Immunosuppression in renal transplantation: Long-term clinical trial of a double versus triple therapy regimen

Summary: Sixty-nine renal allograft recipients were randomized to two immunosuppressive regimens: 35 patients received cyclosporine A and prednisolone (PC) while 34 patients received low dose cyclosporine A, prednisolone and short term azathioprine (PCA). the data of 66 patients (34 in PC and 32 in PCA groups) were analysed. the median follow-up periods were 62 months for the PC group and 60 months for the PCA group. There was no difference in graft survival between the two groups but five patients died in the PC group compared to none in the PCA group (graft survival: 88 vs 90% at 1 year and 82 vs 82% at 5 years, P = not significant at any time point; patient survival: 90 vs 100% at 1 year and 88 vs 100% at 5 years, P = 0.05 at 5 years). There was a trend for patients in the PCA group to develop earlier and more frequent rejections (not significant; P = 0.106 and P = 0.062, respectively). There were also more episodes of acute cyclosporine A nephrotoxicity and cytomegalovirus (CMV) infection in the PC group. the mean serum creatinine at 5 years was significantly higher in the PCA group when compared to the PC group (179.8 ± 76.5 μmol/L vs 154.7 ± 41.0 μmol/L; P =0.05). We found that both therapeutic regimens were effective in preventing renal allograft rejections. However, double therapy was associated with higher patient mortality secondary to infection. Patients on triple therapy, on the other hand, were more prone to develop rejections in the early post-transplant period and were associated with less favourable renal function in the long run.     

Alimentation calcique et effet de l'entraînement physique sur l'os

Physical exercise is able to influence bone structure. In the principal part of cases, physical training results in an enhanced bone density when in any case overtraining could decrease bone density. Numerous factors are involved in the effect of physical training on bone, dietary calcium supply being one. Numerous epidemiological surveys have shown that the daily calcium supply in the French population is between 500 and 1,200 mg/24 hours. Thus part of the French population is under the recommended intake of 1,000 mg. It was proposed that physical training could improve calorie intake and consequently calcium supply. The main objective of this paper is the relationship between exercise and bone structure: second, literature is used to present the role of dietary calcium on bone structure. Finally, the data of a survey in a French population are used in order to define to what extent calcium dietary supply of different sports groups agree with the dietary recommended allowance. They report that calcium supply is influenced by the type of sport, strength trained atheletes enhance calcium intake while endurance trained atheletes present lower calcium intake.     

中国羊踯躅花化学成分研究

从国产杜鹃花科植物羊踯躅(Rhododendron molle G.Don)的花中分离得到两种有药理活性的成分。经光谱(IR,MS,¹HNMR,¹³CNMR,¹H-¹H COSY,¹H-¹H NOESY,¹³C-¹H COSY)等分析证明其中一种为新的四环二萜类化合物。命名为羊踯躅素Ⅲ(rhodomollein Ⅲ)(1)。     

顺-3-甲基芬太尼的4-N-丙酰基结构类似物的合成与镇痛活性及构效关系的研究

以不同电性的基团取代顺-3-甲基芬太尼中4-N-丙酰基上的乙基,合成某些顺-3-甲基芬太尼的结构类似物。药理试验结果表明,所合成的化合物均有典型的吗啡样作用。化合物3的镇痛活性略强于顺-3-甲基芬太尼。应用半经验的INDO方法对4个代表化合物进行了量子化学计算,讨论了电子结构与镇痛活性间的关系,化合物3由于氯乙烯基的引入具有与顺-3-甲基芬太尼不同的电子结构特征,氯乙烯基可能作为电子接受体参与了与受体的作用。     

Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate

High-dose chemotherapy and autologous stem cell transplantation are used increasingly to treat patients with light-chain-related amyloidosis (AL). Treatment-related mortality is approximately 15%. To enable more patients to undergo stem cell transplantation, a risk-adapted strategy has been developed to treat with lower chemotherapy doses those patients who are at excessive risk. It is unclear whether reducing the chemotherapy dose in patients at excessive risk of treatment toxicity reduces the overall response. We retrospectively reviewed 171 AL patients who underwent conditioning chemotherapy with stem cell transplantation. The patients comprised two groups: those receiving standard high-dose melphalan and those receiving intermediate-dose melphalan. Responses were categorized as hematologic response, which used criteria for myeloma response. The two groups showed statistically significant differences; the overall response rates were 75% in the high-dose group and 53% in the intermediate-dose group although treatment-related mortality was the same in both groups. Reducing the melphalan dose appeared to render more AL patients eligible for stem cell transplantation but sacrificed an element of response. Methods are needed to reduce treatment-related toxicity so that more patients can receive full-dose conditioning chemotherapy.     

Surgical Approach and Oncologic Outcomes Following Multidisciplinary Management of Retrorectal Sarcomas

Background

Retrorectal sarcomas are rare, and limited data are available on oncologic outcomes following surgery. Our aim was to evaluate outcomes in this patient population at our institution.

Materials and Methods

All patients who underwent surgical resection of a malignant retrorectal/presacral sarcoma between 1985 and 2005 were identified. Data analyzed included demographics, histopathologic diagnosis, surgical morbidity and mortality, use of adjuvant therapy, local and distant recurrence, and survival.

Results

A total of 37 patients were identified (20 males) with a median age of 49 years (range, 22–81 years). The most common histopathologic diagnosis was malignant peripheral nerve sheath tumor (n = 8). Also, 22 tumors were high grade and 15 were low grade. Surgical margin status was R0 in 31 patients and R1 in 6. Adjuvant therapy was given to 26 patients. Postoperative morbidity and mortality was 57% and 3%, respectively. Median length of follow-up in 16 patients alive at last contact was 4.7 years. The 5-year survival free of local (LDFS), distant (DDFS), and local or distant recurrence (DFS) was 51, 58, and 39%, respectively. Patient survival at 2, 5, and 10 years was 75, 55, and 47%, respectively. Disease-free survival was not significantly associated with gender (P = .16), primary vs secondary (P = .94), R0 vs R1 resection (P = .26), low vs high tumor grade (P = .17), or the use of surgery with or without adjuvant therapy (P = .33).

Conclusions

Retrorectal sarcomas are often high grade and locally advanced. Most tumors are resectable with free margins, and long-term survival may be possible in up to one-half of patients following an aggressive surgical approach.     

Primary schwannoma of the bone: a clinicopathologic and radiologic study of 17 cases

Primary schwannoma of the bone, defined as arising within the medullary cavity and radiologically mimicking more common primary bone tumors, is rare. We present 17 tumors, 13 conventional schwannomas, and 4 melanotic type. Collectively, they represented <1% of all primary bone tumors seen at Mayo Clinic over a 33-year period. Most tumors affected long bones. There was a slight female predilection. Fifteen tumors were sporadic, and 2 were syndrome associated (Carney complex). Pain was the most common symptom. Given their rarity, schwannomas of the bone are not usually included in the differential diagnosis of primary osseous spindle cell tumors. Thus, they are prone to misdiagnosis and overtreatment. Similar to their more common extraosseous counterparts, primary schwannomas of the bone behave in a benign manner and are successfully treated by local excision alone.     

The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin''s lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.     

Role of systemic high-dose methotrexate and combined approaches in the management of vitreoretinal lymphoma: A single center experience 1990-2018

Vitreoretinal lymphoma (VRL) management remains a challenge. We present 72 patients with VRL, diagnosed at Mayo Clinic between 1990-2018. Three nondiffuse large B-cell lymphoma (DLBCL) histology cases were excluded. Among 69 DLBCL, 33 patients had primary VRL (PVRL), 18 concurrent intraocular and central nervous system (CNS) or systemic disease and 18 secondary VRL. Patients received intraocular chemotherapy (intraocular injections of rituximab or metothrexate or steroids or in combination), radiotherapy, systemic or combined systemic plus intraocular treatment in 9, 10, 35, and 15 cases, respectively. Among primary and concurrent VRL, median failure free survival (FFS), CNS relapse-free survival (CNS-RFS) and overall survival (OS) were: 1.8, 4.9, and 4.1 years, respectively; among PVRL, median FFS, CNS-RFS, and OS were: 2.6 year, Not Reached and 9.3 year, respectively. No CNS relapse occurred beyond 4 years in PVRL. Median OS for patients diagnosed between 1990 and 1999 vs between 2000 and 2018 was 1.5 vs 9.4 years, respectively (P = .0002). OS was significantly higher in PVRL, as compared with concurrent VRL (P = .04). Previous immunosuppression and poor performance status were predictive of worse outcome. In PVRL, a combined systemic and intraocular therapy showed higher FFS (P = .002) and CNS-RFS (P = .003), but no differences in OS. Among 18 secondary VRL, at a median follow-up of 1.1 year after vitreoretinal relapse, median FFS and OS were 0.3 and 1.3 years. An improvement in survival of VRL has been observed over the decades. PVRL should undergo combined systemic and intraocular chemotherapy to prevent CNS progression.