced heart failure refractory to medical treatment need inotropic support and may need intra‐aortic balloon pump to maintain circulatory support, which of course cannot be prolonged beyond a certain limit. The outcome of heart transplant and long‐term ventricular assist device (VAD) in such patients is poor. The short‐term mechanical circulatory support (MCS) offered to such patients not only provides effective circulatory support and stabilizes them hemodynamically, but also halts the ensuing or reverts the established end‐organ failure. As the name suggests, the short‐term MCS offers support for the short term, usually less than a month. Although some patients with acute heart failure experience recovery of myocardial function with short‐term MCS support, others become dependent. These patients, stabilized and “stuck” with short‐term MCS, can be “rescued” with long‐term VAD or heart transplantation. Both the procedures, when done in this special situation, have their inherent advantages, disadvantages, and complications and hence need the careful consideration about the choice of the procedure. We have tried to elucidate this situation by considering the advantages and disadvantages of both options.