[Mechanisms of action and clinical application of diuretics in intensive care medicine]. / Wirkmechanismen und klinische Anwendung von Diuretika in der Intensivmedizin.

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures.

Antibiotic treatment and prophylaxis of periprosthetic infections: Evaluation of 666 consecutive breast implant removals.

Periprosthetic infections are feared complications in esthetic and reconstructive breast surgery. The purpose of our study is to evaluate our institution's specific culture data and to identify most common organisms and suitable antibiotics for prophylaxis and first-line treatment. We evaluated all patients with a change or removal of breast implants from 01.01.2012 to 31.12.2017 retrospectively. Based on the medical records, the surgical indications were identified and specifically analyzed for signs of infection, reasons for primary and secondary surgery, and all available microbiological data of these interventions. A total of 666 implant removals or exchanges were performed in 431 patients. Microbiological smears were gathered from 291 patients (449 implants). Bacteria were cultured from 63 implants (56 patients). In six additional patients (ten implants), a periprosthetic infection was seen, without bacteria detection. Advanced capsular contracture correlated with a higher proportion of positive swabs (p<0.05). In 11.5% of smears, bacterial contamination was found despite absence of clinical signs of infection. Coagulase-negative staphylococci were the dominant pathogen in clinical inapparent infections, while Staphylococcus aureus was when there was clinical evidence of infection. All pathogens were sensitive to vancomycin. In the majority of cases, bacterial contamination was an incidental finding, which was more common in the presence of advanced capsular contracture. In our institution, cefuroxime and amoxicillin/clavulanic acid have been proven to be reasonable choices for prevention and treatment of periprosthetic infections. In the treatment of fulminant infections and for the prophylaxis during implant replacement due to advanced capsular contracture, vancomycin became our first choice.

Sorafenib paradoxically activates the RAS/RAF/ERK pathway in polyclonal human NK cells during expansion and thereby enhances effector functions in a dose- and time-dependent manner.

Natural killer (NK) cells play a major role in host immunity against leukaemia and lymphoma. However, clinical trials applying NK cells have not been as efficient as hoped for. Patients treated with rapidly accelerated fibrosarcoma (RAF) inhibitors exhibit increased tumour infiltration by immune cells, suggesting that a combination of RAF inhibitors with immunotherapy might be beneficial. As mitogen-activated protein kinases (MAPKs) such as raf-1 proto-oncogene, serine/threonine kinase (CRAF) regulate NK cell functions, we performed an in-vitro investigation on the potential of clinically relevant short-acting tyrosine kinase inhibitors (TKIs) as potential adjuvants for NK cell therapy: NK cells from healthy human blood donors were thus treated with sorafenib, sunitinib or the pan-RAF inhibitor ZM336372 during ex-vivo expansion. Functional outcomes assessed after washout of the drugs included cytokine production, degranulation, cytotoxicity, apoptosis induction and signal transduction with/without target cell contact. Paradoxically, sorafenib enhanced NK cell effector functions in a time- and dose-dependent manner by raising the steady-state activation level. Of note, this did not lead to NK cell exhaustion, but enhanced activity against target cells such as K562 or Daudis mediated via the RAS/RAF/extracellular-regulated kinase (ERK) pathway, but not via protein kinase B (AKT). Our data will pave the path to develop a rationale for the considered use of RAF inhibitors such as sorafenib for pre-activation in NK cell-based adoptive immune therapy.

Clinical tests and magnetic resonance imaging have limited diagnostic value for triangular fibrocartilaginous complex lesions.

INTRODUCTION: The diagnostic value of clinical tests and magnetic resonance (MR) imaging for the investigation of triangular fibrocartilaginous complex (TFCC) lesions is not clear due to a lack of clinical data. MATERIALS AND METHODS: We retrospectively analyzed 908 patients who underwent clinical tests and arthroscopy for suspected TFCC lesions at our institution. Further, MR imaging findings concerning the TFCC were gathered. We correlated clinical tests and MR imaging findings with those obtained during arthroscopy, and we calculated sensitivity, specificity, as well as positive and negative predictive values. RESULTS: In the whole cohort, the positive predictive values of all clinical tests were low, ranging from 0.53 to 0.55. The ulna grinding test had the highest sensitivity, but lowest specificity. Sensitivity and specificity of the ulnar fovea sign and magnetic resonance imaging were similar, ranging from 0.73 to 0.76, and from 0.41 to 0.44, respectively. To some degree, the diagnostic value seemed to depend on the Palmer class of TFCC lesion. CONCLUSIONS: According to this study, clinical tests and MR imaging findings are of very limited diagnostic value for the diagnosis of TFCC lesions.

Transverse soft tissue distraction preceding separation of complex syndactylies.

UNLABELLED: Various surgical techniques are described for separation of syndactylies leading to good results. However, the use of standard techniques is limited in complex syndactylies with extensive bony fusion and tight soft tissues. The aim of this study was to assess the outcomes of a two-stage procedure involving progressive soft tissue distraction prior to syndactyly release. Between 1996 and 2012 we treated 168 complex syndactylies with this technique. The main indications were syndactylies in Apert syndrome. The digits were distracted through an external fixator at 0.5 mm/day. Distraction of 15-25 mm was achieved. Soft tissue distraction provided additional skin, a wider nail matrix and more bone in the form of callus. Thus subsequent modelling of the fingertips was improved, especially if they were closely fused. This technique facilitates treatment of complex cases and improves aesthetic outcome. LEVEL OF EVIDENCE: Therapeutic IV.

[Primary adaptive vs. secondary wound closure in hand infections - differences and benefits]. / Primär adaptierende vs. sekundäre Wundverschlüsse bei Infektionen der Hand - Unterschiede und Vorteile.

BACKGROUND: Hand infections are common surgical emergencies. There are still controversial opinions regarding the ideal timing of wound closure after radical débridement of the infection. The aim of this retrospective study was to compare the outcome of primary adaptive and secondary wound closures after operative débridement in patients with hand infections. METHODS: We retrospectively analysed all infections of the hand treated operatively in our hospital in the years 2011 and 2012 with a follow-up of at least 6 months. We included 16 patients with primary adaptive wound closure (PWC) and 12 patients with secondary wound closure (SWC) in this study. The evaluated parameters were the need for re-operations, the length of hospital stay, the overall satisfaction with the treatment, the characteristics of the scar and the mobility of the hand. RESULTS: No patient had to be re-operated after PWC or SWC, respectively. Patients in the PWC group were kept significantly shorter as inpatients in comparison to patients in the SWC group (3.0 days vs. 5.1 days; p=0.048). Overall patient satisfaction with the treatment and the scar was comparable for both groups, as was the re-establishment of the mobility of the treated hand to preoperative levels. CONCLUSION: This study shows that wounds after radical débridement for infection of the hand can be closed primarily adaptive without disadvantages for the patient. The length of hospitalisation is significantly shorter if the wound is closed primarily adaptive, a fact that is important for patient comfort and the socio-economic system. Both, primary adaptive and secondary wound closures generally have good outcomes with possible advantages for primary adaptive wound closures concerning the characteristics of the scar.

[Return of sensitivity after digital nerve reconstruction in children: how does age affect outcome?]. / Sensibilitätsrückkehr nach kindlichen Nervenverlet-zungen der Hand - welche Rolle spielt das Patientenalter?

BACKGROUND: The regenerative capacity after nerve reconstruction in children is believed to be superior compared to that in adults. However, the available data on this topic are limited. The aim of this work is to improve the age-dependent assessment of the prognosis after surgical treatment of peripheral nerve injuries of the hand. PATIENTS AND METHODS: 44 of 147 children with complete transections of proper and common digital nerves who were treated from 2000 to 2009 and who were currently 6 years or older, could be included for follow-up (mean time, 7.5 years). In total there were 60 nerve injuries, of which 56 were directly coaptated, 4 needed grafting. Sensitivity of the fingertips was assessed using the 2-point discrimination (2PD) test and the Semmes-Weinstein monofilament test. We also recorded hypersensitivity, sensitivity to cold, and paresthesia. To account for inter-individual differences in normal 2PD, the difference of the 2PD to the uninjured contralateral side was calculated as delta-2PD. The age at the time of the injury, divided into groups of 0-5, 6-10 and 11-15 years was correlated with the clinical outcome (2PD, monofilamenttest). Taking into account the results classified by age presented by Lohmeyer et al. and Mailänder et al., we assessed the correlation between age at injury (0-85 years) and clinical outcome. RESULTS: After 52 of the 56 direct nerve coaptations (93%) normal sensitivity was found with a 2PD<6 mm, 4 times the 2PD was 6 mm. Following nerve grafting a static 2PD of 6-7 mm was measured. Disturbing paresthesia, sensitivity to cold or hypersensitivity were not reported by any patient. The 2PD of the fingers of the opposite uninjured side showed great inter-individual differences. Patient's age and 2PD significantly correlated with significantly poorer results already in the second decade of life. CONCLUSION: In relation to adults, children have an excellent prognosis after nerve reconstruction. The high inter-individual differences in regular sensitivity, depending on age, co-morbi-dities, etc., suggest putting the results of the injured and uninjured sides into relation. Estimation of the Δs2PD may solve this -problem.

Ten-year experience with one-step correction of constriction rings by complete circular resection and linear circumferential skin closure.

BACKGROUND: In amniotic band syndrome (ABS) constriction rings affecting the limbs are regularly seen at birth. Circular resection and closure with multiple Z-plasties has been described as the treatment of choice. However, direct circular closure creating linear circumferential scars might replace multiple Z- or W-plasties to reduce scars and improve aesthetic outcome. METHODS: From 2000 to 2009 we treated 160 patients with ABS. In 43 cases release of isolated constriction rings was performed by circular excision and closure. Constriction rings were completely resected and skin closure could be performed without Z-plasty in all cases. Data from follow-up of all cases were reviewed and photographs and recordings reassessed. The median age at operation was 14.3 months (range 2-32). Constriction rings were localised on the upper arm in five patients, the lower arm in five, the wrist in two and at the metacarpal level in five. At the lower extremity the thigh was affected in three and the lower leg in 23 patients. RESULTS: In the 16 cases of the first treatment period from 2000 to 2004, average follow-up was 6.5 years (range 5.1-10.3). We observed two minor complications following 43 operations (wound dehiscence and secondary healing). No formation recurrence of banding was seen. Aesthetic outcome was overall good. CONCLUSIONS: We found excellent aesthetical and functional results following change of treatment from multiple Z-plasties to linear circumferential closure. Scars were generally less noticeable and no recurrence or scar constriction could be detected with growth. However, radical excision of all constricting tissues prior to wound closure is mandatory.

[Erythropoietin in plastic surgery]. / Erythropoetin in der Plastischen Chirurgie.

EPO is an autologous hormone, which is known to regulate erythropoiesis. For 30 years it has been used for the therapy of diverse forms of anaemia, such as renal anaemia, tumour-related anaemias, etc. Meanwhile, a multitude of scientific publications were able to demonstrate its pro-regenerative effects after trauma. These include short-term effects such as the inhibition of the "primary injury response" or apoptosis, and mid- and long-term effects for example the stimulation of stem cell recruitment, growth factor production, angiogenesis and re-epithelialisation. Known adverse reactions are increases of thromboembolic events and blood pressure, as well as a higher mortality in patients with tumour anaemias treated with EPO. Scientific investigations of EPO in the field of plastic surgery included: free and local flaps, nerve regeneration, wound healing enhancement after dermal thermal injuries and in chronic wounds.Acute evidence for the clinical use of EPO in the field of plastic surgery is still not satisfactory, due to the insufficient number of Good Clinical Practice (GCP)-conform clinical trials. Thus, the initiation of more scientifically sound trials is indicated.

Biomechanical effect of isolated capitate shortening in Kienbock's disease: an anatomical study.

Multiple operations have been proposed to slow the progression of osteonecrosis and secondary carpal damage in Kienböck's disease. To assess the biomechanical changes after capitate shorting, we inserted pressure-testing devices into the carpal and radiocarpal joints in an anatomical study. Pressure sensors were placed into eight thawed non-fixated human cadaver arms to measure the forces transmitted in physiological loading. Longitudinal 9.8 N and 19.6 N forces were applied before and after capitate shortening. After capitate shortening, significant load reduction on the lunate was evident in all specimens. An average decrease of 49% was seen under a 9.8 N load and 56% under a 19.6 N load. The load was transferred to the radial and ulnar intercarpal joints. More relief of pressure on the lunate after isolated capitate shortening is achieved with a shallow angle between the scaphoid and capitate in the posteroanterior radiograph.

Noncontact electrosurgical grounding--a useful and safe tool in the initial surgical management of thermal injuries.

BACKGROUND: Electrosurgical instruments - one of the useful and most-used instruments within the surgeon's armamentarium - are potentially dangerous by causing unanticipated direct burns; fire occurring as a result of electrosurgical instruments and electromagnetic interference with a pacemaker, defibrillator, or cardiac monitoring device. METHODS: The Mega 2000 Patient Return Electrode System produced by Megadyne Medical Products is a noncontact electrode designed to provide adequate electrical return to facilitate function of electrocautery devices. We used this noncontact device in 67 patients (28 women, 39 men) with large burns during their stay in our burn unit and in 11 of these patients (4 women, 7 men) for escharotomies during admission in our burn care. RESULTS: The device functioned well in all cases, no additional cutaneous burns on the patients' body were noticed. CONCLUSION: This paper is a review of our experience with this noncontact electrosurgical grounding in burn surgery highlighting its advantages comparing with the conventional electrosurgical instruments.

Influence of urogenital infections and inflammation on semen quality and male fertility.

BACKGROUND: Urogenital infections and inflammation are a significant etiologic factor in male infertility. METHODS: Data for this review were acquired by a systematic search of the medical literature. Relevant cross-references were also taken into account. RESULTS: We address infectious and inflammatory diseases of different compartments of the male genital tract and discuss their andrological sequelae. Chronic urethritis might be responsible for silent genital tract inflammation with negative impact on semen quality. In chronic pelvic pain syndrome, morphological abnormalities of spermatozoa and seminal plasma alterations are detectable. In the majority of men with epididymitis, a transient impairment of semen quality can be found during the acute infection. However, persistent detrimental effects are not uncommon, even after complete bacteriological cure. The relevance of chronic viral infections as an etiologic factor in male infertility is believed to be underestimated. Data concerning the impact of HIV infection on male fertility are of increasing interest as with the improvement in life expectancy, issues of sexuality and procreation gain importance. Moreover, effects of noninfectious systemic inflammation on the male reproductive tract have to be considered in patients with metabolic syndrome, a disorder of growing relevance worldwide. Finally, microbiological and related diagnostic findings in urine and semen samples are reviewed according to their relevance for male infertility. CONCLUSIONS: Available data provide sufficient evidence that in men with alterations of the ejaculate, urogenital infections and inflammation have to be considered.

[The carotid artery as recipient vessel: troubleshooting for free jejunal transfer after esophagectomy in preradiated patients]. / Gefäßanschluss an die A. carotis communis: Problemlösung bei freier Jejunuminterposition nach Ösophagektomie und Bestrahlung.

BACKGROUND: In the treatment of esophageal cancer neoadjuvant radiotherapy often leads to vascular damage of the usual recipient arteries for free jejunal transfer. End-to-side anastomosis to the carotid artery could be a potential alternative. PATIENTS AND METHODS: A total of 70 patients with locally advanced carcinoma of the esophagus underwent esophagectomy after neoadjuvant radiochemotherapy. In all patients reconstruction was carried out with a free jejunal transfer. Smaller vessels could be used for anastomoses in 54 of these patients and in 16 cases the jejunal flap artery was attached to the carotid artery. RESULTS: Out of 54 patients 9 (17%) with microvascular anastomoses to the smaller vessels needed surgical intervention for ischemia. In 16 patients with anastomosis to the carotid artery no significant failure of perfusion occurred. CONCLUSION: The carotid artery as recipient vessel in free jejunal transfer seems to be a safe therapeutic option for intestinal reconstruction of preradiated esophageal cancer with good functional results.

[Heterotopic ossifications in major burn injuries : An interdisciplinary challenge]. / Heterotope Ossifikationen bei Schwerbrandverletzten : Eine interdisziplinäre Herausforderung.

Heterotopic ossifications in peri-articular tissue can appear after severe head injury, spinal trauma or local joint trauma. Following extensive burns, heterotopic ossifications are a rare, but severe complication with an unknown pathogenesis. In a retrospective analysis of 672 patients who were treated in our burn center over the last 10 years we identified 5 cases (0.74%) of heterotopic ossification.

[Therapy standards after flexor tendon and nerve injuries of the hand: results from a survey of German centres for hand surgery]. / Therapiestandards nach Beugesehnen- und Nervenverletzungen der Hand : Ergebnisse einer Umfrage zur Immobilisationsdauer unter deutschen handchirurgischen Zentren.

BACKGROUND: There is little evidence for the ideal aftercare of combined nerve and flexor tendon injuries of the hand. The aim of this study was to elicit whether concomitant nerve injuries are changing the individual treatment plans after flexor tendon repair in a survey of German centres for hand surgery. METHODS: A questionnaire about aftercare of isolated and combined nerve and flexor tendon injuries of the hand was distributed to members of three German Societies of hand, trauma and plastic surgery. RESULTS: Isolated flexor tendon injuries in zones II to IV are treated by early mobilization in all centres, whereas isolated digital nerve repair is usually followed by immobilization (10% no immobilization, 22.5% up to 1 week, 52.5% for 2 weeks and 15% for 3 weeks). The duration of immobilization increases with lesions of the median or ulnar nerves by about 1 week. In 55% of cases concomitant nerve injury does not influence the early onset of dynamic splinting and mobilization after flexor tendon injuries. CONCLUSION: There seem to be no uniform treatment guidelines for flexor tendon repair if concomitant nerve injury is present. Against the background of the current literature early controlled mobilization after tendon and nerve repair seems to be justified.

Bone mineral density in human immunodeficiency virus-1 infected men with hypogonadism prior to highly-active-antiretroviral-therapy (HAART).

Alterations of bone metabolism have been observed in numerous studies of HIV-infected patients. Sex steroids are known to profoundly influence bone mass and bone turnover. Hypogonadism is common in HIV-infection. Therefore, we performed a cross sectional study of 80 male HIV-infected patients without wasting syndrome, and 20 healthy male controls, in whom we analyzed urine and serum samples for both calciotropic hormones and markers of bone metabolism and of endocrine testicular function. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry both in the lumbar spine and Ward's triangle of the left hip. None of the patients received highly-active-antiretroviral-therapy (HAART). Compared to eugonadal HIV-infected patients, subjects with hypogonadism (n = 32; 40%) showed statistically significant decrease of serum osteocalcin (p < 0.05) and elevated urinary excretion of crosslinks (p < 0.05). However, we found 13 and 15, respectively, patients with osteopenia (t-score -1.0 to -2.5 SD below normal) of the lumbar spine. The dissociation between bone formation and resorption and the reduction of of BMD (p < 0.05) is stronger expressed in patients with hypogonadism. Habitual hypogonadism appears to be of additional relevance for bone metabolism of male HIV-positive patients prior to HAART.

Growth hormone and bone mineral densitiy in HIV-1-infected male subjects.

The aim of this study was to characterize the GH-IGF-I axis of patients with HIV-1-infection without any symptoms of AIDS-associated wasting. A special emphasis was placed on determine bone mineral density (BMD) and biochemical markers of bone metabolism. Therefore 42 male fasting HIV-1-infected outpatients were included and estimation of serum GH, IGF-I, IGFBP-1 and 3, osteocalcin, TNF-alpha, 1,25dihydroxycholecalciferol, and endocrine markers of the gonad function by commercially available RIA's performed. DEXA-measurements of the lumbar spine and the Ward's triangle of the left hip were done. The GH, IGF-1, IGFBP-1 and 3 serum levels were within the normal range Performing Spearman-correlation test, we established significance between IGF-I serum levels and BMD lumbar spine and Ward's triangle (p < 0.01, p < 0.05), CD4 cell-count (p < 0.05), 1,25dihydroxycholecalciferol (p < 0.05), osteocalcin (p < 0.05), TNF-alpha (p < 0.05), body mass index (BMI) (p < 0.05) and total testosterone (p < 0.01). IGFBP-1 correlates both inversely significantly with CD4 cell-count (p < 0.05) and serum-calcium (p < 0.05). The IGFBP-3 correlates with BMI (p < 0.05) and serum osteocalcin (p < 0.05). Correlation both with markers of bone metabolism and vitamin D metabolites showed the important role of GH/IGF-I axis in modulating the availability of calcium in chronic conditions. This axis may be in a part responsible for the manifestation of the HIV-associated osteopenia.

Use of Erythropoietin as adjuvant therapy in nerve reconstruction.

BACKGROUND AND AIMS: Adjuvant therapies may improve the outcome after nerve reconstruction. We analyzed the influence of recombinant human Erythropoietin (rHuEpo), which has proven angiogenic and neuroprotective effects, on the quality of peripheral nerve regeneration. METHODS: Thirty two female Lewis rats underwent nerve reconstruction by means of tubulization (groups I and II) or autologous sciatic nerve grafting (groups III and IV). Groups I and III received daily subcutaneous rHuEpo injections over 2 weeks (1,000 U/kg bw) with normal saline injections as controls (groups II and IV). Data on histology and muscle weight were collected after 7 weeks. Axon count and diameter were assessed by a new method based on digital segmentation. RESULTS: Atrophy of the tibial muscle was less severe in the rHuEpo-treated group compared to controls resulting in significant higher muscle weight quotients (p = 0.006). The same trend was found in the gastrocnemius muscle, but without being statistically significant. No significant differences in axon count or axon diameter were detected in the presence of rHuEpo treatments. CONCLUSION: Our findings give evidence for a positive effect of Erythropoietin on functional recovery after nerve grafting. Muscle recovery benefited from rHuEpo administration despite absence of improved neural morphology. Semi-automated axon detection facilitated accurate morphometrical assessment.

[Management of finger-level avulsion injuries]. / Fingeravulsionsverletzungen.

BACKGROUND: In avulsion-type injuries of the fingers recovery of blood circulation is one of the major obstacles. The indication for finger reconstruction is discussed controversely, being influenced by the patient's needs, the degree of damage to the soft tissue and the prospects of success of the healing process. In this study we present our results after reconstruction of avulsion-type injuries of the fingers. Indications for finger reconstruction will be assessed in consideration of the expected outcome. PATIENTS AND METHODS: From 1999 to 2006 we treated 18 patients with finger level avulsion injuries. 15 casualties were caused by rings and three by ropes looped around a digit. The median age at injury was 23 (12 - 66) years. All patients were examined by an independent observer, who did not participate in the operation. Criteria were functional outcome and patient's complaints and satisfaction. Sensibility was evaluated by 2-point discrimination applying the Greulich star. Finger mobility was assessed with the Buck-Gramcko goniometer. RESULTS: According to the classification of Urbaniak as modified by Kay, 2 patients ranked in class II, 3 in class III and 13 suffered from complete avulsion-amputations (class IV). Of the latter, 8 allowed primary reconstruction of the blood circulation. Two fingers required early or late secondary amputation. After finger reconstruction, patients spent a median time of 18 (12 - 32) days in hospital while primary amputation resulted in a shorter stay of 4 (2 - 5) days. Active motion after replantation in the proximal interphalangeal joint was reduced on average to 64 (25 - 100) degrees. The distal interphalangeal joint nearly ankylosed in all patients following replantation except for one case with an active motion of 40 degrees . Good sensibility could be achieved in one case, protective sensibility in three and none in two patients. All patients with preserved fingers would again decide in favour of finger replantation. CONCLUSION: In specialised centres replantation of complete avulsion-type finger amputations can be achieved. The decision for or against replantation should only be made after microsurgical assessment of the severed soft tissue and in consideration of the patient's specific demands. With the right indication for reconstruction, the patient's satisfaction often outweighs even poor functional outcomes.