Combined tadalafil and α-blocker therapy for benign prostatic hyperplasia in patients with erectile dysfunction: a multicenter, prospective study

This prospective study evaluated the safety of tadalafil 5 mg taken once a day in terms of hypotensive side effects and whether it improves lower urinary tract symptoms (LUTS) and restores sexual function in patients with erectile dysfunction who are receiving concomitant α-blocker (AB) therapy for benign prostatic hyperplasia (BPH). A total of 158 LUTS/BPH patients receiving AB therapy for ≥3 months were given tadalafil 5 mg once a day. Before treatment with tadalafil (V1), and 4 weeks (V2) and 12 weeks (V3) after starting tadalafil, blood pressure, heart rate, International Prostate Symptom Score (IPSS), maximal urine flow rate (Qmax), postvoiding residual urine volume, and International Index of Erectile Function (IIEF-5) score were measured. Of the 158 LUTS/BPH patients, a total of 119 completed the trial. Blood pressure (systolic and diastolic) and heart rate did not change. IPSS and IIEF-5 scores improved significantly, but Qmax and postvoiding residual urine volume did not; however, in the 39 men with a low baseline Qmax (≤10 mL/s), Qmax rose significantly from 7.97 ± 1.44 mL/s (baseline) to 8.91 ± 1.60 mL/s (V3; P = .012). The remaining patients (baseline Qmax >10 mL/s) did not change. At V2 and V3, adverse side effects were observed in 10 men (7.30%) and 6 men (5.04%), respectively. Facial flushing was the most common adverse side effect (6 men at V2 and 4 men at V3), followed by headache (2 men each at V2 and V3) and dizziness (2 men at V2). Two patients dropped out of the study because of adverse side effects. In conclusion, tadalafil 5 mg once a day in combination with AB appeared to have few adverse effects on hypotensive events and can improve LUTS and restore sexual function.     

Surgical correction for supination loss following malunited radial fractures

We evaluated fourteen patients who had restricted supination as a major impairment related with a malunited radius fracture. All patients underwent an opening wedge corrective osteotomy, bone grafting, and volar plate fixation. Clinical results were assessed based on range of motion, visual analogue scale for pain, grip power, and a Modified Mayo Wrist Score. The mean supination increased from 24 degrees preoperatively to 71 degrees postoperatively (p < 0.01). Dorsiflexion range, grip power and pain score improved significantly after the operation. The mean value for the Modified Mayo Wrist score improved from 58.6 points to 83.9 points (p < 0.01). Radiological measurements showed that the degree of dorsal angulation decreased from a mean of 9.0 degrees to -2.5 degrees after the corrective osteotomy. This study demonstrated that a malunited radius fracture with dorsal angulation, even if the latter appears mild, can induce functional impairment due to limited range of supination. Supination can be restored by an appropriately performed corrective osteotomy.     

Factors related to the development of myelopathy in patients with cervical ossification of the posterior longitudinal ligament

This study evaluates factors related to myelopathic symptoms in patients with ossification of the posterior longitudinal ligament (OPLL). A total of 87 patients with OPLL were included. Of these, 53 (Group I) had no symptoms or presented with neck pain and radiculopathy and 34 (Group II) had myelopathic symptoms. Gender, age, and history of trauma were evaluated in the two groups. The range of movement of the cervical spine was measured using plain radiographs. The number of involved segments, type of OPLL, and maximal compression ratio were analysed using CT and signal change in the spinal cord was evaluated using MRI. The patients' age was found to be significant (p = 0.001). No difference was found between gender and the range of movement in the two groups. The maximum compression of the spinal canal showed a difference (p = 0.03). The signal change of the spinal cord was different between the two groups. In patients with OPLL of the cervical spine, myelopathic symptoms are not related to the range of movement or the number of involved segments.     

Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial

Background

Elderly patients with metastatic renal cell carcinoma (mRCC) may require special treatment considerations, particularly when comorbidities are present. An understanding of the efficacy and safety of targeted agents in elderly patients with mRCC is essential to provide individualized therapy.

Objective

To evaluate the efficacy and safety of everolimus in elderly patients (those ≥65 and ≥70 yr of age) enrolled in RECORD-1.

Design, setting, and participants

The multicenter randomized RECORD-1 phase 3 trial (Clinicaltrials.gov identifier, NCT00410124; http://www.clinicaltrials.gov) enrolled patients with mRCC who progressed during or within 6 mo of stopping sunitinib and/or sorafenib treatment (n = 416).

Intervention

Everolimus 10 mg once daily (n = 277) or placebo (n = 139) plus best supportive care. Treatment was continued until disease progression or unacceptable toxicity.

Measurements

Median progression-free survival (PFS), median overall survival (OS), and time to deterioration in Karnofsky performance status (TTD-KPS) were assessed using the Kaplan-Meier method; the log-rank test was used to compare treatment arms. Other outcomes evaluated included reduction in tumor burden, overall response rate (ORR), and safety.

Results and limitations

In RECORD-1, 36.8% of patients were ≥65 yr and 17.5% were ≥70 yr of age. PFS, OS, TTD-KPS, reduction in tumor burden, and ORR were similar in the elderly and the overall RECORD-1 population. Everolimus was generally well tolerated in elderly patients, and most adverse events were grade 1 or 2 in severity. The toxicity profile of everolimus was generally similar in older patients and the overall population; however, peripheral edema, cough, rash, and diarrhea were reported more frequently in the elderly regardless of treatment. The retrospective nature of the analyses was the major limitation.

Conclusions

Everolimus is effective and tolerable in elderly patients with mRCC. When selecting targeted therapies in these patients, the specific toxicity profile of each agent and any patient comorbidities should be considered.     

Anesthetic and recovery profiles of lidocaine versus mepivacaine for spinal anesthesia in patients undergoing outpatient orthopedic arthroscopic procedures

Study ObjectiveTo compare isobaric lidocaine and mepivacaine in outpatient arthroscopic surgery.DesignProspective, randomized, double-blinded study.SettingAmbulatory surgery center affiliated with an academic tertiary-care hospital.Patients84 adult, ASA physical status 1, 2, and 3 ambulatory patients, age 18-70 years, undergoing arthroscopic knee surgery.InterventionPatients were randomized to receive a combination spinal-epidural anesthetic using 80 mg of either isobaric 2% mepivacaine or isobaric 2% lidocaine. Patients also received a femoral 3-in-1 block with 0.5% bupivacaine applied to the affected extremity.MeasurementsDemographic data and level and duration of the block were recorded. The use of supplemental epidural anesthesia was noted along with frequency of bradycardia, hypotension, and episodes of nausea and vomiting. Duration of block and times to ambulation and voiding were recorded. Delayed variables, including fatigue, difficulty urinating, back pain, and transient neurologic symptoms (TNS) were obtained.Main ResultsNo demographic differences were noted between groups, and surgical duration was similar. Satisfactory anesthesia was achieved in all cases, with no differences noted in hypotension, bradycardia, nausea, or vomiting. Onset of sensory and motor block was similar. Duration of block before epidural supplementation was 94 ± 21 minutes with lidocaine versus 122 ± 23 minutes for mepivacaine (P < 0.011). Times to ambulation and voiding were longer in patients receiving mepivacaine but did not affect PACU stay. Twenty-four and 48-hour recovery was similar with no TNS symptoms reported.ConclusionNo major differences were noted between lidocaine and mepivacaine spinal anesthesia. Time to ambulation and voiding were longer in patients who received mepivacaine as was time to first dose of epidural catheter. Neither group had TNS symptoms. Lidocaine and mepivacaine are both appropriate spinal anesthetics for ambulatory orthopedic lower extremity procedures.     

Novel extraneural role of neurite outgrowth inhibitor A: modulation of osteoclastogenesis via positive feedback regulation of nuclear factor of activated T cell cytoplasmic 1

Osteoclasts are bone-resorbing cells differentiated from macrophage/monocyte lineage precursors upon receptor activator of NF-κB ligand (RANKL) stimulation. In a proteomic approach to identify proteins involved in osteoclastogenesis, we observed a dramatic increase in the expression of neurite outgrowth inhibitor A (Nogo-A) upon RANKL stimulation of mouse bone marrow macrophages (BMMs) in a nuclear factor of activated T cell cytoplasmic 1 (NFATc1)-dependent manner. The knockdown of Nogo-A in BMMs significantly reduced RANKL-dependent osteoclast differentiation accompanied by diminished NFATc1 induction, suggesting that a positive feedback mechanism is involved. Conversely, Nogo-A overexpression in BMMs as well as in RAW264.7 macrophages greatly augmented osteoclastogenesis, with concomitant increase in the NFATc1 induction. Both the mitogen-activated protein kinase (MAPK) pathway and calcium oscillation, which are central to RANKL-dependent NFATc1 activation and induction, were enhanced by Nogo-A. Finally, Nogo-A knockdown in mouse calvariae prevented interleukin 1 (IL-1)-induced bone loss. These findings not only reveal an unprecedented extraneural role of Nogo-A in osteoclastogenesis but also suggest a novel drug target against bone-lytic diseases.     

Misexpression of Dickkopf-1 in endothelial cells, but not in chondrocytes or hypertrophic chondrocytes, causes defects in endochondral ossification

Developing cartilage serves as a template for long-bone development during endochondral ossification. Although the coupling of cartilage and bone development with angiogenesis is an important regulatory step for endochondral ossification, the molecular mechanisms are poorly understood. One possible mechanism involves the action of Dickkopf (DKK), which is a family of soluble canonical Wnt antagonists with four members (DKK1-4). We initially observed opposite expression patterns of Dkk1 and Dkk2 during angiogenesis and chondrocyte differentiation: downregulation of Dkk1 and upregulation of Dkk2. We examined the in vivo role of Dkk1 and Dkk2 in linking cartilage/bone development and angiogenesis by generating transgenic (TG) mice that specifically express Dkk1 or Dkk2 in chondrocytes, hypertrophic chondrocytes, or endothelial cells. Despite specific expression pattern during cartilage development, chondrocyte- and hypertrophic chondrocyte-specific Dkk1 and Dkk2 TG mice showed normal developmental phenotypes. However, Dkk1 misexpression in endothelial cells resulted in defects of endochondral ossification and reduced skeletal size. The defects are caused by the inhibition of angiogenesis in developing bone and subsequent inhibition of apoptosis of hypertrophic chondrocytes and cartilage resorption.     

Mitral valve repair for double-orifice mitral valve with flail leaflet: the usefulness of real-time three-dimensional transesophageal echocardiography

We describe a 66-year-old man who required an operation for severe mitral regurgitation associated with a double-orifice mitral valve. Real-time 3-dimensional transesophageal echocardiography clearly demonstrated a double-orifice mitral valve with a central fibrous bridge. A flail posterior leaflet was observed on the anterolateral mitral valve orifice. Mitral valve repair using P1 triangular resection, anterolateral commissure plication, and ring annuloplasty with Duran band (Medtronic, Minneapolis, MN) was successfully performed. Postoperative real-time 3-dimensional transesophageal echocardiography demonstrated a double-orifice mitral valve without regurgitation or stenosis.     

Peritoneofascial Suture Method for Facilitating Loop Ileostomy Mobilization

Background

Ileostomy closure is a minor procedure and is performed through a small peristomal incision. However, a hard adhesion increases the technical difficulty. A peritoneofascial suture (PFS) will reduce the adhesion layers of the abdominal wall. This study was performed to evaluate whether the PFS method may decrease the extent of adhesions between the bowel and the abdominal wall opening and facilitate ileostomy mobilization.

Methods

Forty-two patients (24 males and 18 females) with a mean age of 57?years (range?=?31–80?years) and who were undergoing ileostomy closure were enrolled. The PFS group and the conventional group had 18 and 24 patients, respectively. The intraoperative findings such as degree of adhesion, mobilization time, and associated bowel injury were analyzed.

Results

The thickness of the abdominal wall and the rectus abdominis was similar in both groups. The overall operation time was shorter in the PFS group than in the conventional group (50.9 vs. 80.4?min, respectively, p?=?0.001). The ileostomy mobilization time was also shorter in the PFS group than in the conventional group (18.9 vs. 44.7?min, respectively, p?p?=?0.013). Bowel injury during mobilization was more common in the conventional group than in the PFS group (50.0?% vs. 16.7?%, respectively, p?=?0.053).

Conclusions

The peritoneofascial suture method is a simple procedure, and it may facilitate ileostomy mobilization by decreasing adhesion layers. To confirm the technical advantage of this method a randomized study will be needed.     

Streptococcus dysgalactiae subspecies dysgalactiae infection after total knee arthroplasty: a case report

Streptococcus dysgalactiae subspecies dysgalactiae (SDSD), Lancefield group C streptococcus, is an animal pathogen which often causes pyogenic infection in domestic animals. Human infection by SDSD has been reported as a cellulitis on the upper arm, but a prosthetic joint infection caused by SDSD after total knee arthroplasty (TKA) has not yet been reported in the literature demonstrating that its clinical manifestation and management have not been well established. In this case report, we aimed to present a case of SDSD prosthetic joint infection after TKA, which was successfully treated by two-stage re-implantation with an application of antibiotic-impregnated cement spacer.