A fatal case of bortezomib‐induced lung toxicity in a young adult heart transplant recipient

Bortezomib is approved for the treatment of multiple myeloma but increasingly used in heart transplant (HTx) recipients with antibody‐mediated rejection (AMR). Severe pulmonary toxicity is a rare complication in multiple myeloma patients treated with bortezomib, but has not been described in a solid organ transplant recipient. A 20‐year‐old man 7 years post‐HTx presented with acute rejection with hemodynamic compromise. Endomyocardial biopsy showed mixed rejection (ISHLT grade 2R‐3R acute cellular rejection (ACR) and pAMR 1 (I+) with diffuse C4d staining). Two new high MFI circulating MHC class‐II donor‐specific antibodies (DSA) were detected. Treatment included corticosteroids, antithymocyte globulin, plasmapheresis, IVIG, rituximab, and bortezomib (1.3 mg/m²). Due to rebound in DSA, a second course of bortezomib was started. Thrombocytopenia and peripheral neuropathy prompted a 50% dose reduction during the 2nd course. Shortly after the 3rd reduced dose, the patient developed hypoxemic respiratory failure. Bronchoscopy revealed pulmonary hemorrhage with negative infectious studies. Chest CT showed bilateral parenchymal disease with bronchiectasis and alveolar bleeding. Despite treatment with high‐dose steroids, severe ARDS ensued with multisystem organ failure. The patient expired 23 days after the final dose of bortezomib. Post‐mortem lung histology revealed diffuse alveolar damage, pulmonary fibrosis, and hemorrhage. Cardiac histology showed resolving/residual ACR 1R and pAMR 1 (I+). While rare, bortezomib‐induced lung toxicity (BILT) can occur in HTx recipients and can carry a high risk of mortality. Drug reaction and immediate drug withdrawal should be considered in patients who develop respiratory symptoms, though optimal management of BILT is unclear.     

Homozygosity for a partial deletion of apoprotein A-V signal peptide results in intracellular missorting of the protein and chylomicronemia in a breast-fed infant

Deficiency of apoprotein A-V (apoA-V) can cause hypertriglyceridemia. In an 11 months old boy presenting with a severe hypertriglyceridemia, a formerly unknown 24 nucleotide deletion in exon 2 of the APOA5 gene was detected. The homozygous mutation results in an eight amino acid loss in the signal peptide sequence (c.16_39del; p.Ala6_Ala13del). Screening of control persons proved that this deletion is a rare mutation. Hypertriglyceridemia in the patient was only found at the time when he was breast fed, while after weaning, triglyceride levels were close to normal. Under both dietary conditions, apoA-V protein was undetectable in plasma while post-heparin plasma lipoprotein lipase activity was normal.     

Diffusion-weighted MR imaging in acute ischemia: value of apparent diffusion coefficient and signal intensity thresholds in predicting tissue at risk and final infarct size

BACKGROUND AND PURPOSE: Identifying tissue at risk for infarction is an important goal of stroke imaging. This study was performed to determine whether pixel-based apparent diffusion coefficient (ADC) and signal intensity ratio are helpful diffusion-weighted (DW) imaging metrics to predict tissue at risk for infarction. METHODS: Twelve patients presenting with acute hemispheric strokes underwent DW imaging within 7 hours of symptom onset. Region of interest (ROI), pixel-based ADC, and signal intensity analyses were performed at initial DW imaging to assess area of infarct growth, final infarct area, and normal tissue. RESULTS: Pixel-based analysis was less accurate than ROI-based analysis for evaluating infarct growth or final infarct with ADC, ADC ratio, and signal intensity ratios. In pixel-based analysis, signal intensity ratios were better than ADCs or ADC ratios for identifying tissue at risk (accuracy, 67.4%) and for predicting final infarct (accuracy, 79.9%). Linear regression analysis demonstrated a strong correlation between lesion volume on quantitative DW images or ADC maps and final infarct volume (P < .001). When receiver operating characteristic (ROC) curves were used to determine optimal cutoffs for ADC and DW image values, the region of infarct growth was significantly correlated with only the mismatch between initial qualitative DW image and quantitative DW image signal intensity ratio (cutoff value, 1.19; R = 0.652; P = .022). CONCLUSION: Pixel-based thresholds applied to ADC or DW image signal intensity maps were not accurate prognostic measures of tissue at risk. Quantitative DW images or ADC maps may provide added information not obtained by visual inspection of the qualitative DW image map.     

MR-sequences for prostate cancer diagnostics: validation based on the PI-RADS scoring system and targeted MR-guided in-bore biopsy

Purpose

This study evaluated the accuracy of MR sequences [T2-, diffusion-weighted, and dynamic contrast-enhanced (T2WI, DWI, and DCE) imaging] at 3T, based on the European Society of Urogenital Radiology (ESUR) scoring system [Prostate Imaging Reporting and Data System (PI-RADS)] using MR-guided in-bore prostate biopsies as reference standard.

Methods

In 235 consecutive patients [aged 65.7?±?7.9 years; median prostate-specific antigen (PSA) 8 ng/ml] with multiparametric prostate MRI (mp-MRI), 566 lesions were scored according to PI-RADS. Histology of all lesions was obtained by targeted MR-guided in-bore biopsy.

Results

In 200 lesions, biopsy revealed prostate cancer (PCa). The area under the curve (AUC) for cancer detection was 0.70 (T2WI), 0.80 (DWI), and 0.74 (DCE). A combination of T2WI + DWI, T2WI + DCE, and DWI + DCE achieved an AUC of 0.81, 0.78, and 0.79. A summed PI-RADS score of T2WI + DWI + DCE achieved an AUC of 0.81. For higher grade PCa (primary Gleason pattern?≥?4), the AUC was 0.85 for T2WI + DWI, 0.84 for T2WI + DCE, 0.86 for DWI + DCE, and 0.87 for T2WI + DWI + DCE. The AUC for T2WI + DWI + DCE for transitional-zone PCa was 0.73, and for the peripheral zone 0.88. Regarding higher-grade PCa, AUC for transitional-zone PCa was 0.88, and for peripheral zone 0.96.

Conclusion

The combination of T2WI + DWI + DCE achieved the highest test accuracy, especially in patients with higher-grade PCa. The use of ≤2 MR sequences led to lower AUC in higher-grade and peripheral-zone cancers.

Key Points

? T2WI + DWI + DCE achieved the highest accuracy in patients with higher grade PCa ? T2WI + DWI + DCE was more accurate for peripheral- than for transitional-zone PCa ? DCE increased PCa detection accuracy in the peripheral zone ? DWI was the leading sequence in the transitional zone     

Does Epidural Analgesia Affect the Rate of Spontaneous Obstetric Lacerations in Normal Births?

The precise relationship between epidural use and genital tract lacerations in normal childbirth is unclear. Data from a clinical trial on measures to lower genital tract trauma in vaginal birth were used for a secondary analysis. The goal was to assess whether epidurals affect the rate of spontaneous obstetric lacerations in normal vaginal births. Maternal characteristics and intrapartum variables were compared in women who did and did not use an epidural in labor, and also in those with and without any sutured lacerations following vaginal birth. Variables that were statistically different in both cases were entered into regression equations for simultaneous adjustment. Epidural use was not an independent predictor of sutured lacerations. Predictors of sutured lacerations included nulliparity, a prolonged second stage, being non-Hispanic white, and an infant birthweight greater than 4000 grams. Elements of midwifery management need further research.     

Minimizing genital tract trauma and related pain following spontaneous vaginal birth

Genital tract trauma is common following vaginal childbirth, and perineal pain is a frequent symptom reported by new mothers. The following techniques and care measures are associated with lower rates of obstetric lacerations and related pain following spontaneous vaginal birth: antenatal perineal massage for nulliparous women, upright or lateral positions for birth, avoidance of Valsalva pushing, delayed pushing with epidural analgesia, avoidance of episiotomy, controlled delivery of the baby's head, use of Dexon (U.S. Surgical; Norwalk, CT) or Vicryl (Ethicon, Inc., Somerville, NJ) suture material, the "Fleming method" for suturing lacerations, and oral or rectal ibuprofen for perineal pain relief after delivery. Further research is warranted to determine the role of prenatal pelvic floor (Kegel) exercises, general exercise, and body mass index in reducing obstetric trauma, and also the role of pelvic floor and general exercise in pelvic floor recovery after childbirth.     

The evidence for physiologic management of the active phase of the first stage of labor

The active phase of first stage labor is generally defined as the period between 3 cm to 4 cm to complete cervical dilatation, in the presence of regular uterine contractions. Most women will experience this portion of labor within hospital obstetric units, where care commonly features restriction to bed, electronic fetal monitoring, early treatment of "slow" labors, and few pain management options beyond epidurals and narcotics. However, the available evidence on appropriate care for healthy childbearing women favors activity in labor, intermittent auscultation, patience from caregivers, and nonpharmacologic methods of pain relief. This article reviews the evidence for care practices that support physiologic labor. Modifying intrapartum care to reflect current evidence will improve women's health, and will require a multilevel approach and consistent midwifery demonstration of the model.     

甲地孕酮联合化疗对晚期非小细胞肺癌生活质量的影响

目的:比较甲地孕酮联合NP方案和单用NP方案化疗对晚期非小细胞肺癌生活质量的影响,评价甲地孕酮的临床疗效。方法:将60例晚期非小细胞肺癌患者随机分为治疗组与对照组。治疗组30例,于化疗前2天口服甲地孕酮160 mg,2次/d,同时予NP方案化疗。对照组30例仅接受NP方案化疗。于化疗4周期后评价患者的食欲、体重变化、KPS评分及不良反应。结果:经过4个周期后治疗组食欲、体重、KPS评分改善情况与对照组相比差异有统计学意义(P<0.05)。治疗组主要不良反应为高血压、便秘、血糖升高、皮疹、阴道流血、踝部水肿等反应,经对症处理后可缓解。结论:甲地孕酮可改善晚期非小细胞肺癌患者的生活质量,减轻其不良反应,不良反应可耐受。     

急性白血病完全缓解后患乳腺癌1例

1 病例报告女,51岁. 因发热、关节疼痛、齿龈胀痛、左下肺感染20 d,抗生素治疗无效,于2001-11-29入我院血液科治疗. 查体:T 37.5℃,P 120次/min,R 18次/min,BP 110/50 kPa,贫血外观,巩膜无黄染,皮肤黏膜无出血,右颌下可触及一黄豆粒大小淋巴结,触痛(±),胸骨压痛( ),心率120次/min,律齐,无病理性杂音. 双肺未闻及干湿啰音. 腹软,肝脾未触及,四肢运动正常. 既往史:曾于1992年行"乳腺小叶切除术",1999年因子宫肌瘤行"子宫次全切除术". 家族史:其姐姐1982年患乳腺癌,因肺转移已于1983年病故.