Diffuse alveolar damage in patients with dermatomyositis: a six-case series

The clinical course of diffuse alveolar damage (DAD) was studied in six consecutive cases of dermatomyositis (DM) based on our hospital records over 8 years. Three patients had severe myopathy at presentation, and the other three patients showed clinically amyopathic DM (CADM). Interstitial pneumonia in all patients developed shortly after they manifested DM. DAD in five deceased patients, which was proven pathologically, did not respond to steroid therapy combined with cyclosporine or tacrolimus. Of these, two patients began receiving combination therapy before suffering respiratory symptoms, and one of them had elevated serum Krebs von der Lungen-6 (KL-6) levels before visible abnormalities appeared on a plain chest X-ray. Only one patient with CADM survived; this patient received intravenously administered pulse cyclophosphamide (IVCY) therapy intravenously for DAD from the early stage. Delayed adjunctive IVCY was ineffective for progressed DAD in the remaining five patients. Elevated serum ferritin levels were observed in all four patients examined and might have predicted the lethal DAD, as in a previous report. In conclusion, promptly beginning IVCY therapy may be beneficial for patients with DM and interstitial pneumonia who show elevated serum levels of ferritin or KL-6 with minimal pulmonary abnormalities.     

Success rate of terbutaline in inhibiting preterm labor for 48 h

Objective: To determine terbutaline success rate in postponing preterm labor for 48?h and to identify factors associated with its efficacy, side effects, maternal and neonatal outcomes.

Methods: A retrospective study analyzing data from pregnant women suffering from preterm labor who had received terbutaline for inhibition of labor from January 2007 to December 2013.

Results: A total of 385 cases were analyzed; there were 321 cases (83.4%) delivered ≥48?h and 64 cases (16.6%) delivered before 48?h. The factors that affect the success rate of terbutaline administration in singleton pregnancy were cervical dilatation (ORs 0.37; 95% CI 0.18–0.79) and cervical effacement (ORs 0.36; 95% CI 0.17–0.75). The most common side effect of terbutaline was tachycardia (95.1%), but there were no serious cardiovascular events and maternal death. Mean neonatal birth weight was 2.294.3?±?638.4?g. Neonatal complications included respiratory distress syndrome (RDS) 16.2%, intraventricular hemorrhage (IVH) 1.4%, necrotizing enterocolitis (NEC) 0.7%, sepsis 5.3%, and neonatal death 0.9%.

Conclusions: The success rate of terbutaline in treatment of preterm labor was high whereas side effects were tolerable. Neonatal outcome was good. The factors that significantly affect the success rate of terbutaline administration in singleton pregnancy were cervical dilatation and cervical effacement. Thus, terbutaline can be used safely for short-term treatment of preterm labor.     

Impact of biomarker changes during neoadjuvant chemotherapy for clinical response in patients with residual breast cancers

Background

Residual cancer burden or Ki67 expression levels in residual tumors reportedly provided significant prognostic information for a non-pathological complete response subset after neoadjuvant chemotherapy (NAC). However, the significance of Ki67 reduction for clinical response during chemotherapy in each subtype or menopausal status is yet to be determined.

Methods

A total of 183 breast cancers surgically removed after chemotherapy were recruited for this study. Expression levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki67 were determined immunohistochemically for semiquantitative measurement and these biomarkers were compared in pre- and post-NAC samples from pathological non-responders (n = 125). Responses to chemotherapy were evaluated both clinically and pathologically.

Results

Ki67 expression levels after NAC (median 5 %, range 0–70 %) were significantly reduced compared with before NAC (25, 1–80 %, P < 0.0001), but only in patients who attained clinical response. This significant suppression of Ki67 in clinical responders was consistently observed in breast cancers from the ER-positive subset, but not the ER-negative subset in the total test set (n = 120). These observations were also made in the validation set (n = 63). Among premenopausal, but not postmenopausal patients, a significant decrease in PgR expression levels was detected in breast cancers of patients who attained clinical response (pre-NAC 50, 0–100 %, post-NAC 5, 0–20 %; P = 0.0003).

Conclusion

The impact of Ki67 suppression on clinical response seems to be restricted to ER-positive breast cancers. Since PgR expression levels of premenopausal ER-positive cancers were significantly reduced in clinical responders, inhibition of estrogen signaling due to chemotherapy-induced amenorrhea may be involved in this association.

     

Palliative care needs of cancer outpatients receiving chemotherapy: an audit of a clinical screening project

Purpose Although more and more cancer patients are receiving chemotherapy in outpatient settings in their advanced stage and could have a broad range of palliative care needs, referral to the specialized palliative care service is often delayed. The primary aim of this study is to explore the usefulness of a combined intervention for cancer patients in identifying patients with underrecognized palliative care needs and referring them to the specialized palliative care service. The intervention consisted of (1) introducing the specialized palliative care service when starting chemotherapy, (2) using screening tools, and (3) providing on-demand specialized palliative care service. Materials and methods All cancer patients newly starting chemotherapy with primary tumor sites of the lung, gastrointestine, pancreas, bile duct, breast, ovary, and uterus were included. As routine practice, at the first instruction about chemotherapy, pharmacists provided information about the role of the specialized palliative care service using a pamphlet and handed out screening questionnaires. Screening questionnaires were distributed at every hospital visit. Treating physicians and/or nurses checked the questionnaire before examining the patients. The patients were referred to the palliative care team, if (1) the patients voluntarily wished for the specialized palliative care service or (2) the treating physicians clinically determined that, on the basis of the screening results, the patients had physical or psychological needs appropriate for referral to the specialized palliative care service. The screening questionnaire included an open-ended question about their greatest concerns, the severity of 11 physical symptoms, overall quality-of-life, the distress thermometer, help for information about the treatment and decision-making, economic problems, nutrition, daily activities, and wish for help from the specialized palliative care service. Results Of 211 patients who newly started chemotherapy, 5 patients refused to complete the questionnaire (compliance rate, 98%). We obtained 1,000 questionnaires from 206 patients. The percentages of missing values ranged from 2.7% to 7.0%. Of 206 patients, 38 (18%) were referred to the palliative care team due to newly recognized problems, in addition to 10 patients with problems well-recognized by primary physicians. The total percentage of patients receiving specialized palliative care service was thus 23% of all patients. Frequently identified problems were oral problems (20%), insomnia (20%), help with information and decision-making (16%), psychological distress defined as the distress thermometer (14%), severe fatigue (9.0%), and severe appetite loss (8.8%). As a whole, problems were identified in half of all questionnaires. Conclusion The combined intervention of introducing the specialized palliative care service, using screening tools and providing on-demand specialized palliative care service, was feasible as part of the routine clinical practice for all cancer patients starting chemotherapy. It might be useful in identifying patients with underrecognized palliative care needs and referring them to the specialized palliative care service at the appropriate time.     

The anti-influenza drug oseltamivir evokes hypothermia in mice through dopamine D2 receptor activation via central actions

Oseltamivir has a hypothermic effect in mice when injected intraperitoneally (i.p.) and intracerebroventricularly (i.c.v.). Here we show that the hypothermia evoked by i.c.v.-oseltamivir is inhibited by non-selective dopamine receptor antagonists (sulpiride and haloperidol) and the D₂-selective antagonist L-741,626, but not by D₁/D₅-selective and D₃-selective antagonists (SCH-23390 and SB-277011-A, respectively). The hypothermic effect of i.p.-administered oseltamivir was not inhibited by sulpiride, haloperidol, L-741,626 and SCH-23390. In addition, neither sulpiride, haloperidol nor SCH-23390 blocked hypothermia evoked by i.c.v.-administered oseltamivir carboxylate (a hydrolyzed metabolite of oseltamivir). These results suggest that oseltamivir in the brain induces hypothermia through activation of dopamine D₂ receptors.     

Collagen of chronically inflamed skin is over-modified and upregulates secretion of matrix metalloproteinase 2 and matrix-degrading enzymes by endothelial cells and fibroblasts

In order to investigate the properties of collagen in chronically inflamed tissue, we isolated collagen from the ear skin of mice with chronic contact dermatitis and examined its biochemical characteristics and the functions that regulate the secretion of matrix metalloproteinase 2 and collagen-degrading enzymes from endothelial cells and fibroblasts. Collagen in skin with chronic contact dermatitis comprised 60% type I collagen and 40% type III collagen, which latter is higher than the content of type III collagen in control skin (35%). The denaturation temperature was higher (42 degrees C) than that of control skin (39 degrees C). The alpha2 chain of type I collagen was over-hydroxylated at both proline and lysine residues. Segment-long-spacing crystallites of type I collagen were unusually connected in tandem. Collagen of chronically inflamed skin was less susceptible to matrix metalloproteinase 2 after heat denaturation. Endothelial cells and fibroblasts secreted an increased amount of matrix metalloproteinase 2 when cultured on a gel formed from the collagen of chronically inflamed skin. Collagen-degrading activity secreted from fibroblasts was also upregulated when cells were in contact with collagen of chronically inflamed skin. These results suggest that the collagen in chronically inflamed tissue has altered biochemical characteristics and functions, which may affect the pathogenesis of the chronic skin disease.