Two Extremely Preterm Infants Discharged with a Home High-Flow Nasal Cannula for Severe Bronchopulmonary Dysplasia.

Home high-flow nasal cannula (HFNC) use in the neonatal field has become prevalent as a noninvasive respiratory support, but its application in home care remains rare. We report two cases in which a home HFNC was effective in managing extremely low-birth-weight infants with severe bronchopulmonary dysplasia (BPD). Case 1 was a male infant born at 22 weeks' gestation weighing 435 g. Case 2 was a female infant born at 23 weeks' gestation weighing 450 g. Both patients had mothers with chronic placental abruption or chorioamnionitis. They transitioned from invasive mechanical ventilation to nasal CPAP (nCPAP) at 45 days (case 1) and 50 days (case 2) old. Subsequently, at 324 days (case 1) and 90 days (case 2) old, they transitioned to a HFNC, demonstrating stable oxygenation and ventilation, but faced difficulty in removal. Considering the drawbacks of prolonged hospitalization, the patients were discharged using a home HFNC at 404 days (case 1) and 391 days (case 2) old. For case 1, the HFNC was set at 4 L/min of room air and 2 L/min of oxygen, whereas for case 2, it was set at 5 L/min of room air and 1 L/min of oxygen. These settings maintained an SpO2 above 90% and a pCO2 below 60 mmHg. An HFNC offers advantages over nCPAP owing to its lower invasiveness and reduced discomfort for long-term use. However, reports on the use of a home HFNC for BPD are scarce. In recent years, while premature infant mortality has decreased worldwide, the incidence of BPD has risen, necessitating preparedness for prolonged ventilation in preterm infants. Home ventilators represent a strategy to prevent extended hospitalization, and based on our cases, home HFNC for BPD appears safe and effective, making it potentially useful for managing preterm infants requiring prolonged respiratory support in the future.

Population pharmacokinetics of laninamivir and its prodrug laninamivir octanoate in healthy subjects and in adult and pediatric patients with influenza virus infection.

Laninamivir octanoate (LO) is a new neuraminidase inhibitor for inhalation. The objectives of this study were to model the population pharmacokinetics of LO and its active metabolite laninamivir after inhaled administration of LO using a pooled population of healthy subjects, and adult and pediatric patients with influenza virus infection from 8 clinical studies, and to evaluate covariate effects on pharmacokinetics. The pharmacokinetics of LO and laninamivir in plasma and urine are well-described by structural models that consist of a 2-compartment model for LO with instantaneous bolus input and first-order elimination; and a 1-compartment model for laninamivir with formation of laninamivir via the metabolic pathway from LO in systemic circulation, entry of laninamivir from the respiratory tract compartment, and linear elimination. Creatinine clearance was identified as a covariate of apparent total clearance for LO and renal clearances for LO and laninamivir, with the largest effect on laninamivir exposure. Body weight was identified to affect distribution volumes of LO and laninamivir and the metabolic clearance of LO; however there was no notable effect on exposures across the wide body weight range evaluated. The population pharmacokinetic model also provides insight into the likely kinetics of drug disposition in the respiratory tract following inhaled administration.

Extended biopsy based criteria incorporating cumulative cancer length for predicting clinically insignificant prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? The criteria used for selecting patients with prostate cancer for active surveillance (AS) are still not satisfactory due to the difficulty in predicting the significance of the prostate cancer. Urologists could predict insignificant prostate cancer by incorporating cumulative cancer length and biopsy Gleason score, derived from extended biopsy. The present study has added new criteria for predicting insignificant prostate cancer, which would lead to a better selection of candidates for AS. OBJECTIVE: • To develop extended biopsy based criteria for predicting insignificant cancer (IC) using extended biopsy findings. PATIENTS AND METHODS: • From 2000 to 2009, 1575 patients with prostate cancer were primarily treated by radical prostatectomy in two referral hospitals. • Of these, the study cohort comprised 499 patients with extended biopsy confirmed, clinically organ-confined (cT1-2N0M0) prostate cancer with PSA levels of <20 ng/mL. • Cancer information obtained through extended biopsy included cumulative cancer length (CCL) divided by the number of biopsy cores (CCL/core). RESULTS: • Pathological examination revealed 39 ICs (7.8%). All these ICs fell in a category of prostate cancer with clinical stage ≤ T2a and 2005 International Society of Urological Pathology Consensus Conference (ISUP) modified biopsy Gleason score ≤ 7. • Accordingly, we analysed predictors of IC in a subset cohort of 370 patients in this category. A multivariate logistic regression analysis revealed that 2005 ISUP modified biopsy Gleason score and CCL/core were independently significant predictors of IC. • We determined a threshold value of CCL/core of 0.20 mm for predicting IC using receiver operating characteristic analysis. • Based on these findings, we developed simple extended biopsy based criteria for predicting IC as follows: (i) PSA level of <20 ng/mL; (ii) Clinical stage ≤ T2a; (iii) 2005 ISUP modified biopsy Gleason score ≤ 6; (iv) CCL/core of <0.20 mm. • The specificity of the criteria was 91%, which was significantly higher than the value from a subset of criteria without item iv (P < 0.001). CONCLUSION: • We have developed extended biopsy based criteria for predicting IC incorporating the 2005 ISUP modified biopsy Gleason score and CCL/core.

Impact of C-reactive protein kinetics on survival of patients with advanced urothelial carcinoma treated by second-line chemotherapy with gemcitabine, etoposide and cisplatin.

OBJECTIVE: To assess the impact of C-reactive protein (CRP) kinetics, the effect of dynamic changes of CRP concentration on the survival of patients with locally advanced or metastatic urothelial carcinoma (UC) treated by single chemotherapeutic regimen including cisplatin was examined. PATIENTS AND METHODS: Eighty patients with advanced UC, who failed treatment of advanced UC with the first-line chemotherapy or who received perioperative treatment of neoadjuvant or adjuvant settings, were treated with gemcitabine, etoposide and cisplatin (GEP) as second-line chemotherapy. Patients were divided into three groups according to CRP kinetics based on baseline and nadir CRP concentrations. Patients whose baseline CRP levels were <5 mg/L, patients whose baseline CRP levels were ≥5 mg/L and normalized (<5 mg/L), and patients whose baseline CRP levels were ≥5 mg/L and never normalized were assigned to non-elevated, normalized and non-normalized CRP groups, respectively. The prognostic impact of CRP kinetics and the correlation between normalized CRP period and overall survival period were determined. RESULTS: In 46 (57%) of the 80 patients, CRP levels were elevated at the diagnosis of advanced UC. During treatment, after a median follow-up period of 12 months CRP levels were normalized in 24 (71%) of 34 patients, whereas CRP levels remained elevated in the remaining 10 patients. Overall survival rates were significantly different between the non-elevated, normalized, and non-normalized CRP groups (P < 0.001), with 1-year survival rates of 72, 51 and 14%, respectively. On multivariate analysis including Eastern Cooperative Oncology Group performance status, visceral metastasis, number of metastatic sites, previous definitive surgery, anaemia, baseline and nadir CRP levels (mg/L), and CRP kinetics status, CRP kinetics was an independent and significant factor for overall survival. The normalized CRP period was significantly correlated with the overall survival period in 52 patients who died. CONCLUSIONS: CRP kinetics is significantly associated with the prognosis and survival period of patients with advanced UC treated by chemotherapy. Although larger confirmatory studies are warranted to validate our results, CRP can potentially be a useful biomarker for patients with advanced UC.

Prognostic impact of C-reactive protein for determining overall survival of patients with castration-resistant prostate cancer treated with docetaxel.

OBJECTIVE: To verify the prognostic impact of C-reactive protein (CRP) for patients with castration-resistant prostate cancer (CRPC) treated with docetaxel in a single institution. METHODS: A group of 80 consecutive patients with CRPC were treated with docetaxel in our institution from January 2005 to May 2010. The patients received 75 mg/m(2) of docetaxel intravenously every 3 weeks. The prognostic value of all covariables, including CRP, was assessed using the Cox proportional hazard model. Risk stratification for overall survival was described from the results of the multivariable analysis. RESULTS: The median survival period for all patients was 14.5 months. The multivariable analysis showed that CRP and hemoglobin levels were independent prognostic factors for overall survival. Based on the presence of an elevated CRP concentration and/or a low hemoglobin level, all patients were stratified into 3 risk groups: those with no risk factors (low-risk group), those with 1 risk factor (intermediate-risk group), and those with 2 risk factors (high-risk group). The overall survival curves were clearly tiered according to the risk groups, with the 1-year overall survival rates being 86.3%, 60.5%, and 23.0% for the low-, intermediate-, and high-risk groups, respectively (P <.001). CONCLUSION: CRP is an independent prognostic factor for overall survival of patients with CRPC treated with docetaxel. Risk stratification based on CRP and hemoglobin could be helpful for estimating the overall survival.

Outcome of antegrade radical prostatectomy with intended wide resection in prostate cancer patients with a preoperative serum PSA level >100 ng/ml.

OBJECTIVE: It was the aim of this study to assess the outcome of prostate cancer patients with preoperative prostate-specific antigen (PSA) levels ≥100 ng/ml who were treated with antegrade radical prostatectomy with intended wide resection (aRP). PATIENTS AND METHODS: Eighteen patients who underwent aRP had an initial PSA level ≥100 ng/ml. Overall survival, disease-specific survival and biochemical progression-free survival (bPFS) rates were determined, and predictors of treatment outcome were examined. RESULTS: The median serum PSA level was 159.5 ng/ml. All patients but one had received neoadjuvant androgen deprivation therapy (ADT), while only 2 patients received adjuvant ADT. Five patients were classified as stage pT2, 6 as pT3a, 6 as pT3b and 1 as pT4. Four patients had locoregional lymph node metastases. Twelve patients developed PSA failure. Eight of them received salvage ADT. The estimated 10-year bPFS rate was 25.0% and the overall survival and disease-specific survival rates were 92.9 and 100%, respectively, at a median follow-up of 6 years. Multivariate analysis revealed only the clinical stage to be predictive of bPFS based on preoperative variables. On the other hand, surgical margin status, extracapsular extension and organ-confined disease were identified as being significant postoperative predictors. CONCLUSIONS: This study showed a comparatively satisfactory outcome for clinically non-metastatic prostate cancer with PSA levels ≥100 ng/ml treated by aRP.

Simple and effective local anesthesia for transperineal extended prostate biopsy: application to three-dimensional 26-core biopsy.

We developed a local anesthetic procedure for three-dimensional 26-core prostate biopsy (3D26PBx), a combination of transperineal 14-core biopsy (TP14PBx) and transrectal 12-core biopsy (TR12PBx). At first, a periapical triangle, confined by the levator ani, the rhabdosphincter and the external anal sphincter muscle, was made visible by transrectal ultrasound. After administration of 1 mL of 1%-lidocaine into the midline perineal skin 1.5 cm above the anus, we inserted a spinal needle toward the periapical triangle for injection of 1.5-2.0 mL of 1%-lidocaine and performed the TP14PBx. After administration of the periprostatic nerve block with 10 mL of 1%-lidocaine, we performed the TR12PBx. The efficacy of the procedure was evaluated prospectively in 45 consecutive men undergoing the 3D26PBx. The 3D26PBx was completed with just local anesthesia in all patients. The pain levels, assessed by an 11-point visual analog scale, were not different between the TP14PBx and the TR12PBx.

[Case of infective endocarditis diagnosed with renal infarction].

A 46-year-old woman with sudden on set strong right flank pain was transferred to our hospital with the diagnosis of right renal infarction. Cardiac ultrasonography revealed a vegetation on the posterior cusp of the mitral valve, and the renal infarction was thought to be caused by renal artery embolism from infective endocarditis. Since the vegetation remained after antimicrobial therapy as conservative management, the patient was surgically treated by mitral annuloplasty. It has been known that infective endocarditis can cause renal infarction. Infective endocarditis requires immediate and adequate treatment because of high mortality. Therefore, the appropriate diagnosis of infective endocarditis is needed for patients with renal infarction without any other disorder causing renal infarction.

A case of prostatic duct adenocarcinoma: its clinical significance in comparison with typical acinar adenocarcinoma.

We report a case of prostatic duct adenocarcinoma treated with radical prostatectomy. Advanced pathological stage (pT3bpN1) was beyond the prediction of the favorable preoperative parameters (cT1cN0, PSA 7.64 ng/ml). The main tumor of ductal adenocarcinoma was occupying the transitional zone and surrounded by scattered micro-foci of acinar adenocarcinoma. We identified coexistence of ductal and acinar adenocarcinoma cells side by side in the same gland. Pure ductal cancer cells were detected in the metastasized lymph node without acinar cancer cells. Strong staining of PSA and loss of p63 expression by both types of adenocarcinoma cells were confirmed immunohistochemically. We discuss the clinical significance of prostatic duct adenocarcinoma in comparision with typical acinar adenocarcinoma.

Human cathelicidin CAP18/LL-37 changes mast cell function toward innate immunity.

The antimicrobial peptide LL-37 is generated from skin keratinocytes during infection of Gram-negative bacteria and exerts a microbicidal effect. LL-37 also causes functional changes in mast cells. Mast cells in the skin are involved in the innate immune system response against microbial infections via Toll-like receptors (TLRs), such as TLR4, which that is known to recognize lipopolysaccharide (LPS), a bacterial component. Thus, in the present study, we examined the effects of LL-37 on the expression of TLRs and the generation of cytokines on mast cells, and considered functional changes in the host defense system against bacteria. We observed that LL-37 increased the level of TLR4 mRNA and TLR4 protein, and that LL-37 induced the release of IL-4, IL-5 and IL-1beta from mast cells. Cross-interaction between LL-37-triggered TLR4 augmentation and LL-37-inducible cytokine generation was also examined. Although the up-regulation of LL-37-inducible Th2 cytokines was cancelled by LPS, the augmentation of pro-inflammatory cytokine production was still observed. These findings indicate that LL-37 co-existing with the bacterial component switches mast cell function and directs human mast cells toward innate immunity. In conclusion, LL-37 may be a candidate modifier of the host defense against bacterial entry by serving as an alarm for sentinels such as mast cells.

[A case of secondary malignant lymphoma of the urinary bladder].

A 56-year-old man was admitted to our hospital for salvage chemotherapy of recurrent diffuse large B cell malignant lymphoma at clinical stage IIIb and which had been treated with 6 cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Computed tomography showed multiple tumors in the bladder after a cycle of ifosfamide, etoposide and mitoxantrone (MINE), but cystoscopy after the second cycle revealed a single non-papillary tumor about 1cm in diameter. After 3 cycles of MINE therapy, transurethral resection of bladder tumor was performed. At the time of the operation, the protruded lesion disappeared and there remained only a scar. Biopsy of the scar revealed malignant lymphoma infiltrated into the submucosal layer. Although the rate of the bladder involvement of malignant lymphoma reaches 3-20% in autopsy cases, it is very rare for a secondary malignant lymphoma of the urinary bladder to be diagnosed clinically. The prognosis of the secondary bladder lymphoma is much poorer than that of the primary one, because of the widespread dissemination of the disease at the time of diagnosis.