Thalidomide as "salvage" therapy for patients with delayed hypersensitivity response to infliximab: a case series

Infliximab is efficacious for refractory Crohn's disease, but delayed hypersensitivity reactions preclude retreatment for patients experiencing this complication. We report the results of four patients offered enrollment in an open label trial of thalidomide as "salvage" therapy for their refractory disease. Two patients with active fistulous disease and two with lumenal disease received open-label thalidomide 200 mg every night and were evaluated monthly at the University of Chicago Clinical Research Center for 12 weeks. Before administration, patients signed an informed consent form discussing the potential risks of thalidomide use. Female patients of child-bearing age underwent serum pregnancy testing every 4 weeks. Response was defined as an absolute decrease in Crohn's Disease Activity Index (CDAI) by 100 points or improvement in two of three clinical parameters for fistulous disease. A patient with a single perirectal fistula had complete closure by 4 weeks, the other had noticeable improvement of five perianal fistulae at 4 weeks and complete closure by 12 weeks. One lumenal patient had a CDAI decrease of 250 points in 4 weeks. The fourth patient withdrew secondary to sedation after only a week of therapy. Two patients (one fistula, one lumenal) continued thalidomide past the 3-month study period and remained in remission at 5 and 7 months. Side effects reported were sedation (four of four patients), hypertension (one of four), and peripheral neuropathy (one of four). Thalidomide appears to be a safe and effective alternative for short-term healing in patients who develop infliximab-induced delayed hypersensitivity reaction and may be an alternative strategy for those at risk.     

Cyclosporin treatment for aplastic anemia: A case report demonstrating a second response to second exposure to cyclosporin

Cyclosporin has been used in the treatment of aplastic anemia, often in combination with other drugs, making it difficult to make a clear distinction between the effects of cyclosporin and those of other treatments. This report demonstrates a clear response of a patient with aplastic anemia to single drug cyclosporin therapy.     

Dapsone induced cholangitis as a part of dapsone syndrome: a case report

Background

Dapsone can rarely cause a hypersensitivity reaction called dapsone syndrome, consisting of fever, hepatitis, exfoliative dermatitis, lymphadenopathy and hemolytic anemia. Dapsone syndrome is a manifestation of the DRESS (drug rash with eosinophilia and systemic symptoms) syndrome which is a serious condition that has been reported in association with various drugs. Cholangitis in dapsone syndrome has not been reported so far in the world literature.

Case presentation

We report a patient who presented with fever, exfoliative dermatitis, jaundice and anemia within three weeks of starting of dapsone therapy. These features are typical of dapsone syndrome, which is due to dapsone hypersensitivity and is potentially fatal. Unlike previous reports of hepatitic or cholestatic injury in dapsone syndrome we report here a case that had cholangitic liver injury. It responded to corticosteroids.

Conclusion

We conclude that cholangitis, though unusual, can also form a part of dapsone syndrome. Physicians should be aware of this unusual picture of potentially fatal dapsone syndrome.

     

Visceral leishmaniasis mimicking as second line anti retroviral therapy failure

Visceral leishmaniasis (VL) has increased as a complicating infection in subjects with human immunodeficiency virus (HIV) in developing countries. Both infections tend to lower the cell-mediated immunity resulting in poor drug response. In HIV-positive subjects the clinical course as well as organ involvement of VL simulates tuberculosis, another very common tropical infection. We present a case of VL/HIV co-infection where the individual failed to respond to first and second line antiretroviral therapy with persistently low CD4 counts. This patient was also subjected empirically to antitubercular therapy with no clinical improvement; he was finally diagnosed as a case of VL in HIV upon revelation of amastigotes in bone marrow despite the initial negative serology on two occasions. He showed dramatic improvement in CD4 counts and clinical status on Amphotericin B therapy. In endemic areas and in HIV positive subjects a systemic and careful parasitology follow-up is necessary to ensure that no clinical form of leishmaniasis is overlooked.     

Endoscopic vacuum therapy for post-esophagectomy anastomotic dehiscence as rescue treatment: a single center case series

Esophagus - Endoscopic vacuum therapy (EVT) represents an effective endoscopic technique for the treatment of post-esophagectomy leaks and can be used after failure of primary treatment. We aimed...     

Failure to achieve a major cytogenetic response by 12 months defines inadequate response in patients receiving nilotinib or dasatinib as second or subsequent line therapy for chronic myeloid leukemia

To determine when patients with incomplete responses on second-line tyrosine kinase inhibitor (2TKI) therapy should consider alternative treatment, we analyzed the outcome of 113 patients receiving nilotinib (n = 43) or dasatinib (n = 70) after imatinib failure. After 12 months of 2TKI therapy, patients achieving a major cytogenetic response (12MMCyR) had a significant survival advantage over patients in minor cytogenetic response or complete hematologic response, with a projected one-year survival of 97% and 84% respectively (P = .02). Projected 1-year progression to hematologic failure, accelerated phase, or blast phase was also significantly different (3% vs 17%, P = .003). Early cytogenetic response was strongly predictive of achievement of 12MMCyR, with less than 10% of patients showing no cytogenetic response at 3 to 6 months eventually attaining the target of 12MMCyR. These results suggest that patients receiving 2TKI with no cytogenetic response at 3 to 6 months should be considered for alternative therapies.     

Sulfonylureas as second line therapy for type 2 diabetes among veterans: Results from a National Longitudinal Cohort Study

AimsTo assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone.Materials and MethodsThis was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes.ResultsSwitching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7–19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively).ConclusionsSwitching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy.     

Exposure to radiotherapy for first primary cancer as a risk factor for second primary thyroid cancer: A case-control study

BackgroundSecond primary neoplasms are associated with high mortality and morbidity rates in cancer survivors successfully treated for the first malignancy. Studies suggested an association between the type of first neoplasm and risk of subsequent thyroid cancer, with part of this risk attributable to exposure to radiotherapy during treatment of the first primary tumor. This study aimed to determine whether radiotherapy is a risk factor for thyroid cancer in patients previously treated for another neoplasm.MethodsThis retrospective case-control study included patients diagnosed with their first cancer between 2007 and 2017. Patients who subsequently developed thyroid cancer as a second primary neoplasm were defined as “cases”, and patients who did not develop a second cancer were defined as “controls”. Exposure to radiotherapy was the primary risk factor of interest; other risk factors were the site to which radiotherapy was delivered and the first neoplasm type.ResultsExposure to radiotherapy was associated with an increased risk of thyroid cancer (odds ratio [OR] = 2.410, 95% confidence interval [CI]: 1.219–4.764), in particular, in women (OR = 3.121, 95% CI: 1.232–7.907) and in patients receiving radiotherapy to the thorax (OR = 6.298, 95% CI: 2.581–15.370). The median survival time from first cancer recovery to thyroid cancer occurrence was 63.80 months; there was no difference in survival between patients who did and did not receive radiotherapy (P = 0.899).ConclusionRadiation to the thorax can increase the risk of thyroid cancer as a second neoplasm among patients with cancer successfully treated for their first cancer.     

Capecitabine therapy for refractory metastatic thyroid carcinoma: a case series.

Objective: There are few effective therapies for metastatic medullary (MTC) or radioiodine-resistant follicular thyroid carcinomas (FTC). We report a single institution's experience with capecitabine, a thymidylate synthase (TS) inhibitor, in the treatment of MTC and FTC. Design: We retrospectively analyzed five cases of metastatic thyroid carcinoma, three MTCs and two radioiodine-resistant FTCs, treated with capecitabine alone or in combination with other chemotherapeutics. Patients were selected for treatment based on low tumor TS immunohistochemical staining (相似文献   

The use of low-dose etanercept as an alternative therapy for treatment of ankylosing spondylitis: a case series

During recent decades, biological medications play a crucial role for treating rheumatologic disorders and thus are strongly recommended for initial treatment of ankylosing spondylitis. However, because of high cost of biological drugs, the use of these drugs has been limited. In current series, we tried to assess safety of low-dose etanercept as a common usable biological drug in patients with ankylosing spondylitis. In a case-series study, 4 men with ankylosing spondylitis were treated with low-dose Etanercept (25?mg/2?weeks) plus methotrexate (10?mg/week). Safety was assessed by measuring rate of differences in severity of clinical manifestations and level of C-reactive protein (CRP). After the completion of treatment with low-dose etanercept, inflammatory low back pain and morning stiffness was reduced lower than 30?min in all patients. Only one patient had baseline high serum ESR and positive CRP that was changed to negative following treatment protocol. At one-year follow-up, all participants continued their regular treatment regimen with the etanercept survival rate 100%. Neither side effects related to drug nor clinical complications were observed within the follow-up period. Our findings suggest that low-dose etanercept (25?mg/2?weeks) has an acceptable safety and effectiveness profile in individuals with ankylosing spondylitis and can be good alternative instead of conventional therapy with etanercept (25?mg two times per week).     

Response to fludarabine in B-cell chronic lymphocytic leukemia patients previously treated with chlorambucil as up-front therapy and a CHOP-like regimen as second line therapy.

BACKGROUND AND OBJECTIVES: Fludarabine (FAMP) is the most active single agent in relapsed and refractory patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear whether it should be used immediatly after failure of chlorambucil (CLB). We addressed such an issue retrospectively analyzing a series of patients in whom FAMP was used as third-line therapy after a sequential use of CLB and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimen, respectively. DESIGN AND METHODS: On a retrospective basis, 57 B-CLL patients fulfilling the above mentioned criteria and followed-up in seven different hematologic institutions, were evaluated. RESULTS: Of 57 patients who were evaluated for response, 3 (5.2%) achieved a complete response (CR), 30 (52.6%) had a partial response (PR) and the remaining 24 (42.1%) failed to respond to FAMP. Overall median survival from the start of FAMP therapy was 30 months. Survival by tumor response did not show any difference between responders and non-responders (p = 0.536). The survival was significantly shorter in the group of patients with progressive disease than in all other patients included in our study (p = 0.05). Using each patient as his own control (McNemar test) we attempted to evaluate the value of FAMP in inducing a therapeutic response after failure of previous therapies. Among the 37 patients resistant to CLB the response rate was 40.3% with FAMP (p = 0.037) and only 17.5% with CHOP (p = 1.0). Among 35 patients resistant to a CHOP-like regimen, the response rate was 29.8% (p = 0.066) after FAMP therapy. INTERPRETATION AND CONCLUSIONS: From our results, it seems that FAMP works better than a CHOP-like regimen in patients resistant to CLB although results do not translate into a survival advantage for responders.     

Thoracoscopic decortication as first-line therapy for pediatric parapneumonic empyema. A case series

STUDY OBJECTIVES: Previous articles have promoted the early use of thoracotomy and decortication for refractory empyema. This study examines thoracoscopy and decortication at the time of initial chest tube placement in pediatric patients with parapneumonic empyema. DESIGN: We reviewed the medical records of 16 consecutive patients who were children with parapneumonic empyema. RESULTS: Thirteen children (group 1) underwent thoracoscopic decortication and tube thoracostomy as their initial operative procedures; 3 children (group 2) had tube thoracostomy alone. In both groups, chest tubes were removed prior to their discharge to home. The mean (+/- SD) operative time for thoracoscopy was 81 +/- 19 min with no complications. On average, chest tubes were removed by postoperative day 4. The mean time to discharge was 8.3 days. Two children eventually required lobectomy. The mean operative time for chest tube placement alone was 21 +/- 3 min. Children required chest tube drainage for an average of 12.3 days. The mean time to discharge was 16.6 days. Two patients required a total of five additional operative procedures, including two additional chest tube placements, two open decortications, and one lobectomy. CONCLUSIONS: Thoracoscopic decortication is effective in the early treatment of pediatric parapneumonic empyema. It facilitates visualization, evacuation, and mechanical decortication of the pleural space with no additional morbidity and may lead to reduced time for chest tube drainage, shorter hospitalization, and more rapid clinical recovery.     

Sialuria: a second case

A case of sialuria is described in a girl who presented in the neonatal period with hepatosplenomegaly, and who has moderate developmental delay at the age of 2 years. There was massive urinary excretion of free sialic acid (N-acetylneuraminic acid). The clinical, biochemical and ultramicroscopical features were distinct from those described in Salla disease and in infantile sialic acid storage disorder.     

Preconception use of pegvisomant alone or as combination therapy for acromegaly: a case series and review of the literature

Pituitary - Pegvisomant (PEG) is an effective therapy for acromegaly. Its safety in women seeking fertility and during pregnancy has been scarcely reported. A retrospective chart review was...     

Psoriasis induced by tumor necrosis factor-alpha antagonist therapy: a case series

OBJECTIVE: Although tumor necrosis factor-alpha (TNF-alpha) antagonists are effective in the treatment of refractory psoriasis, some cases have suggested that psoriasis might be induced as a result of treatment prescribed mainly for rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. To investigate anti-TNF-alpha induced psoriasis, we conducted a systematic analysis of the 6 cases we observed among our inflammatory patient cohort treated with anti-TNF-alpha (infliximab or etanercept). METHODS: We report 6 cases of psoriasis with onset during TNF-alpha antagonist therapy (infliximab and etanercept); characteristics and skin lesions are described. RESULTS: No patient had a personal or family history of psoriasis. The development of psoriasis was seen in all the types of inflammatory diseases we treated with TNF-alpha antagonists. There was great variation in the age of affected patients and in the onset of psoriasis after initiation of TNF-alpha antagonists. Both TNF-alpha antagonists studied were associated with development of psoriasis. In 2 cases psoriasis was associated with 2 different TNF-alpha antagonists in the same patient. In half our patients, skin lesions started in the inguinal and pubic regions, but palmoplantar pustulosis was also common. In half the cases, skin lesions responded favorably with topical agents despite continuation of TNF-alpha antagonist therapy. CONCLUSION: In light of previously published cases describing psoriasis or psoriasiform lesions after TNF-alpha antagonist therapy, our series strongly confirms that TNF-alpha antagonists may induce psoriasis in some patients. Further studies are needed to identify risk factors for TNF-alpha antagonist induced psoriasis.