Coblockade of the LFA1:ICAM and CD28/CTLA4:B7 pathways is a highly effective means of preventing acute lethal graft-versus-host disease induced by fully major histocompatibility complex-disparate donor grafts

We have developed an in vitro system in which C57BL/6 donor splenocytes are exposed to B10.BR host alloantigens in the context of deficient CD28:B7 signaling as a means of preventing graft-versus-host disease (GVHD). Although 54% to 82% of MLR alloresponse was inhibited by cytotoxic T-lymphocyte antigen 4 (CTLA4)-Ig treatment of host stimulator cells, treated splenocytes were still capable of causing GVHD when infused in vivo. By adding anti-leukocyte function antigen 1 (anti-LFA1) antibody to hCTLA4-Ig in vitro to coblock the LFA1:intercellular adhesion molecule (ICAM) signaling, splenic alloresponse was inhibited by > or = 89%, yet GVHD induction capabilities were retained. Because antigen-primed cells might be more susceptible to CD28:B7 blockade, we investigated whether hCTLA4-Ig alone, anti-LFA1 antibody alone, or the combination of both added to donor-antihost in vitro primed cells could reduce GVHD. To facilitate hyporesponsiveness induction and to block B7 and ICAM ligands that are upregulated during GVHD, these reagents were also administered to recipients post-BMT. We have shown that hCTLA4-Ig plus anti-LFA1 antibody is highly effective in preventing GVHD-induced lethality (88% to 100% of treated mice surviving versus 0% to 28% of controls surviving). For optimal prevention, both hCTLA4-Ig and anti-LFA1 must be used in vitro in the context of donor-antihost primed splenocytes and continued in vivo. This in vitro-in vivo combined approach was associated with donor engraftment, and recipients were not globally immunosuppressed. We conclude that blocking both the CD28/B7 and the LFA1:ICAM pathways are critical to effective GVHD prevention and may offer advantages to in vitro donor T-cell removal.     

Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities

To determine whether untreated mild coagulopathy in patients with no evidence of clinical bleeding is associated with an increased risk of hemorrhage after paracentesis or thoracentesis, retrospective examination was conducted of 608 consecutive procedures for which prothrombin time (PT), partial thromboplastin time (PTT), platelet (Plt) counts, and preprocedure and postprocedure hemoglobin concentrations were available. There was no increased bleeding in patients with mild to moderate coagulopathy (defined as PT or PTT up to twice the midpoint normal range or pit count of 50 to 99 x 10(3) per microL [50-99 x 10(9)/L]). However, patients with markedly elevated serum creatinine levels (6.0 to 14.0 mg/dL [530-1240 mumol/L]) had a significantly greater average hemoglobin loss (-0.82 +/- 1.3 g/dL [-8 +/- 13 g/L], n = 11) than patients with normal serum creatinine levels (-0.12 +/- 0.88 g/dL [-1 +/- 9 g/L], n = 450) (p = 0.011). Overall, the frequency of bleeding complications requiring red cell transfusions was very low: 0.2 percent of events. The most common diagnosis for patients who had paracentesis was alcoholic liver disease (72%); for those having thoracentesis, it was infection (37%). It can be concluded that, for these patients, prophylactic plasma or platelet transfusions are not necessary. Patients with markedly elevated serum creatinine deserve close postprocedure observation.     

Storage of platelet concentrates after high-dose ultraviolet B irradiation

Ultraviolet B (UVB) irradiation of platelet concentrates (PCs) may prevent the development of posttransfusion HLA alloimmunization. As irradiation performed in a blood center or a hospital will probably be associated with a variable postirradiation delay before transfusion, the ability to store PCs after UVB irradiation becomes important. The effects have been studied of a UVB dose of 10,000 mJ per cm2, the dose used in our institution for UVB clinical trials, on PCs pooled and stored for up to 96 hours after irradiation. Results showed that after 96 hours of storage, though there were no changes in pH, platelet count, white cell count, percent discharge of lactate dehydrogenase, or beta-thromboglobulin, there were significant decreases in morphology score and osmotic recovery. These changes, however, were not evident after 24 hours of storage. Similarly, there was a 60-percent decrease in immunoreactive membrane glycoprotein (GP) Ib after 96 hours of storage, but these changes were not seen after 48 hours of storage. No changes were seen in levels of GPIIb/IIIa in either group during the 96 hours of storage. On computer-analyzed two-dimensional polyacrylamide gel electrophoresis, PCs irradiated at 10,000 mJ per cm2 and stored for 72 hours had changes in over 50 platelet proteins as compared to those proteins in nonirradiated age-matched control PCs. It can be concluded that UVB irradiation of PCs at 10,000 mJ per cm2 does not lead to significant platelet deterioration after short-term storage (24-48 hours) but is likely to be deleterious after long-term (72-96 hours) storage.(ABSTRACT TRUNCATED AT 250 WORDS)     

儿童朗格汉斯组织细胞增生症侵犯肋骨的X线与CT比较

目的回顾性分析15例儿童肋骨朗格汉斯组织细胞增生症（LCH）的X线和CT表现,以提高对该病认识。方法收集2012年1月—2013年6月经病理证实的儿童肋骨LCH患儿15例;所有患儿均行X线胸部正位片和胸部CT平扫检查,其中4例加行CT增强扫描。患儿发病年龄1个月-12岁,中位年龄3岁;男性9例、女性6例。分析所有患儿临床资料和影像学表现。结果 15例患儿中,8例临床表现为局部肿块,3例伴局部疼痛,其余病变无明显症状。7例表现为肋骨单发病灶,其中3例仅表现为肋骨病变、4例伴其他系统病变。8例为多发病灶,均伴发其他系统病变。15例共25个病灶中,胸片只发现19个;有2例共6个病灶胸片未发现明显病变。X线胸部正位片病灶检出率为76%。病灶在X线胸部平片上表现为边界清楚的骨质破坏。CT均表现为类圆形或多囊性膨胀性溶骨性骨质破坏;12个病灶（48%）可见硬化;3个（12%）伴软组织肿块,软组织肿块与骨病变伴行,增强后软组织肿块表现为明显强化。结论儿童肋骨LCH的X线胸部正位片检出率相对较低,需行CT对病变范围及周围组织器官侵犯情况进一步评价。发生在儿童肋骨的类圆形或多囊性、边界清楚的溶骨性骨质破坏,伴或不伴明显强化的软组织肿块,常提示LCH的诊断。     

Early‐onset,progressive, frequent,extensive, and severe bone mineral and renal complications in multiple endocrine neoplasia type 1–associated primary hyperparathyroidism

Differences in bone mineral density (BMD) patterns have been recently reported between multiple endocrine neoplasia type 1–related primary hyperparathyroidism (HPT/MEN1) and sporadic primary HPT. However, studies on the early and later outcomes of bone/renal complications in HPT/MEN1 are lacking. In this cross‐sectional study, performed in a tertiary academic hospital, 36 patients cases with uncontrolled HPT from 8 unrelated MEN1 families underwent dual‐energy X‐ray absorptiometry (DXA) scanning of the proximal one‐third of the distal radius (1/3DR), femoral neck, total hip, and lumbar spine (LS). The mean age of the patients was 38.9 ± 14.5 years. Parathyroid hormone (PTH)/calcium values were mildly elevated despite an overall high percentage of bone demineralization (77.8%). In the younger group (<50 years of age), demineralization in the 1/3DR was more frequent, more severe, and occurred earlier (40%; Z‐score ?1.81 ± 0.26). The older group (>50 years of age) had a higher frequency of bone demineralization at all sites (p < .005) and a larger number of affected bone sites (p < .0001), and BMD was more severely compromised in the 1/3DR (p = .007) and LS (p = .002). BMD values were lower in symptomatic (88.9%) than in asymptomatic HPT patients (p < .006). Patients with long‐standing HPT (>10 years) and gastrinoma/HPT presented significantly lower 1/3DR BMD values. Urolithiasis occurred earlier (<30 years) and more frequently (75%) and was associated with related renal comorbidities (50%) and renal insufficiency in the older group (33%). Bone mineral– and urolithiasis‐related renal complications in HPT/MEN1 are early‐onset, frequent, extensive, severe, and progressive. These data should be considered in the individualized clinical/surgical management of patients with MEN1‐associated HPT. © 2010 American Society for Bone and Mineral Research.     

Pilot Study on Documentation Skills: Is There Adequate Training in Emergency Medicine Residency?

Background: Thorough and accurate documentation in the medical record is important, and documentation skills should be an integral component of emergency medicine (EM) residency training. Study Objective: We sought to study the documentation skills of EM residents as they relate to emergency department (ED) reimbursement. Methods: This was a retrospective, cross-sectional study. We reviewed all charts of patients presenting to the adult ED during a 2-week period. We compared three groups: patients seen primarily by an EM resident, patients seen primarily by a physician assistant (PA), and patients seen primarily by an attending emergency physician. Outcome measures were the incidence of downcodes and dollars lost to downcodes in all groups. Results: There were 212 patients in the resident group, 683 patients in the PA group, and 437 patients in the attending group. There were 12 downcodes (5.7%, 95% confidence interval [CI] 2.96–9.70) in the resident group, 10 downcodes (1.5%, 95% CI 0.70–2.68) in the PA group, and 17 downcodes (3.9%, 95% CI 2.28–6.14) in the attending group (p = 0.002). The mean dollar lost per patient seen in the resident group was $3.21 (95% CI 1.41–5.00); $0.91 (95% CI 0.33–1.49) in the PA group; and $2.23 (95% CI 1.17–3.28) in the attending group (p = 0.002). Conclusion: Charts documented primarily by EM residents were more likely to be downcoded than charts documented primarily by PAs or ED attendings. This downcode rate resulted in a greater loss of revenue in the resident group. We believe this represents an area for improvement in EM residency education.