Beyond the marrow: insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors.

Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.

Antimicrobial susceptibility of bacterial isolates from patients presenting with ear, nose and throat (ENT) infections in the German community healthcare setting.

Empiric initial antibiotic therapy of bacterial infections is based primarily upon the susceptibility of the most common causative pathogens. The purpose of this study was to provide susceptibility data on six bacterial species known to cause ear, nose and throat (ENT) infections. A total of 1066 isolates collected during a nationwide laboratory-based surveillance study were analysed. All Streptococcus pyogenes isolates were penicillin (PEN)-susceptible, indicating that natural penicillins can still be recommended as the first-line treatment for group A streptococcal tonsillopharyngitis. Of the S. pneumoniae isolates, 92.9% were PEN-susceptible and of the Haemophilus influenzae isolates, 89.7% were amoxicillin-susceptible, retaining aminopenicillins as the first-line treatment for acute otitis media (AOM) and acute rhinosinusitis (ARS), in case antibiotic therapy is considered. In contrast, cefuroxime axetil seems less likely to be suitable for the treatment of AOM or ARS, as all Moraxella catarrhalis and >99% of the H. influenzae isolates were categorised as intermediate or resistant. The susceptibility rates of Pseudomonas aeruginosa were 97-100% for the drugs tested, except for the fluoroquinolones (87.6%). Overall, bacterial isolates from outpatients presenting with ENT infections showed low frequencies of resistance in Germany. However, given the emergence of multidrug resistance to standard antibiotics in Escherichia coli and other pathogens, inappropriate use of broad-spectrum antibiotics for the treatment of ENT infections has to be avoided.

Effects of functional endoscopic sinus surgery on the acoustics of the sinonasal tract.

BACKGROUND: Nasal and paranasal cavities are supposed to contribute substantially to the vocal tract resonator properties. However, their acoustical effects as well as the effects of sinus surgery on the voice remain unclear. In this work we investigate resonance phenomena of paranasal sinuses prior to and after various rhinosurgical procedures in cadaveric human sinonasal tracts and corresponding 3D casts. METHODOLOGY: Nasal and paranasal cavities of formalin-preserved cadavers and corresponding 3D replicas were excited by sine-tone sweeps from an earphone placed in the epipharynx. The response was picked up by a microphone at the nostrils. Different FESS procedures were performed and the acoustical responses following excitation were recorded. The measured acoustical changes in the obtained transfer functions were then evaluated. RESULTS: Marked low frequency dips were detected in the transfer functions when sinus cavities were included in the nasal resonator system. These dips showed a significant correlation with sinus volumes. Following FESS procedures they moved upwards in frequency depending on the extent of the surgical intervention. CONCLUSIONS: The transfer functions obtained in cadaveric situs and 3D replicas showed dips at the resonance frequencies of the paranasal cavities. Marked acoustic effects in terms of increase in dip frequency following FESS procedures were reproducibly documented.

Resonator properties of paranasal sinuses: preliminary results of an anatomical study.

BACKGROUND: The contribution of the nasal and paranasal cavities to vocal tract resonator properties is unclear as are voice effects of sinus surgery. Here we investigate resonance phenomena of paranasal sinuses with and without selective occlusion of the middle meatus and maxillary ostium in a cadaver. METHODOLOGY: Nasal and paranasal cavities of a Thiel-embalmed cadaver were excited by sine-tone sweeps from an earphone in the epipharynx. The response was picked up by a microphone at the nostrils. Different conditions with blocked and unblocked middle meatus were tested. Additionally, infundibulotomy was performed allowing direct access to and selective occlusion of the maxillary ostium. RESULTS: Responses showed high reproducibility. Minor effects appeared after removal of meatal occlusion. A marked low frequency dip was detected after removal of occlusion of maxillary ostium following infundibulotomy. CONCLUSION: Reproducible frequency responses of nasal tract can be derived from cadaver measurements. Marked acoustic effects of the maxillary sinus appeared only after direct exposure of the maxillary ostium following infundibulotomy.

Patient comfort following FESS and Nasopore® packing, a double blind, prospective, randomized trial.

BACKGROUND: The use of nasal packing after functional endoscopic sinus surgery (FESS) is often associated with pain and a feeling of pressure for patients. The aim of the present work was to investigate a modern wound dressing made of polyurethane (Nasopore®) that makes removal of the nasal packing unnecessary and is focussed on patient comfort. METHODOLOGY: Following bilateral FESS, after randomisation, one side was packed with Nasopore® while the other side was without packing as a control. The following parameters from 47 patients were determined daily in two centres from post-operative day 1 for the duration of the inpatient stay in a double-blinded setting: side-specific post-operative bleeding, nasal breathing and feeling of pressure as well as the general parameters sleep disturbance, headaches and general well-being. Which side patients considered subjectively the better was also recorded. RESULTS: No significant differences were determined between the two sides in terms of the rates of post-operative bleeding and nasal breathing. The feeling of pressure was slightly less on the side packed with Nasopore® on post-operative days 2 and 3. No trend could be observed regarding which side patients described as being subjectively better. CONCLUSION: There were only slight differences in patient comfort between the Nasopore® side and the control. Because the feeling of pressure in the midface was significantly less and there were no complications, this suggests there is greater patient comfort when using Nasopore® compared to using no nasal packing.

Endoscopic sinus surgery training courses: benefit and problems - a multicentre evaluation to systematically improve surgical training.

BACKGROUND: The aim of this multicentre study was to systematically analyse the strengths and weaknesses in the surgical training for endoscopic sinus surgery (ESS) and identify measures that may improve training. METHODOLOGY: Using a structured questionnaire, 133 participants of ESS courses in seven centres in Germany, Switzerland and Australia were asked about their experiences during their dissection courses and how they perceived their course could be improved. RESULTS: Gaining confidence in handling of instruments and endoscopes was only a problem for participants with little experience in ESS. The majority of the participants, independent from their level of training, considered infundibulotomy and anterior ethmoidectomy as the easiest dissection steps, whilst surgery of the frontal sinus posed a considerable challenge for many surgeons even those with a higher level of training. Participants with and without ESS experience thought that emphasis on anatomy was the most important improvement that could be made during their surgical training. Virtually all participants stated that the course improved their anatomical knowledge, their surgical skills and their confidence when performing ESS. CONCLUSIONS: ESS dissection courses are considered beneficial by surgical trainees. Participants felt that more emphasis on sinus anatomy in conjunction with private study is essential to maximize their skills in surgical dissection. For beginners with ESS, an infundibulotomy and anterior ethmoidectomy were thought to be the best initial procedures to help develop endoscopic surgical skills.

[Symptoms and treatment of choanal atresia--stenting remains controversial]. / Symptome und Therapie der Choanalatresie--Stents weiterhin umstritten.

Congenital choanal atresia is a rare malformation of the upper airways occurring sole or within the scope of syndromes. The controversy regarding standardized surgical approach and optimal technique preventing re-stenosis as well as the proceeding in case of a unilateral malformation persists. To address these issues, a retrospective analysis of patients presenting with choanal atresia in our department within the last 10 years was performed. 15 infants aged 3 days to 13 years (mean 42 months) who presented with unilateral (10 cases) and bilateral (5 cases) choanal atresia underwent surgical repair. 4 patients failed previous surgeries. All interventions were performed in transnasal endoscopic technique. 7 patients were intraoperatively stented for 6 weeks, 4 patients for 1 week. In 73% (11 out of 15 children) further congenital anomalies were identified. In 7 cases a re-stenosis requiring treatment occurred, predominantly in long-term stented patients. No intra- or postoperative hemorrhages or infections occurred. To provide an adequate work-up of affected patient including a screening for further congenital anomalies, a multidisciplinary approach is required. Endonasal endoscopic approach represents a safe technique for surgical repair of choanal atresia. The indication for surgical repair in case of a unilateral atresia is based on the severity of clinical symptoms. The use of stents, especially of long term, remains controversial and needs further evaluation.

A transiting giant planet with a temperature between 250 K and 430 K.

Of the over 400 known exoplanets, there are about 70 planets that transit their central star, a situation that permits the derivation of their basic parameters and facilitates investigations of their atmospheres. Some short-period planets, including the first terrestrial exoplanet (CoRoT-7b), have been discovered using a space mission designed to find smaller and more distant planets than can be seen from the ground. Here we report transit observations of CoRoT-9b, which orbits with a period of 95.274 days on a low eccentricity of 0.11 +/- 0.04 around a solar-like star. Its periastron distance of 0.36 astronomical units is by far the largest of all transiting planets, yielding a 'temperate' photospheric temperature estimated to be between 250 and 430 K. Unlike previously known transiting planets, the present size of CoRoT-9b should not have been affected by tidal heat dissipation processes. Indeed, the planet is found to be well described by standard evolution models with an inferred interior composition consistent with that of Jupiter and Saturn.

Endoscopic measurements of free-flap perfusion in the head and neck region using red-excited Indocyanine Green: preliminary results.

BACKGROUND: Free-tissue transfer has become a standard procedure for reconstructive surgery in the head and neck area. Flap failures are relatively rare (or=64% for all other examinations. CONCLUSIONS: It was possible to prove the feasibility of endoscopic ICG fluorescence angiography in patients undergoing free-flap transfer to the UADT. The method provides instant information about the perfusion state of the tissue and is easily performed without greater patient discomfort or risk of side effects. Due to the endoscopic approach, the method seems highly promising for this indication and merits further evaluation.

Phonon confinement in SiC nanocrystals: comparison of the size determination using transmission electron microscopy and Raman spectroscopy.

Silicon carbide fibers of different generation/processing routes (NLM-Nicalon and Tyranno SA3) were thermally treated to trigger the growth of nanocrystals, which were analyzed using Raman spectroscopy and transmission electron microscopy (TEM). The nanocrystals were also aged in molten sodium nitrate to investigate their reactivity. The spatial correlation model has been used to model the Raman spectra and extract accurate and statistical information on the nanocrystallites' structure and dimension. For the NLM fibers, an average size of 2.5 to 7.0 nm was calculated, which was in good agreement with TEM observations. For the Tyranno SA3 fiber, despite the heavily faulted stacking sequence, the Raman peaks remained sharp, indicating that the crystallite dimension calculated from the Raman spectra is only dependent on the actual size of the nanocrystals and is not affected by the sequence of the stacking faults.

Thoracic aortic aneurysms: treatment with endovascular self-expandable stent grafts.

BACKGROUND: This study was performed to evaluate the safety and feasibility of endovascular stent graft placement in the treatment of descending thoracic aortic aneurysms. METHODS: Between November 1996 and February 1999, endovascular stent graft repair was used in 21 patients. There were 5 women and 16 men with a mean age of 67 years (range, 41 to 87 years). An atherosclerotic aneurysm with a diameter of more than 6 cm was the indication for intervention in 19 patients (90.5%). In 2 patients (9.5%), a localized aortic dissection with a diameter of more than 6 cm was treated. In 71.4% (15 of 21) of patients, multiple stents were necessary for aneurysm exclusion. To allow safe deployment of the stent graft, preliminary subclavian-carotid artery transposition was performed in 9 patients (42.9%). Vascular access was achieved through a small incision in the abdominal aorta (n = 6), an iliac artery (n = 8), or a femoral artery (n = 7). Talent and Prograft stent grafts were used. RESULTS: Successful deployment of the endovascular stent grafts was achieved in all patients. Two patients died postoperatively (mortality rate, 9.5%), 1 of aneurysmal rupture and the other of impaired perfusion of the celiac axis. Repeat stenting was done in 3 patients because of intraoperative leakage. CONCLUSIONS: Endovascular stent graft repair is a promising and less invasive alternative to exclude the aneurysm from blood flow. This technique allows treatment of patients who are unsuitable for conventional surgical procedures. An exact definition of inclusion criteria and technical development of stent grafts should contribute to further improvements in clinical results.

Impact of retrograde cerebral perfusion on aortic arch aneurysm repair.

OBJECTIVE: Protection of the brain is a primary concern in aortic arch surgery. Retrograde cerebral perfusion is a relatively new technique used for cerebral protection during profound hypothermic circulatory arrest. This study was designed to compare, retrospectively, the outcome of 109 patients undergoing aortic arch operation with and without the use of retrograde cerebral perfusion. METHODS: Fifty-five patients had profound hypothermic circulatory arrest alone, and 54 patients had supplemental cerebral protection with retrograde cerebral perfusion. Mean age was 61 +/- 13 years and 58 +/- 14 years, respectively (mean +/- standard deviation). Twenty-two preoperative and intraoperative characteristics, including age, sex, acuity, presence of aortic dissection, and aneurysm rupture, were similar in the 2 groups (P >.05). RESULTS: Mean circulatory arrest times (in minutes) were 30 +/- 19 in the group without retrograde cerebral perfusion and 33 +/- 19 in the group with retrograde cerebral perfusion, respectively. chi(2) Analysis revealed that patients operated on with the use of retrograde cerebral perfusion had significantly lower hospital mortality (15% vs 31%; P =.04) and in-hospital permanent neurologic complications (9% vs 27%; P =.01). Retrograde cerebral perfusion failed to reduce the prevalence of temporary neurologic dysfunction (17% vs 18%; P =.9). Stepwise multiple logistic regression revealed that extracorporeal circulation time, age, and lack of retrograde cerebral perfusion were statistically significant independent risk factors for hospital mortality. The same analysis revealed that lack of retrograde cerebral perfusion was the only significant independent risk factor for permanent neurologic dysfunction. CONCLUSION: Retrograde cerebral perfusion decreased the prevalence of permanent neurologic complications and the hospital mortality in patients undergoing aortic arch operations.

Memantine for prevention of spinal cord injury in a rabbit model.

BACKGROUND: This study was conducted to investigate the effect of memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist, on the neurologic outcome of spinal cord ischemia after aortic occlusion. MATERIALS AND METHODS: New Zealand White rabbits were anesthetized and spinal cord ischemia was induced for 40 minutes by infrarenal aortic occlusion. Animals were randomly allocated to 3 groups. Group 1 (n = 8, control) received no pharmacologic intervention, group 2 (n = 8) received intra-aortic memantine infusion (20 mg/kg) after aortic crossclamping, and group 3 (n = 8) was treated with systemic memantine infusion (20 mg/kg) 45 minutes before aortic occlusion. Neurologic status was scored by the Tarlov system (in which 4 is normal and 0 is paraplegia) at 12, 24, 36, and 48 hours after the operation. Lumbar spinal root stimulation potentials and motor evoked potentials from lower limb muscles were monitored before, during, and after the operation. After the animals were killed, the spinal cords were studied histopathologically. RESULTS: All potentials disappeared shortly after aortic crossclamping. They returned earlier in both memantine-treated groups than in the placebo group. Histologic examination of spinal cords revealed a few abnormal motor neurons in memantine-treated rabbits but found extensive injury in the control group. At 12 hours the median Tarlov scores were 0 in the control group (group 1), 2 in the intra-aortic memantine group (group 2, P =.001 versus control), and 3 in the systemic group (group 3, P =.0002 versus control). At 24 hours median Tarlov scores were 0, 2.5 (P =.0002), and 4 (P =. 0002), respectively. Finally, at both 36 and 48 hours median Tarlov scores were 0, 3 (P =.0006), and 4 (P =.0002), respectively. CONCLUSION: Memantine significantly reduced neurologic injury related to spinal cord ischemia and reperfusion after aortic occlusion.

Perioperative risk factors for mortality in patients with acute type A aortic dissection.

BACKGROUND: Patients with acute type A aortic dissection are associated with a high mortality rate and postoperative complications. This study was designed to explore perioperative risk factors for death in patients with acute type A aortic dissection. METHODS AND RESULTS: One hundred nine consecutive surgical patients with acute type A aortic dissection were included in the present study. Thirty-five perioperative risk factors were used in the statistical analysis for mortality prediction. The 30-day mortality rate for all patients was 30% (33 of 109). Univariate analysis revealed 5 preoperative and intraoperative risk factors that were found to be statistically significant predictors for death: older age, renal failure, preoperative hemodynamic instability, preoperative cardiopulmonary resuscitation, and lack of retrograde cerebral perfusion (P < 0.05). Rupture of aneurysm, hypothermic circulatory arrest time, and operation date were not found to be risk factors for death. Stepwise multiple logistic regression confirmed that older age and lack of retrograde cerebral perfusion were statistically significant independent risk factors for death (P < 0.05). Four postoperative complications were found to be statistically significant prognostic indicators for death: liver failure, stroke, sepsis, and reoperation after the initial surgery (P < 0.05). CONCLUSIONS: Perioperative risk factors for death after the operation for acute type A aortic dissection were identified. This will allow physicians and surgeons to better assess the patient's risk, which will lead to better outcome.

Endovascular stent graft repair for aneurysms on the descending thoracic aorta.

BACKGROUND: The traditional treatment of aneurysms of the descending thoracic aorta includes posterolateral thoracotomy and aortic replacement with a prosthetic graft. In this study, we report our experiences and results in endovascular stent graft placement as an alternative to surgical repair. METHODS: Between January 1989 and July 1997, a total of 68 patients (24 women) underwent replacement of the thoracic aorta. Mean age at operation was 51 years. Fifty-eight patients underwent conventional surgical treatment. All of these patients were suitable candidates for endovascular stenting; however, no stent graft material was available at the time of operation. Ten patients (1 chronic dissection, 9 atherosclerotic aneurysm) received in the past 8 months the first commercially manufactured endovascular stent graft. The mean diameter of the aneurysms in this group was 7 cm (range, 6 to 8 cm). Two stent patients were operated on using only spinal cord analgesia. All stent grafts were custom designed for each of the 10 patients. RESULTS: The 30-day mortality in the conventional group was 31% versus 10% in the stent group. Mean length of intervention was 320 minutes in the conventional group versus 150 minutes in the endovascular group. Spinal cord injury occurred in 5 patients (12%) in the surgical group, whereas none of the stented patients developed any neurologic sequelae. Mean intensive care unit stay was 13 days, followed by a mean of 10 days on a ward in the first group compared to 4 days in the intensive care unit and 6 days on the ward in the stent group. One stent was required in 2 patients, two stents were required in 3 patients, and four stents were deployed in 5 patients of our series. Five patients required transposition of the left subclavian artery to achieve a sufficient neck for the proximal placement of the stent. There was complete thrombosis of the thoracic aortic aneurysm surrounding the stent graft in 8 patients (80%). Two patients required restenting as a result of leakage (20%). Stent graft placing was performed through the femoral artery in 8 patients, whereas access was only achieved through the abdominal aorta in 2 patients. CONCLUSIONS: These preliminary results demonstrate that endovascular stent graft replacement might be a promising, cheaper, and safe alternative method in selected patients with descending thoracic aneurysms.

[Selected aspects for quality assurance in family practice]. / Ausgewählte Aspekte zur Qualitätssicherung in der hausärztlichen Praxis.

All general practitioners of Dresden, the capital of Saxonia, were interviewed about problems of the quality assurance twice, 1995 and a year after. In 1995, the response rate was 60.7%, in 1996 83.8% of the first participants. The majority of the doctors are interested in the quality assurance of the medical care by family doctors including their own work. In their view, the different possibilities of the quality assurance and the various kinds of further medical training are of different importance. This estimation can depend on the age and sex of the physicians and on the kind of practice-organization.

[Spatial and temporal accessibility of primary health care by the patient--a survey in Dresden/Saxony]. / Räumliche und zeitliche Erreichbarkeit hausärztlicher Leistung durch den Patienten--Eine Befragung in Dresden/Sachsen.

The structural changes in outpatient medical care in eastern Germany took place by far-reaching winding up of the outpatient departments. At the same time, many doctors from these institutions set up a practice. These changes also concerned the medical care by family doctors. It is assumed that as a result of these partly extensive changes there are also changes in the accessibility of the family doctor by outpatients. We will describe in this paper the level attained in Dresden, capital of Saxony in 1995 and 1996, from the point of view of the inhabitants. Existing problems are shown. In this connection, random samples of inhabitants of Dresden were interviewed by postal survey with questions on this subject in 1995 and 1996.

Operations on the thoracic aorta and hypothermic circulatory arrest: is aprotinin safe?

INTRODUCTION: The safety of aprotinin, especially when used with profound hypothermic circulatory arrest, is still a matter of intense debate despite its presumed salutary effects on blood loss. Many investigators have reported toxic renal effects of high-dose aprotinin in such patients, but no prospective, randomized study has been conducted. To assess the potential detrimental effect of aprotinin on renal function and its putative reduction of blood loss, 50 patients undergoing thoracic aortic operations with the use of profound hypothermic circulatory arrest were randomly assigned to receive either low-dose aprotinin (1 x 10(6) kallikrein activation units) or placebo. METHODS: The specific renal tubular markers beta-2-microglobulin and beta-N-acetyl-D-glucosaminidase, as well as serum creatinine and blood urea nitrogen, creatinine clearance, sodium excretion, and potassium excretion, were measured to evaluate renal function preoperatively, immediately after the procedure, and 24 hours and 48 hours later. RESULTS: No statistically significant difference was found in any measured renal parameter between the two groups (analysis of variance). Renal dysfunction, defined as an elevation of serum creatinine early postoperatively (> or = 1.5 times the preoperative value), occurred in two patients who received aprotinin and in one patient in the control group. Temporary dialysis (hemodialysis or continuous venovenous hemofiltration) was needed in two patients in the aprotinin group versus one in the control group. Furthermore, patients treated with aprotinin had significantly less total postoperative blood loss (718 +/- 340 ml vs 920 +/- 387 ml, p = 0.04). The aprotinin recipients also had a significantly lower transfusion requirement (p < 0.05). CONCLUSION: This controlled trial of low-dose aprotinin in patients undergoing thoracic aortic operations using profound hypothermic circulatory arrest demonstrated no detectable deleterious effects on renal function; moreover, the use of aprotinin was associated with significantly lower need for transfusion.

Surgical treatment of aortic arch aneurysms in profound hypothermia and circulatory arrest.

BACKGROUND: This study was undertaken to define the factors that influence mortality rate and neurologic outcome after repair of the aortic arch and various portions of the thoracic aorta in patients with profound hypothermia and circulatory arrest. METHODS: Between November 1986 and January 1996, 105 patients were treated surgically for aortic disease involving the transverse aortic arch. Profound hypothermic circulatory arrest and selective brachiocephalic perfusion was used in all patients. In 19 patients retrograde cerebral perfusion was instituted during the period of circulatory arrest. Independent predictors for 30-day mortality and permanent neurologic deficits were evaluated by multiple logistic regression. RESULTS: Thirty-day mortality for the entire group was 19% (20/105); 21.2% for urgent versus 15.4% for elective cases, respectively. Statistical analysis showed that age is the most important factor that significantly influences mortality rate (p < 0.0145) and neurologic outcome (p < 0.006). Variables such as circulatory arrest time (p < 0.24), previous cardiac or aortic operations (p < 0.19), and sex (p < 0.55) failed to show any influence on mortality rate. Permanent neurologic deficits were diagnosed in 12.9% (11/85) of the patients. CONCLUSIONS: The incidence of permanent neurologic dysfunction as well as the mortality rate are predominantly related to the age of the patient. In this patient group, statistical analysis failed to show a direct correlation between duration of circulatory interruption and neurologic outcome.