Network meta-analysis of the analgesic effectiveness of regional anaesthesia techniques for anterior cruciate ligament reconstruction.

Anterior cruciate ligament reconstruction can cause moderate to severe acute postoperative pain. Despite advances in our understanding of knee innervation, consensus regarding the most effective regional anaesthesia techniques for this surgical population is lacking. This network meta-analysis compared effectiveness of regional anaesthesia techniques used to provide analgesia for anterior cruciate ligament reconstruction. Randomised trials examining regional anaesthesia techniques for analgesia following anterior cruciate ligament reconstruction were sought. The primary outcome was opioid consumption during the first 24 h postoperatively. Secondary outcomes were: rest pain at 0, 6, 12 and 24 h; area under the curve of pain over 24 h; and opioid-related adverse effects and functional recovery. Network meta-analysis was conducted using a frequentist approach. A total of 57 trials (4069 patients) investigating femoral nerve block, sciatic nerve block, adductor canal block, local anaesthetic infiltration, graft-donor site infiltration and systemic analgesia alone (control) were included. For opioid consumption, all regional anaesthesia techniques were superior to systemic analgesia alone, but differences between regional techniques were not significant. Single-injection femoral nerve block combined with sciatic nerve block had the highest p value probability for reducing postoperative opioid consumption and area under the curve for pain severity over 24 h (78% and 90%, respectively). Continuous femoral nerve block had the highest probability (87%) of reducing opioid-related adverse effects, while local infiltration analgesia had the highest probability (88%) of optimising functional recovery. In contrast, systemic analgesia, local infiltration analgesia and adductor canal block were each poor performers across all analgesic outcomes. Regional anaesthesia techniques that target both the femoral and sciatic nerve distributions, namely a combination of single-injection nerve blocks, provide the most consistent analgesic benefits for anterior cruciate ligament reconstruction compared with all other techniques but will most likely impair postoperative function. Importantly, adductor canal block, local infiltration analgesia and systemic analgesia alone each perform poorly for acute pain management following anterior cruciate ligament reconstruction.

Long-term efficacy, safety, and tolerability of a subcutaneous immunoglobulin 16.5% (cutaquig®) in the treatment of patients with primary immunodeficiencies.

A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig®) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years). Seventy-five patients received 4462 infusions during up to 70 weeks of follow-up in the main study and 27 patients received 2777 infusions during up to 168 weeks of follow-up in the extension. In the main study, there were no serious bacterial infections (SBIs), and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5). One SBI was recorded in the extension, for an SBI rate of 0.02 (upper 99% CI 0.19). The annual rate of all infections over the duration of the extension study was 2.2 (95% CI 1.2, 3.9). Only 15.0% (1085) of 7239 infusions were associated with infusion site reactions (ISRs), leaving 85.0% (6153) of infusions without reactions. The majority of ISRs were mild and transient. ISR incidence decreased over time, from 36.9% to 16% during the main study and from 9% to 2.3% during the extension. The incidence of related systemic adverse events was 14.7% in the main study and 7.4% in the extension. In conclusion, this prospective, long-term study with cutaquig showed maintained efficacy and low rates of local and systemic adverse reactions in PID patients over up to 238 weeks of follow-up.

Analgesic benefits of the quadratus lumborum block in total hip arthroplasty: a systematic review and meta-analysis.

The quadratus lumborum block (QLB) is reported to reduce pain and improve function following total hip arthroplasty; however, randomised controlled trials evaluating the benefits of adding this block to general or spinal anaesthesia in this population are conflicting. We performed a systematic review seeking randomised controlled trials investigating QLB benefits for total hip arthroplasty, stratifying comparisons regarding the addition of QLB to either general or spinal anaesthesia. The primary outcome was 24-h area under the curve (AUC) pain score. Pain scores were interpreted in the context of a population-specific minimal clinically important difference of 1.86 cm on a 10-cm visual analogue scale, or an AUC pain score of 5.58 cm.h. Secondary outcomes included analgesic consumption, functional recovery and opioid-related side-effects. In all, 18 trials (1318 patients) were included. Adding QLB to general or spinal anaesthesia improved 24-h AUC rest pain scores by a mean difference (95%CI) of -3.56 cm.h (-6.70 to -0.42; p = 0.034) and - 4.19 cm.h (-7.20 to -1.18; p = 0.014), respectively. These improvements failed to reach the pre-determined minimal clinically important difference, as did the reduction in analgesic consumption. Quadratus lumborum block improved functional recovery for general, but not spinal, anaesthesia. Opioid-related side-effects were reduced with QLB regardless of anaesthetic modality. Low-to-moderate quality evidence suggests that the extent to which adding QLB to either general or spinal anaesthesia reduces postoperative pain and opioid consumption after total hip arthroplasty is statistically significant but may be clinically unimportant for most patients. However, adding QLB to general anaesthesia might enhance functional recovery. Taken together, our findings do not support the routine use of QLB as part of multimodal analgesic regimens for total hip arthroplasty.

Integrin-mediated interactions with a laminin-presenting substrate modulate biosynthesis and phenotypic expression for cells of the human nucleus pulposus.

With aging and pathology, cells of the nucleus pulposus (NP) de-differentiate towards a fibroblast-like phenotype, a change that contributes to degeneration of the intervertebral disc (IVD). Laminin isoforms are a component of the NP extracellular matrix during development but largely disappear in the adult NP tissue. Exposing human adult NP cells to hydrogels made from PEGylated-laminin-111 (PEGLM) has been shown to regulate NP cell behaviors and promote cells to assume a biosynthetically active state with gene/protein expression and morphology consistent with those observed in juvenile NP cells. However, the mechanism regulating this effect has remained unknown. In the present study, the integrin subunits that promote adult degenerative NP cell interactions with laminin-111 are identified by performing integrin blocking studies along with assays of intracellular signaling and cell phenotype. The findings indicate that integrin α3 is a primary regulator of cell attachment to laminin and is associated with phosphorylation of signaling molecules downstream of integrin engagement (ERK 1/2 and GSK3ß). Sustained effects of blocking integrin α3 were also demonstrated including decreased expression of phenotypic markers, reduced biosynthesis, and altered cytoskeletal organization. Furthermore, blocking both integrin α3 and additional integrin subunits elicited changes in cell clustering, but did not alter the phenotype of single cells. These findings reveal that integrin- mediated interactions through integrin α3 are critical in the process by which NP cells sense and alter phenotype in response to culture upon laminin and further suggest that targeting integrin α3 has potential for reversing or slowing degenerative changes to the NP cell.

Towards universal ambient ionization: direct elemental analysis of solid substrates using microwave plasma ionization.

A microwave plasma was used for direct ambient ionization mass spectrometry of solid substrates, rapidly yielding atomic spectra without sample digestion or pre-treatment. Further, molecular spectra for the organic components of the substrate were obtained simultaneously, in an ambient ionization format. Initial characterization of the microwave plasma coupling to an ion trap mass spectrometer was carried out using solution standards and a microwave plasma torch (MPT) configuration. The configuration of the microwave plasma was then optimized for ambient ionization. The atomic and organic composition for samples applicable to nuclear and conventional forensic screening, including explosive/radionuclide mixtures and inorganic/organic gunshot residue component mixtures were successfully determined. The technologies employed are readily fieldable; the feasibility of a multimode ion source that could be coupled with a portable ion trap mass spectrometer for rapid, on-site, elemental, isotopic, and molecular screening of samples is demonstrated.

Publisher Correction: Rapid Thermal Processing to Enhance Steel Toughness.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Rapid Thermal Processing to Enhance Steel Toughness.

Quenching and Tempering (Q&T) has been utilized for decades to alter steel mechanical properties, particularly strength and toughness. While tempering typically increases toughness, a well-established phenomenon called tempered martensite embrittlement (TME) is known to occur during conventional Q&T. Here we show that short-time, rapid tempering can overcome TME to produce unprecedented property combinations that cannot be attained by conventional Q&T. Toughness is enhanced over 43% at a strength level of 1.7 GPa and strength is improved over 0.5 GPa at an impact toughness of 30 J. We also show that hardness and the tempering parameter (TP), developed by Holloman and Jaffe in 1945 and ubiquitous within the field, is insufficient for characterizing measured strengths, toughnesses, and microstructural conditions after rapid processing. Rapid tempering by energy-saving manufacturing processes like induction heating creates the opportunity for new Q&T steels for energy, defense, and transportation applications.

A stochastic numerical model of breast cancer growth that simulates clinical data.

A new stochastic numerical model of breast cancer growth is developed. First, the model suggests that Gompertzian kinetics does apply but that from time to time, in random fashion, there occurs a spontaneous change in the growth rate or rate of decay of growth, such that the overall growth pattern occurs in a stepwise fashion. According to the model, the average time for the tumor burden to increase from one cell to detection is probably in the range of 8 years. Secondly, the model suggests that there is a linear relationship between the number of axillary lymph nodes positive for metastasis at diagnosis and the number of other metastatic sites. This can be described mathematically by the equation S = 0.24 + 0.35N where S is the number of other metastatic sites and N is the number of positive lymph nodes. The model has been verified by simulating three data sets: (a) the survival times of untreated breast cancer patients as described by Bloom et al. [Br. Med. J., 2: 213-221, 1962]; (b) the growth rates of breast cancers immediately prior to diagnosis as described by Heuser and Spratt [Cancer (Phila.), 43: 1888-1894, 1979]; and (c) the disease-free survival time postmastectomy as described by Fisher et al. [Surg. Gynecol. Obstet., 140: 528-534, 1975]. This model could have implications concerning the overall treatment rationale for breast cancer.

Physiological studies of whole-body hyperthermia of dogs.

Whole body hyperthermia to 42 degrees C was induced in five normal beagles, using a humidity- and temperature-controlled chamber. Core temperatures of 41.2-43.0 degrees C were achieved in 50 min and maintained for 60 min. Cardiopulmonary responses included marked tachypnea and tachycardia. Blood gases underwent progressive drops in both PO2 (mean, 117 torr) and PCO2 (mean, 22 torr), suggesting the possibility of the development of a diffusion barrier during heating. Increased anion gaps in the face of respiratory alkalosis indicated that a metabolic acidosis developed in the heated dogs. Transient but significant drops in serum potassium and phosphorus were also observed during hyperthermia. Other physiological data, including serum chemistries, complete blood count, colony-forming units, and urine electrolyte excretion, did not change significantly.

Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group.

A total of 353 patients with previously untreated small-cell lung cancer (SCLC) were accrued in this multicenter trial. Patients were randomly assigned to receive one of the following three regimens: cyclophosphamide 1,000 mg/m2 intravenously (IV) day 1, vincristine 1.4 mg/m2 IV day 1, and etoposide 50 mg/m2 IV day 1, followed by etoposide 100 mg/m2/day orally days 2 through 5 (CEV); cyclophosphamide 1,000 mg/m2 IV day 1, vincristine 1.4 mg/m2 IV day 1, and doxorubicin 50 mg/m2 IV day 1 (CAV); cyclophosphamide 2,000 mg/m2 day 1 and vincristine 1.4 mg/m2 IV day 1 (CV). Cycles were repeated every 3 weeks. Treatment groups were comparable with respect to extent of disease, age, sex, performance status, and metastatic sites. No significant differences in response rates, response duration, or survival could be detected in limited disease, although there appeared to be a trend favoring CEV. Among extensive-disease patients, response duration on the CEV regimen was longer than on the CV regimen or the CAV program (P less than .001). The superiority of the CEV regimen was also demonstrated in the survival analysis in which differences attained statistical significance (P = .01). In this group the median survival was increased from 29 weeks on CV to 31 weeks on CAV and 39 weeks on CEV. Myelosuppression was the most frequent toxicity. It was more severe with CV than CEV or CAV. Most nonhematologic side effects were comparable among the three treatment groups. However, the high doses of cyclophosphamide in the CV regimen produced a higher incidence of hemorrhagic cystitis than in the CEV or CAV programs (P less than .001). Cardiotoxicity only occurred in the CAV group (P = .05). The addition of etoposide to the CV regimen resulted in significantly longer response duration and survival without increased toxicity. Similarly, the substitution of etoposide for the doxorubicin in the CAV regimen was associated with prolonged survival and reduced cardiotoxicity.

AOFAS member experience with computerization of the office.

BACKGROUND: The combination of the implementation of the Healthcare Information Portability and Accountability Act (HIPAA) and the widespread publicity surrounding the report by the Institute of Medicine on preventable medical errors has increased interest of AOFAS members in the use of office-based electronic medical record (EMR) systems. Despite the large number of vendors for office-based EMR systems, little has been written to guide orthopaedists in the selection and installation of EMR systems. METHODS: A web-based AOFAS member survey was undertaken in the Spring of 2003, for the purpose of discovering EMR-related issues that are of most concern. Several questions were open-ended, so as to obtain the broadest set of answers. All responses were manually reviewed, collated, analyzed. RESULTS: The 130 respondents were evenly distributed in age. Sixty-six percent were in private practice. Eighty-nine percent used a computerized billing system. Thirty-two percent used an EMR system. Use of an EMR system was more likely for those in academic practices (p = .01029, chi square) but was not statistically influenced by age, size of the practice group, or the number of offices or hospitals used in the practice. The opinions expressed were exceptionally varied. The most common potential benefit of an EMR system cited was the ease of chart handling and accessibility. The most common perceived barriers to successful EMR implementation were cost (50%) and training of staff and physicians (30%). CONCLUSIONS: The survey highlighted the widely divergent opinions regarding the potential benefits (cost savings and improved quality of medical record) and barriers to implantations (e.g. issues dealing with mixed electronic and paper charts and managing the transition to an EMR system). The wide variety of opinions is partly a consequence of the lack of easily accessible information about office-based EMR systems and how to choose among the many vendors. A brief overview of the essential elements to be considered before acquiring an EMR system is included.

Prognostic factors for survival of 194 patients with low infiltrate leukemia.

Prognostic factors were identified from the histories of 194 patients diagnosed as having low infiltrate leukemia (LIL) between 1973 and 1981, when the policy was to delay treatment until there was evidence of progressive disease or life-threatening morbidity. Their median age was 59 yr; 63% were male; 30 had had a malignant disease previously. Presenting symptoms included anemia, 82%; infections, 15%; and hemorrhage, 16%. The group's median survival was 42 weeks, with high marrow cellularity and percentage of blasts, impairment of bone marrow, liver or renal function, age over 65 yr and performance status less than 80% associated with poorer survival. Cytogenetic changes associated with poor survival included loss of chromosome 5 or 7, additional chromosome 8, karyotypic instability, and presence of 100% abnormal metaphases. A regression model including terms for blood and bone marrow features, and age at hospital admission was able to stratify patients into prognostic groups in the same population and in an independent population admitted prior to 1973. Further prospective testing of the model is required. Twenty-six of the 78 patients who were eventually treated with combination chemotherapy achieved complete remission. The presence of Auer rods, diagnosis of acute leukemia or refractory anemia with excess blasts, rapid increase in marrow infiltrate and favorable cytogenetic karyotype were associated with response. Delaying treatment in all patients was found to have improved only modestly the survival of patients with LIL.

Emission pattern of high-energy pions: A new probe for the early phase of heavy-Ion collisions

The emission pattern of charged pions has been measured in Au+Au collisions at 1 GeV/nucleon incident energy. In peripheral collisions and at target rapidities, high-energy pions are emitted preferentially towards the target spectator matter. In contrast, low-energy pions are emitted predominantly in the opposite direction. The corresponding azimuthal anisotropy is explained by the interaction of pions with projectile and target spectator matter. This interaction with the spectator matter causes an effective shadowing which varies with time during the reaction. Our observations show that high-energy pions stem from the early stage of the collision whereas low-energy pions freeze out later.

Evidence for a Soft Nuclear Equation-of-State from Kaon Production in Heavy-Ion Collisions.

The production of pions and kaons has been measured in 197Au+197Au collisions at beam energies from 0.6 to 1.5A GeV with the kaon spectrometer at SIS/GSI. The K+ meson multiplicity per nucleon is enhanced in Au+Au collisions by factors up to 6 relative to C+C reactions, whereas the corresponding pion ratio is reduced. The ratio of the K+ meson excitation functions for Au+Au and C+C collisions increases with decreasing beam energy. This behavior is expected for a soft nuclear equation-of-state.

Comparison of polysaccharide iron complexes used as iron supplements.

An oral hematinic marketed as "water soluble polysaccharide iron complex" (Vitaline Formulas) has been characterized using x-ray powder diffraction and Mössbauer spectroscopy. Another polysaccharide iron complex marketed as Niferex (Central Pharmaceuticals) has been previously studied by us and found to have a core similar to ferrihydrite, but with some long-range order of the mineral akaganéite, beta-FeOOH. The latter is seen in other ferric carbohydrate complexes synthesized by the hydrolysis of FeCl3. This commercial product, however, is very different and has a mixture of iron components including hematite (alpha-Fe2O3) magnetite (Fe3O4), goethite (alpha-FeOOH), iron metal, and a ferrous salt.

The recharacterization of a polysaccharide iron complex (Niferex).

An oral hematinic marketed as "Niferex," the active component of which is a polysaccharide-iron complex (PIC), has recently been recharacterized. PIC is synthesized by the neutralization of an FeCl3 carbohydrate solution. Original characterization of this complex by Mössbauer spectroscopy and X-ray powder diffraction suggested that the iron-rich core was similar in structure to the mineral ferrihydrite. Higher precision X-ray powder diffraction now indicates that the core has a long-range order more similar to the mineral akaganéite, beta-FeOOH, than to ferrihydrite. This structure has been found for other similar ferric iron-carbohydrate polymers, especially those synthesized by the hydrolysis of FeCl3. Also discussed are the variable temperature (24-295 K) Mössbauer spectroscopic data for PIC. The first example of EXAFS data for polysaccharide iron complexes confirms that the iron is in an octahedral environment, coordinated to oxygen, with a short-range order similar to that for ferritin. The second iron shells in the PIC samples are less ordered than the second shell in ferritin. The size of the PIC core was found to be approximately 5 nm by X-ray powder diffraction, and is of the same order of magnitude as the ferritin core.

Dedicated minimally invasive surgery suites increase operating room efficiency.

BACKGROUND: The rapid adoption of laparoscopic surgery since the late 1980s added tremendous complexity into the operating room (OR) environment. For each case, a plethora of additional equipment-including monitors, video equipment, wiring, tubing, and cords-had to be set up, prolonging OR turnover time and decreasing OR efficiency. In 1993, the concept of designated minimally invasive surgery (MIS) suites was introduced. MIS suites integrated monitors and video equipment into the OR on ceiling-mounted columns and moved the controls to a centralized nursing station. The overall effect of this innovation on OR efficiency has not been measured. METHODS: Five RNs with varying degrees of MIS experience were instructed on video setup and put-away criteria and then timed while performing a set of standardized tasks. Each set of tasks was performed twice using a standardized surgery model. Differences in setup and put-away times between MIS suites and standard ORs were tested using the t-test for paired comparisons. RESULTS: The mean +/- standard deviation (SD) video setup times were 27.9 +/- 5.3 sec (MIS) and 254.3 +/- 54.0 sec (standard); the put-away times were 19.8 +/- 2.7 sec (MIS) and 222.3 +/- 26.0 sec (standard). The mean difference +/- standard error (SE) in both the setup (226.4 +/- 16.9 sec, p = 0.0001) and put-away times (202.5 +/- 8.6, p = 0.0001) were large and statistically significant. CONCLUSION: Using a simulation model, we have demonstrated that the use of a MIS suite reduces video setup and put-away time significantly, with the potential for significant associated cost savings. This provides just one justification for the high cost of building such "ORs of the future."

[Cochlear implants]. / A cochlearis implantáció.

Cochlear implantation is a method of utmost importance recently employed in ear surgery. It makes even speech understanding possible with electrical stimulation of the inner ear in case of bilateral total deafness of cochlear origin. The authors have performed cochlear implantation for 10 years at the Ear-Nose and Throat Clinic of Semmelweis University. Since 1985 different implantation techniques have been used in case of 58 patients, both adults and children. The authors give account of of technical details, rapidly changing selection criteria and the call attention to the problems of peri- and postoperative period and rehabilitation, on they basis of their own results. Importance of team-work of the ear-surgeon, audiologist, psychologist, physicist and speech-therapist is emphasized, because success of the operation is based on proper selection, skillful operating techniques and postoperative rehabilitation, as well.