Significant accumulation of KRAS mutations in bronchiolar metaplasia-associated honeycomb lesions of interstitial pneumonia

Interstitial pneumonia (IP) is a major risk factor for lung adenocarcinoma (LADC). IP-related LADC predominantly develops in the bronchiolar metaplasia lining in honeycomb lesions. Kirsten rat sarcoma virus (KRAS) is the most common oncogene mutated in IP-related LADC. The present study examined the metaplastic epithelia in honeycomb lesions for KRAS mutations using digital droplet polymerase chain reaction (ddPCR), a sensitive method used to detect infrequent mutations. Significantly higher KRAS mutation variant allele frequencies (VAFs) were detected in the metaplastic lung epithelia from 13 patients with IP compared with those in 46 non-lesioned lung samples from patients without IP (G12V, P=0.0004, G12C, P=0.0181, and G12A, P=0.0234; Mann Whitney U test). Multivariate analyses revealed that higher KRAS G12V (logistic regression model; P=0.0133, odds ratio=7.11) and G12C (P=0.0191, odds ratio=5.81) VAFs in patients with IP were independent of confounding variables, such as smoking and age. In patients with IP, metaplastic epithelia exhibited significantly higher KRAS G12V and G12C VAFs compared with the non-lesioned counterparts (paired t-test; G12V, P=0.0158, G12C, P=0.0465). These results suggested that IP could increase KRAS mutations and supported the hypothesis that bronchiolar metaplasia could be a precursor for IP-related LADC.     

Influence of Altered Knee Angle on Electromyographic Activity of Hamstring Muscles Between Nordic Hamstring Exercise and Nordic Hamstring Exercise with Incline Slope Lower Leg Board

BackgroundPrevious studies have shown that performing the Nordic hamstring exercise (NHE) with different board slope angles can affect hamstring activation. However, changes in muscle length with different board slopes can alter joint angles leading to the moment arm (MA) at the knee changing during the NHE.PurposeThis study aimed to investigate the influence of changing muscle length on hamstring electromyographic activity during an isometric NHE, while maintaining an equal moment arm.Study DesignA crossover study designMethodsSixteen male volunteers performed two types of conventional NHE, one with knees on the floor (NHE) and one with the legs placed upon an incline slope of a lower leg board (NHEB). To compare between the conventional and inclined NHE, the moment arm at the knee was calculated to be equal by an examiner holding the lower legs at points marked at 77% and 94% of the length of the lower leg. The four sub-groups comprised of: 1) NHE-77%, 2) NHE-94%, 3) NHEB-77%, and 4) NHEB-94%. The hamstring EMG activity was measured at the biceps femoris long head (BFlh) and at the semitendinosus (ST) and related compensatory muscles. The RMS data were normalized as a percentage of the maximum isometric values (normalized EMG [nEMG]). Significant main effects findings were followed up with Tukey’s post-hoc test using SPSS software and statistical significance was set at the p < 0.05 level.ResultsThe BFlh EMG activity values for NHE-77% were significantly higher than those for NHE-94% (p= 0.036) and NHEB-77% (p < 0.001), respectively, while ST during NHE-77% was significantly higher only in NHEB-77% (p < 0.001). In addition, NHEB-94% was significantly greater than NHEB-77% for both BFlh (p < 0.001) and ST (p < 0.001).ConclusionThese results indicate that hamstring electromyographic activity is decreased when the hamstring muscle is lengthened during the Nordic hamstring exercise.Level of Evidence3     

Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthritis Receiving Methotrexate: A Single-center Retrospective Study

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.     

Two cases of urinary retention secondary to aseptic meningitis]

We report two rare cases of urinary retention secondary to aseptic meningitis. Case I was in a 13-year-old boy admitted to the pediatric department due to aseptic meningitis. Eight days after his admission, urinary retention developed and cystometry showed atonic bladder. Case 2 was in a 18-year-old woman consulted the urological department with a chief complaint of urinary retention accompanied with high fever, headache and vomiting. The spinal fluid examination and cystometry revealed aseptic meningitis and atonic bladder, respectively. In both cases, the patients were treated with conservative therapy and bladder dysfunction was resolved after a few weeks. Eleven cases of urinary retention secondary to aseptic meningitis have been reported in the previous literature.     

Distribution of osteopontin and calprotectin as matrix protein in calcium-containing stone

We recently reported that osteopontin (OPN) and calprotectin (CPT) are present in the matrix of urinary calcium stones, and that OPN mRNA is expressed in the renal distal tubular cells. In the present study, we examined the immunohistochemical distributions of OPN and CPT in urinary stones. The stones used in this study were passed spontaneously from the upper urinary tract. One half of each of the stones was analyzed with an infrared spectrophotometer, and were shown to be comprised of calcium oxalate, calcium phosphate, uric acid and cystine. The other half of each stone was immersed in tetrasodium ethylenediamine-tetraacetate (EDTA) solution. The half-stones were embedded in paraffin and cut into 5-μm sections. The avidin-biotin-peroxidase complex technique was employed. A monoclonal antibody to human milk-derived OPN and a monoclonal antibody to human granulocyte-derived CPT were used as primary antibodies. The immunochemical study using the OPN and CPT antibodies showed positive staining of the matrix of the urinary calcium stones. The stones showed staining in two distinct zones: a core area was stained with randomly aggregated OPN and CPT, and peripheral layers were stained in concentric circles. On the basis of our observations, it is reasonable to presume that OPN and CPT play roles as the matrix in the structure of urinary calcium stones. Received: 24 February 1998 / Accepted: 28 January 1999     

Fibroma of tendon sheath originating from the knee joint capsule

We present a rare case of fibroma of the tendon sheath originating from the posterior joint capsule of the knee in a 50-year-old man. Magnetic resonance (MR) imaging revealed a lesion posterior to the medial femoral condyle. The lesion showed hypointensity on all T1-weighted, T2-weighted, short tau inversion recovery (STIR), and contrast-enhanced T1-weighted images. Plain computed tomographic (CT) scans showed a lesion with isodensity to muscle. The lesion showed no enhancement on postcontrast CT scans.     

Laparoscopic pancreaticoduodenectomy combined with minilaparotomy

Laparoscopic pancreatic surgery is evolving rapidly; however, the surgical treatment of periampullary tumors is still fraught with challenges, such as technical difficulty and the appropriateness of oncologic treatment for these patients. We describe how we performed laparoscopic pancreaticoduodenectomy (LPD) combined with minilaparotomy successfully in six consecutive patients. This procedure consisted of two surgical phases: safe laparoscopic surgery, including the Kocher maneuver, tunneling behind the pancreatic neck, and dissecting along the uncinate process with magnified vision; and a secure open approach with complete skeletonization of the hepatoduodenal ligament and alimentary tract reconstruction, performed similarly to conventional pancreaticoduodenectomy, under direct visualization through the minilaparotomy. By performing this procedure, we combined a safe and secure minilaparotomy approach under direct vision with a less invasive laparoscopic approach providing a magnified image. Our experience demonstrates that LPD combined with minilaparotomy is technically feasible for selected patients with periampullary tumors.     

Epidural ropivacaine anesthesia decreases the bispectral index during the awake phase and sevoflurane general anesthesia

The sedative effects of epidural anesthesia without volatile and IV anesthetics and quantification of the degree of epidural anesthesia-induced sedation have not been investigated. In the current study we evaluated the effects of epidural anesthesia on the bispectral index (BIS) during the awake phase and during general anesthesia. After placing the epidural catheter, the patients were randomly allocated to 2 groups receiving either 5 mL of epidural saline (group S) or the same volume of 0.75% ropivacaine (group R). The BIS measurements during the awake phase were performed at 7, 12, 13, 14, 22, and 23 min after the epidural injection. General anesthesia was then induced with propofol and vecuronium and maintained with 0.75% sevoflurane. From approximately 10 min after tracheal intubation, the BIS measurements were made at 1-min intervals for 10 min. The BIS during the awake phase was significantly lower in group R than in group S (P < 0.05). The BIS during general anesthesia was significantly lower in group R than in group S (P < 0.0001). Epidural anesthesia decreased the BIS during the awake phase and during general anesthesia. The decrease of the BIS associated with epidural anesthesia was more prominent during general anesthesia than during the awake phase.     

Results of laparoscopic liver resection: retrospective study of 68 patients

Background  Although an increasing number of reports and publications have dealt with the laparoscopic approach to liver resection, this procedure remains uncommon, and its feasibility, safety and effectiveness are still not established. There are few reports of the advantages of this approach on postoperative recovery. Methods  From December 1997 to March 2007, laparoscopic hepatic resection were performed in 68 patients. Results  There were 52 malignant tumors (36 hepatocellular carcinomas, three intrahepatic cholangiocarcinomas, one cystadenocarcinoma, liver metastases from ten colorectal carcinomas and two other organs) and 16 benign lesions among our 68 patients. Fifteen patients with hepatocellular carcinoma had cirrhosis. The mean tumor size was 3.1 ± 1.8 cm (range 1.0–14.0 cm), and the tumors were located in every liver segment except segment I. Liver resection was anatomical in 17 patients and consisted of a lobectomy in four patients and a lateral segmentectomy in 13 patients. Non-anatomical resections were performed in 51 patients. The operative time was 214 ± 93 min. Mean blood loss was 393 ± 564 g. A hand-assisted laparoscopic method or mini-laparotomy method was required in 35 patients (51.4%). Operative complications occurred mainly in our early cases and included three patients (4.4%) with operative bleeding, 2 of whom (2.9%) requiring a conversion to open surgery. Postoperative complications occurred in seven patients (10.0%), and two of then eventually required a re-operation. The mean hospital stay was 17 days. There were no complications in the more recent cases. Conclusions  The laparoscopic approach for liver tumors is feasible, if the indication is carefully selected. The safety of this procedure depends on the surgical experience of the surgeon and team and the availability of the necessary technology.