International cooperation in endourology: percutaneous and flexible ureteroscopic treatment of lower pole kidney stones

Introduction Lower pole kidney stones represent at time a challenge for the urologist. The gold standard treatment for intrarenal stones <2 cm is Extracorporeal Shock Wave Lithotripsy (ESWL) while for those >2 cm is Percutaneous Nephrolithotomy (PCNL). The success rate of ESWL, however, decreases when it is employed for lower pole stones, and this is particularly true in the presence of narrow calices or acute infundibular angles. Studies have proved that ureteroscopy (URS) is an efficacious alternative to ESWL for lower pole stones <2 cm, but this is not reflected by either the European or the American guidelines. The aim of this study is to present the results of a large series of flexible ureteroscopies and PCNLs for lower pole kidney stones from high-volume centers, in order to provide more evidences on the potential indications of the flexible ureteroscopy for the treatment of kidney stones. Materials and Methods A database was created and the participating centres retrospectively entered their data relating to the percutaneous and flexible ureteroscopic management of lower pole kidney stones. Patients included were treated between January 2005 and January 2010. Variables analyzed included case load number, preoperative and postoperative imaging, stone burden, anaesthesia (general vs. spinal), type of lithotripter, access location and size, access dilation type, ureteral access sheath use, visual clarity, operative time, stone-free rate, complication rate, hospital stay, analgesic requirement and follow-up time. Stone-free rate was defined as absence of residual fragments or presence of a single fragment <2 mm in size at follow-up imaging. Primary end-point was to test the efficacy and safety of flexible URS for the treatment of lower pole stones; the same descriptive analysis was conducted for the PCNL approach, as considered the gold standard for the treatment of lower pole kidney stones. In this setting, no statistical analysis was conducted owing to the different selection criteria of the patients. Secondary end-point consisted in matching the results of stone-free rates, operative time and complications rate of flexible URS and PCNL in the subgroup of patients harbouring lower pole kidney stones between 1 and 2 cm in the higher diameter. Results A total 246 patients met the criteria for inclusion. There were 117 PCNLs (group 1) and 129 flexible URS (group 2). Ninety-six percent of cases were diagnosed by CT KUB scan. Mean stone burden was 175±160 and 50±62 mm2 for groups 1 and 2, respectively. General anaesthesia was induced in 100 % and 80% of groups 1 and 2, respectively. Pneumo-ultrasonic energy was used in 84% of cases in the PCNL group, and holmium laser in 95% of the cases in the flexible URS group. The mean operative time was 76.9±44 and 63±37 minutes for groups 1 and 2 respectively. There were 12 major complications (11%) in group 1 (mainly Grade II complications according to Clavidien classification) and no major complications in group 2. Mean hospital stay was 5.7 and 2.6 days for groups 1 and 2, respectively. Ninety-five percent of group 1 and 52% of group 2 required analgesia for a period longer than 24 hours. Intraoperative stone-free rate after a single treatment was 88.9% for group 1 and 79.1% for group 2. Overall, 6% of group 1 and 14.7% of group 2 required a second look procedure. At 3 months, stone-free rates were 90.6% and 92.2% for groups 1 and 2, respectively, as documented by follow-up CT KUB (22%) or combination of intra-venous pyelogram, regular KUB and/or kidney ultrasound (78%). In the subanalysis conducted comparing 82 vs 65 patients who underwent PCNL and flexible URS for lower pole stones between 1 and 2 cm, intreoperative stone-free rates were 88% vs 68% (p= 0.03), respectively; anyway, after an auxiliary procedure which was necessary in 6% of the cases in group 1 and 23% in group 2 (p=0.03), stone-free rates at 3 months were not statistically significant (91.5% vs 89.2%; p=0.6). Conversely, the patients undergoing PCNL maintained a higher risk of complications during the procedure, with 9 cases observed in this group versus 0 in the group of patients treated with URS (p=0.01) Conclusions These data highlight the value of flexible URS as a very effective and safe option for the treatment of kidney stones; thanks to the latest generation of flexible devices, this new technical approach seems to be a valid alternative in particular for the treatment of lower pole kidney stones less than 2 cm. In high-volume centres and in the hands of skilled surgeons, this technique can approach the stone-free rates achievable through PCNL in lower pole stones between 1 and 2 cm, with a very low risk of complications. Furthermore, the results confirm the high success rate and relatively low morbidity of modern PCNL for lower pole stones, with no difference detectable between the prone and supine position.

Partial melting within the lower crust – Constraints from bulk rock geochemical data and trace element mineral analyses of granulites and migmatites from Central Finland

This PhD thesis concerns geochemical constraints on recycling and partial melting of Archean continental crust. A natural example of such processes was found in the Iisalmi area of Central Finland. The rocks from this area are Middle to Late Archean in age and experienced metamorphism and partial melting between 2.7-2.63 Ga. The work is based on extensive field work. It is furthermore founded on bulk rock geochemical data as well as in-situ analyses of minerals. All geochemical data were obtained at the Institute of Geosciences, University of Mainz using X-ray fluorescence, solution ICP-MS and laser ablation-ICP-MS for bulk rock geochemical analyses. Mineral analyses were accomplished by electron microprobe and laser ablation ICP-MS. Fluid inclusions were studied by microscope on a heating-freezing-stage at the Geoscience Center, University Göttingen. Part I focuses on the development of a new analytical method for bulk rock trace element determination by laser ablation-ICP-MS using homogeneous glasses fused from rock powder on an Iridium strip heater. This method is applicable for mafic rock samples whose melts have low viscosities and homogenize quickly at temperatures of ~1200°C. Highly viscous melts of felsic samples prevent melting and homogenization at comparable temperatures. Fusion of felsic samples can be enabled by addition of MgO to the rock powder and adjustment of melting temperature and melting duration to the rock composition. Advantages of the fusion method are low detection limits compared to XRF analyses and avoidance of wet-chemical processing and use of strong acids as in solution ICP-MS as well as smaller sample volumes compared to the other methods. Part II of the thesis uses bulk rock geochemical data and results from fluid inclusion studies for discrimination of melting processes observed in different rock types. Fluid inclusion studies demonstrate a major change in fluid composition from CO2-dominated fluids in granulites to aqueous fluids in TTG gneisses and amphibolites. Partial melts were generated in the dry, CO2-rich environment by dehydration melting reactions of amphibole which in addition to tonalitic melts produced the anhydrous mineral assemblages of granulites (grt + cpx + pl ± amph or opx + cpx + pl + amph). Trace element modeling showed that mafic granulites are residues of 10-30 % melt extraction from amphibolitic precursor rocks. The maximum degree of melting in intermediate granulites was ~10 % as inferred from modal abundances of amphibole, clinopyroxene and orthopyroxene. Carbonic inclusions are absent in upper-amphibolite facies migmatites whereas aqueous inclusion with up to 20 wt% NaCl are abundant. This suggests that melting within TTG gneisses and amphibolites took place in the presence of an aqueous fluid phase that enabled melting at the wet solidus at temperatures of 700-750°C. The strong disruption of pre-metamorphic structures in some outcrops suggests that the maximum amount of melt in TTG gneisses was ~25 vol%. The presence of leucosomes in all rock types is taken as the principle evidence for melt formation. However, mineralogical appearance as well as major and trace element composition of many leucosomes imply that leucosomes seldom represent frozen in-situ melts. They are better considered as remnants of the melt channel network, e.g. ways on which melts escaped from the system. Part III of the thesis describes how analyses of minerals from a specific rock type (granulite) can be used to determine partition coefficients between different minerals and between minerals and melt suitable for lower crustal conditions. The trace element analyses by laser ablation-ICP-MS show coherent distribution among the principal mineral phases independent of rock composition. REE contents in amphibole are about 3 times higher than REE contents in clinopyroxene from the same sample. This consistency has to be taken into consideration in models of lower crustal melting where amphibole is replaced by clinopyroxene in the course of melting. A lack of equilibrium is observed between matrix clinopyroxene / amphibole and garnet porphyroblasts which suggests a late stage growth of garnet and slow diffusion and equilibration of the REE during metamorphism. The data provide a first set of distribution coefficients of the transition metals (Sc, V, Cr, Ni) in the lower crust. In addition, analyses of ilmenite and apatite demonstrate the strong influence of accessory phases on trace element distribution. Apatite contains high amounts of REE and Sr while ilmenite incorporates about 20-30 times higher amounts of Nb and Ta than amphibole. Furthermore, trace element mineral analyses provide evidence for magmatic processes such as melt depletion, melt segregation, accumulation and fractionation as well as metasomatism having operated in this high-grade anatectic area.

Subject-specific musculoskeletal models of the lower limbs for the prediction of skeletal loads during motion

The determination of skeletal loading conditions in vivo and their relationship to the health of bone tissues, remain an open question. Computational modeling of the musculoskeletal system is the only practicable method providing a valuable approach to muscle and joint loading analyses, although crucial shortcomings limit the translation process of computational methods into the orthopedic and neurological practice. A growing attention focused on subject-specific modeling, particularly when pathological musculoskeletal conditions need to be studied. Nevertheless, subject-specific data cannot be always collected in the research and clinical practice, and there is a lack of efficient methods and frameworks for building models and incorporating them in simulations of motion. The overall aim of the present PhD thesis was to introduce improvements to the state-of-the-art musculoskeletal modeling for the prediction of physiological muscle and joint loads during motion. A threefold goal was articulated as follows: (i) develop state-of-the art subject-specific models and analyze skeletal load predictions; (ii) analyze the sensitivity of model predictions to relevant musculotendon model parameters and kinematic uncertainties; (iii) design an efficient software framework simplifying the effort-intensive phases of subject-specific modeling pre-processing. The first goal underlined the relevance of subject-specific musculoskeletal modeling to determine physiological skeletal loads during gait, corroborating the choice of full subject-specific modeling for the analyses of pathological conditions. The second goal characterized the sensitivity of skeletal load predictions to major musculotendon parameters and kinematic uncertainties, and robust probabilistic methods were applied for methodological and clinical purposes. The last goal created an efficient software framework for subject-specific modeling and simulation, which is practical, user friendly and effort effective. Future research development aims at the implementation of more accurate models describing lower-limb joint mechanics and musculotendon paths, and the assessment of an overall scenario of the crucial model parameters affecting the skeletal load predictions through probabilistic modeling.

"Influence of lower-limb joint models on subject-specific musculoskeletal model predictions during gait" ( "modelli muscoloscheletrici personalizzati dell'arto inferiore: Analisi dell'effetto della modellazione dei giunti sulla predizione dei carichi agenti sul sistema scheletrico durante il cammino").

The aim of the present thesis was to investigate the influence of lower-limb joint models on musculoskeletal model predictions during gait. We started our analysis by using a baseline model, i.e., the state-of-the-art lower-limb model (spherical joint at the hip and hinge joints at the knee and ankle) created from MRI of a healthy subject in the Medical Technology Laboratory of the Rizzoli Orthopaedic Institute. We varied the models of knee and ankle joints, including: knee- and ankle joints with mean instantaneous axis of rotation, universal joint at the ankle, scaled-generic-derived planar knee, subject-specific planar knee model, subject-specific planar ankle model, spherical knee, spherical ankle. The joint model combinations corresponding to 10 musculoskeletal models were implemented into a typical inverse dynamics problem, including inverse kinematics, inverse dynamics, static optimization and joint reaction analysis algorithms solved using the OpenSim software to calculate joint angles, joint moments, muscle forces and activations, joint reaction forces during 5 walking trials. The predicted muscle activations were qualitatively compared to experimental EMG, to evaluate the accuracy of model predictions. Planar joint at the knee, universal joint at the ankle and spherical joints at the knee and at the ankle produced appreciable variations in model predictions during gait trials. The planar knee joint model reduced the discrepancy between the predicted activation of the Rectus Femoris and the EMG (with respect to the baseline model), and the reduced peak knee reaction force was considered more accurate. The use of the universal joint, with the introduction of the subtalar joint, worsened the muscle activation agreement with the EMG, and increased ankle and knee reaction forces were predicted. The spherical joints, in particular at the knee, worsened the muscle activation agreement with the EMG. A substantial increase of joint reaction forces at all joints was predicted despite of the good agreement in joint kinematics with those of the baseline model. The introduction of the universal joint had a negative effect on the model predictions. The cause of this discrepancy is likely to be found in the definition of the subtalar joint and thus, in the particular subject’s anthropometry, used to create the model and define the joint pose. We concluded that the implementation of complex joint models do not have marked effects on the joint reaction forces during gait. Computed results were similar in magnitude and in pattern to those reported in literature. Nonetheless, the introduction of planar joint model at the knee had positive effect upon the predictions, while the use of spherical joint at the knee and/or at the ankle is absolutely unadvisable, because it predicted unrealistic joint reaction forces.

Aircraft-based in-situ aerosol mass spectrometry: Chemical characterization and source identification of submicron particulate matter in the free and upper troposphere and lower stratosphere

The composition of the atmosphere is frequently perturbed by the emission of gaseous and particulate matter from natural as well as anthropogenic sources. While the impact of trace gases on the radiative forcing of the climate is relatively well understood the role of aerosol is far more uncertain. Therefore, the study of the vertical distribution of particulate matter in the atmosphere and its chemical composition contribute valuable information to bridge this gap of knowledge. The chemical composition of aerosol reveals information on properties such as radiative behavior and hygroscopicity and therefore cloud condensation or ice nucleus potential. rnThis thesis focuses on aerosol pollution plumes observed in 2008 during the POLARCAT (Polar Study using Aircraft, Remote Sensing, Surface Measurements and Models, of Climate, Chemistry, Aerosols, and Transport) campaign over Greenland in June/July and CONCERT (Contrail and Cirrus Experiment) campaign over Central and Western Europe in October/November. Measurements were performed with an Aerodyne compact time-of-flight aerosol mass spectrometer (AMS) capable of online size-resolved chemical characterization of non-refractory submicron particles. In addition, the origins of pollution plumes were determined by means of modeling tools. The characterized pollution episodes originated from a large variety of sources and were encountered at distinct altitudes. They included pure natural emissions from two volcanic eruptions in 2008. By the time of detection over Western Europe between 10 and 12 km altitude the plume was about 3 months old and composed to 71 % of particulate sulfate and 21 % of carbonaceous compounds. Also, biomass burning (BB) plumes were observed over Greenland between 4 and 7 km altitude (free troposphere) originating from Canada and East Siberia. The long-range transport took roughly one and two weeks, respectively. The aerosol was composed of 78 % organic matter and 22 % particulate sulfate. Some Canadian and all Siberian BB plumes were mixed with anthropogenic emissions from fossil fuel combustion (FF) in North America and East Asia. It was found that the contribution of particulate sulfate increased with growing influences from anthropogenic activity and Asia reaching up to 37 % after more than two weeks of transport time. The most exclusively anthropogenic emission source probed in the upper troposphere was engine exhaust from commercial aircraft liners over Germany. However, in-situ characterization of this aerosol type during aircraft chasing was not possible. All long-range transport aerosol was found to have an O:C ratio close to or greater than 1 implying that low-volatility oxygenated organic aerosol was present in each case despite the variety of origins and the large range in age from 3 to 100 days. This leads to the conclusion that organic particulate matter reaches a final and uniform state of oxygenation after at least 3 days in the free troposphere. rnExcept for aircraft exhaust all emission sources mentioned above are surface-bound and thus rely on different types of vertical transport mechanisms, such as direct high altitude injection in the case of a volcanic eruption, or severe BB, or uplift by convection, to reach higher altitudes where particles can travel long distances before removal mainly caused by cloud scavenging. A lifetime for North American mixed BB and FF aerosol of 7 to 11 days was derived. This in consequence means that emission from surface point sources, e.g. volcanoes, or regions, e.g. East Asia, do not only have a relevant impact on the immediate surroundings but rather on a hemispheric scale including such climate sensitive zones as the tropopause or the Arctic.

Surgical treatment of upper, middle and lower cervical injuries and non-unions by anterior procedures

The goals of any treatment of cervical spine injuries are: return to maximum functional ability, minimum of residual pain, decrease of any neurological deficit, minimum of residual deformity and prevention of further disability. The advantages of surgical treatment are the ability to reach optimal reduction, immediate stability, direct decompression of the cord and the exiting roots, the need for only minimum external fixation, the possibility for early mobilisation and clearly decreased nursing problems. There are some reasons why those goals can be reached better by anterior surgery. Usually the bony compression of the cord and roots comes from the front therefore anterior decompression is usually the procedure of choice. Also, the anterior stabilisation with a plate is usually simpler than a posterior instrumentation. It needs to be stressed that closed reduction by traction can align the fractured spine and indirectly decompress the neural structures in about 70%. The necessary weight is 2.5 kg per level of injury. In the upper cervical spine, the odontoid fracture type 2 is an indication for anterior surgery by direct screw fixation. Joint C1/C2 dislocations or fractures or certain odontoid fractures can be treated with a fusion of the C1/C2 joint by anterior transarticular screw fixation. In the lower and middle cervical spine, anterior plating combined with iliac crest or fibular strut graft is the procedure of choice, however, a solid graft can also be replaced by filled solid or expandable vertebral cages. The complication of this surgery is low, when properly executed and anterior surgery may only be contra-indicated in case of a significant lesion or locked joints.

Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis

OBJECTIVE: Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). METHODS: A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). RESULTS: In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). CONCLUSION: Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

Renal insufficiency is independently associated with a distal distribution pattern of symptomatic lower-limb atherosclerosis

Objectives The purpose of this study was to assess the impact of renal insufficiency (RI) on the distribution pattern of peripheral arterial disease (PAD). We hypothesised that RI is associated with a distally accentuated involvement of the peripheral arterial tree. Design This is a retrospective analysis. Materials and Methods Analysis was based on a consecutive series of 2709 patients with chronic PAD of atherosclerotic origin undergoing primary endovascular treatment of lower-extremity arteries. Atherosclerotic pattern was grouped into femoropopliteal (n = 2085) and infragenicular (n = 892) disease according to target lesions treated while using iliac disease (n = 1133) as reference. Univariable and multivariable multinomial regression analyses were performed to assess relation with RI. Results are shown as relative risk ratio (RRRs) with 95% confidence intervals (95% CIs). A p < 0.05 was considered statistically significant. RI was defined as glomerular filtration rate (GFR) < 60 ml min−1 1.73 m−2. Results Presence of RI was an independent risk factor for a centrifugal lesion pattern (RRR 1.48, 95% CI: 1.17–1.86, p = 0.001). Moreover, a decrease in GFR by 10 ml min−1 1.73 m−2 was associated with an RRR of 1.08 for below-the-knee arterial disease (95% CI: 1.03–1.13, p = 0.003). Conclusion Presence and severity of RI are independent predictors of a distal obstructive pattern in patients with symptomatic PAD.

Impact of obesity on venous hemodynamics of the lower limbs

Obesity is a risk factor for chronic venous insufficiency and venous thromboembolism. The aim of this study was to compare venous flow parameters of the lower limbs assessed by duplex ultrasound scanning in obese and nonobese individuals according to body mass index (BMI).

[Right-sided lower abdominal pain and diarrhea of a young diabetic woman]

We report the case of a 24-years old diabetic women hospitalised because of right-sided lower abdominal pain and diarrhea. She fulminantly developed shock before appendectomy could be performed and was transferred to intensive care unit. Hypotension remained and laparoscopy revealed primary peritonitis and toxic shock syndrome by Group A Streptococcus which was cultivated in blood and ascites. Therapy with penicilline and clindamycine resolved symptoms. During hospitalisation Clostridium difficile colitis occurred. This complication leaded to prolonged hospitalisation.

Effects of thoracic epidural analgesia on lower urinary tract function in women

The need for an indwelling transurethral catheter in patients with postoperative thoracic epidural analgesia (TEA) is a matter of controversy. Subjective observations are ambivalent and the literature addressing this issue is scarce. As segmental blockade can be achieved with epidural analgesia, we hypothesized that analgesia within segments T4-T11 has no or minimal influence on lower urinary tract function. Thus, we evaluated the effect of TEA on lower urinary tract function by urodynamic studies.

Fatal lower extremity varicose vein rupture

Varicose vein rupture is a rare cause of death, although varicosities are a common pathology. We present three cases of sudden death due to varicose vein rupture. After a review of the literature, the case circumstances and the findings of imaging examination, performed in two cases, are presented. One of them had undergone a post-mortem computed tomography angiography (PMCTA), and one a PMCTA as well as a post-mortem magnetic resonance (PMMR) imaging prior to conventional autopsy. One of the cases presented herein is, to our knowledge, the youngest known fatality due to varicose vein rupture.

The Influence of Abdominal Pressure on Lower Extremity Venous Pressure and Hemodynamics: A Human In-vivo Model Simulating the Effect of Abdominal Obesity

To demonstrate that abdominal pressure impacts venous flow and pressure characteristics.

Sacral neuromodulation for neurogenic lower urinary tract dysfunction: systematic review and meta-analysis

Context Treatment of neurogenic lower urinary tract dysfunction (LUTD) is a challenge, because conventional therapies often fail. Sacral neuromodulation (SNM) has become a well-established therapy for refractory non-neurogenic LUTD, but its value in patients with a neurologic cause is unclear. Objective To assess the efficacy and safety of SNM for neurogenic LUTD. Evidence acquisition Studies were identified by electronic search of PubMed, EMBASE, and ScienceDirect (on 15 April 2010) and hand search of reference lists and review articles. SNM articles were included if they reported on efficacy and/or safety of tested and/or permanently implanted patients suffering from neurogenic LUTD. Two reviewers independently selected studies and extracted data. Study estimates were pooled using Bayesian random-effects meta-analysis. Evidence synthesis Of the 26 independent studies (357 patients) included, the evidence level ranged from 2b to 4 according to the Oxford Centre for Evidence-Based Medicine. Half (n = 13) of the included studies reported data on both test phase and permanent SNM; the remaining studies were confined to test phase (n = 4) or permanent SNM (n = 9). The pooled success rate was 68% for the test phase (95% credibility interval [CrI], 50–87) and 92% (95% CrI, 81–98%) for permanent SNM, with a mean follow-up of 26 mo. The pooled adverse event rate was 0% (95% CrI, 0–2%) for the test phase and 24% (95% CrI, 6–48%) for permanent SNM. Conclusions There is evidence indicating that SNM may be effective and safe for the treatment of patients with neurogenic LUTD. However, the number of investigated patients is low with high between-study heterogeneity, and there is a lack of randomised, controlled trials. Thus, well-designed, adequately powered studies are urgently needed before more widespread use of SNM for neurogenic LUTD can be recommended.