Preoperative planning system for surgical robotics setup with kinematics and haptics

Recently, some useful robotic surgical systems have been developed and applied in many surgical situations. Systems such as the da Vinci surgical system of Intuitive Surgical Inc., which facilitates minimally invasive surgery with increased dexterity, are commercially available. Preoperative simulation and planning of surgical robot setups should accompany advanced robotic surgery if their advantages are to be further pursued. Feedback from the planning system will play an essential role in computer-aided robotic surgery in addition to preoperative detailed geometric information from patient CT/MRI images. Surgical robot setup simulation systems for appropriate trocar site placement have been developed especially for abdominal surgery. The motion of the surgical robot can be simulated and rehearsed with kinematic constraints at the trocar site, and the inverse-kinematics of the robot. Results from simulation using clinical patient data verify the effectiveness of the proposed system.     

Strategies for targeting the gingipain secretion system of Porphyromonas gingivalis

Porphyromonas gingivalis is considered the most important etiologic agent in chronic periodontitis. P. gingivalis secretes several proteases that promote disease progression by degrading host cells and proteins. P. gingivalis is asaccharolytic and uses peptides as an energy source; therefore, peptide fragments arising from the digestion of host proteins are important for multiplication of this bacterium. Gingipains are secretory endoproteases of P. gingivalis with trypsin-like activity and are particularly important for both degradation of host proteins and P. gingivalis growth. Conventional minimal media for P. gingivalis are indispensable for gaining further understanding of gingipain biogenesis, but media studies sometimes suffer from poor reproducibility. We developed an improved minimal medium for P. gingivalis, GA, which includes a mixture of immunoglobulin G and bovine serum albumin as the sole energy sources. Recent advances in our understanding of the secretion of gingipains have been remarkable. We identified three novel proteins, Sov (PG810-PG809), PG27, and PG534, which are essential for the secretion of gingipains and the activity of the gingipains. By using GA medium, we showed that both Sov and PG27 are essential for asaccharolytic growth of P. gingivalis. Therefore, in addition to gingipains, which themselves are virulence/proliferation factors, other factors participating in the secretion of gingipains may also be important targets of new drugs to cure periodontitis.     

Retinal circulatory changes associated with interferon-induced retinopathy in patients with hepatitis C

PURPOSE: To evaluate the effect of interferon (IFN) therapy on retinal microcirculation. METHODS: Thirty-six patients with chronic hepatitis C who were treated with high-dose IFN were included in this prospective study. The changes in vessel diameter and blood velocity were measured, and the retinal blood flow (RBF) and wall shear rate (WSR) were calculated in the retinal arteries before and 2, 4, 8, 16, and 24 weeks after IFN therapy by using laser Doppler velocimetry. RESULTS: Retinal blood velocity, RBF, and WSR significantly (P < 0.0001) increased in all patients, as early as 2 weeks after IFN therapy. The increase in RBF was independently correlated with a decrease in the red blood cell count. In 22 (61%) of the 36 patients asymptomatic retinopathy developed during treatment. In patients with retinopathy, the blood velocity and WSR increased, but the vessel diameter did not change, whereas the vessel diameter increased but the blood velocity and WSR did not change in patients without retinopathy 2 weeks after IFN therapy. Multiple logistic regression analysis showed that patient age and the change in WSR at week 2 were risk factors for the development of IFN-induced retinopathy. CONCLUSIONS: RBF increases in association with IFN therapy in patients with chronic hepatitis C. In addition, the increased WSR in patients with retinopathy indicates that retinal vascular endothelial dysfunction may be associated with IFN-induced retinopathy, because wall shear stress should be constant under physiologic conditions.     

Severe form of familial exudative vitreoretinopathy caused by homozygous R417Q mutation in frizzled-4 gene

PURPOSE: To report the clinical features of a patient with familial exudative vitreoretinopathy (FEVR) associated with homozygous R417Q mutation in the frizzled-4 gene (FZD4). METHODS: Clinical examination and mutation analysis by direct sequencing. RESULTS: A five-month-old girl was found to have leukocoria associated with retrolental fibroplasia in the right eye and a severe falciform retinal fold in the left eye. Mutational analysis revealed a homozygous R417Q mutation in the FZD4 gene. Her parents who carried the same mutation heterozygously exhibited milder ocular phenotype. CONCLUSIONS: Homozygous state for the FZD4 gene is possibly involved in the severity of the FEVR phenotype.     

Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy

PURPOSE: To search for mutations in the Norrie disease gene (NDP) in Japanese patients with familial exudative vitreoretinopathy (FEVR) and Norrie disease (ND) and to delineate the mutation-associated clinical features. METHODS: Direct sequencing after polymerase chain reaction of all exons of the NDP gene was performed on blood collected from 62 probands (31 familial and 31 simplex) with FEVR, from 3 probands with ND, and from some of their family members. The clinical symptoms and signs in the patients with mutations were assessed. X-inactivation in the female carriers was examined in three FEVR families by using leukocyte DNA. RESULTS: Four novel mutations-I18K, K54N, R115L, and IVS2-1G-->A-and one reported mutation, R97P, in the NDP gene were identified in six families. The severity of vitreoretinopathy varied among these patients. Three probands with either K54N or R115L had typical features of FEVR, whereas the proband with R97P had those of ND. Families with IVS2-1G-->A exhibited either ND or FEVR characteristics. A proband with I18K presented with significant phenotypic heterogeneity between the two eyes. In addition, affected female carriers in a family harboring the K54N mutation presented with different degrees of vascular abnormalities in the periphery of the retina. X-inactivation profiles indicated that the skewing was not significantly different between affected and unaffected women. CONCLUSIONS: These observations indicate that mutations of the NDP gene can cause ND and 6% of FEVR cases in the Japanese population. The X-inactivation assay with leukocytes may not be predictive of the presence of a mutation in affected female carriers.     

Evaluation of apremilast,an oral phosphodiesterase 4 inhibitor,for refractory cutaneous dermatomyositis: A phase 1b clinical trial

Dermatomyositis, an idiopathic inflammatory myopathy, is characterized by cutaneous itchy manifestations, which are frequently refractory and recurrent even after intensive immunosuppressive treatments. To evaluate the effectiveness and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in treating skin-dominant dermatomyositis in which myositis and interstitial lung disease are absent or in remission, we performed this prospective, single-arm, interventional study. A total of five Japanese patients (one male and four females, median [range] age, 64 [37–71] years) with refractory dermatomyositis-associated cutaneous manifestations were recruited and treated with a 12-week course of oral apremilast. Among five enrolled patients, three experienced diarrhea with full-dose apremilast (30 mg twice daily), two of whom withdrew from the study and recovered quickly afterwards. A total of three evaluable female patients (median [range] age, 65 [64–71] years) received apremilast treatment for 12 weeks. A 39.4% reduction from baseline Cutaneous Dermatomyositis Disease Area and Severity Index total activity score, but not the damage score, at week 12 was observed in all three patients. Visual analog scale of itching, and quality of life by Dermatology Life Quality Index were slightly improved in one and two apremilast-treated patients, respectively. As apremilast was effective, with expected and recoverable digestive adverse events (diarrhea), in patients with refractory and recurrent dermatomyositis-associated cutaneous manifestations in this first phase Ib study, it can be suggested as a possible treatment when aggressive immunosuppressive therapies with high-dose systemic corticosteroid and/or immunosuppressive agents for other manifestations, myositis, and interstitial lung disease, are not required.     

Factors associated with frailty in Japanese patients with rheumatoid arthritis: results from the Institute of Rheumatology Rheumatoid Arthritis cohort study

Clinical Rheumatology - This study aimed to evaluate the prevalence of, and the factors associated with, frailty in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in...     

Mild decrease in heart rate during early phase of targeted temperature management following tachycardia on admission is associated with unfavorable neurological outcomes after severe traumatic brain injury: a post hoc analysis of a multicenter randomized controlled trial

Background

The association between isolated admission heart rate (HR) and prognosis has been discussed, but not that between gross HR change and neurological outcome in patients with severe traumatic brain injury (TBI). In the acute phase of severe TBI, HR is influenced by several factors (e.g., pain, sympathetic activation, hypovolemia, fever, body temperature). Therefore, admission HR and gross HR change should be examined in patients with TBI treated with a well-designed protocol, such as was done in the Brain Hypothermia (B-HYPO) Study.

Methods

This was a post hoc analysis of the B-HYPO Study, which was conducted as a prospective, multicenter, randomized controlled trial in patients with severe TBI receiving mild therapeutic hypothermia (MTH; 32.0?°C–34.0?°C) or fever control (35.5?°C–37.0?°C) in Japan. Patients with MTH were examined, and HR change (%HR) in the early MTH phase was calculated as follows: [admission HR – HR at day 1]/admission HR?×?100. Patients were divided into six groups, using admission HR (<?80, 80–99, ≤?100) and median of %HR; i.e., group (Admission HR <?80 and %HR ≥?18.6); group (Admission HR <?80 and %HR <?18.6); group (Admission HR 80–99 and %HR ≥?18.6); group (Admission HR 80–99 and %HR <?18.6); group (Admission HR ≥100 and %HR ≥?18.6); and group (Admission HR ≥100 and %HR <?18.6). The primary outcome was an adjusted predicted probability of unfavorable neurological outcome at 6 months after TBI according to Glasgow Outcome Scale score, which is a measure of functional recovery and defined as severe disability, persistent vegetative state, and death.

Results

Overall, 79 patients with MTH (52.7% of the original trial) were examined; among these, unfavorable neurological outcomes were observed in 53.2%. Among all the groups, group (Admission HR ≥100 and %HR <?18.6) exhibited the highest proportion of unfavorable outcomes, and 82.3% of patients had an adjusted predicted probability of unfavorable outcomes, whereas those in group (Admission HR <?80 and %HR ≥?18.6) developed only 22.8% (p?=?0.04).

Conclusions

Mild HR decrease during the early phase of targeted temperature management following tachycardia at admission can be associated with unfavorable neurological outcomes after severe TBI.