Comparison of acupuncture on specific and non-specific points for the treatment of painful temporomandibular disorders: A randomised controlled trial.

BACKGROUND AND OBJECTIVE: The aim of this single-centre, two-arm, parallel-group, double-blinded, randomised controlled trial was to investigate the disputed specific effectiveness of acupuncture by comparing acupuncture on specific and non-specific points among patients with non-chronic, painful TMDs. METHODS: Following predefined eligibility criteria, 49 consecutive patients of both sexes were recruited to the study. All subjects were diagnosed with a non-chronic (Graded Chronic Pain Scale grade <3) painful TMD, as assessed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Patients were randomly assigned to group A (acupuncture on specific points) or group B (acupuncture on non-specific points) after the initial examination (T0). Both acupuncture treatment sessions were conducted by a trained dentist once a week for four weeks. The examination was repeated five weeks (T5) after T0 by one calibrated examiner who was unaware of the study groups. Characteristic pain intensity (CPI) was evaluated as the main outcome criterion and compared between times and treatment groups by means of non-parametric tests (significance level set at P = .05). Secondary outcomes comprised the maximum corrected active mouth-opening without pain (MAO); patients' expectations regarding acupuncture treatment and pain development; depressivity; and oral health-related quality of life (OHRQoL). RESULTS: A total of 41 patients (38 female) successfully completed the study (mean age: 40.17 ± 16.61). The two groups did not differ significantly at any time in terms of age and CPI. However, CPI was significantly (P < .05) lower at T5 than at T0 for both groups (29.66 and 30.35% lower in group A and group B, respectively). An increase in MAO was observed at T5 for both groups but was significant for group B only (P = .016). All patients had positive expectations of acupuncture therapy, and the two groups did not differ significantly at T5 with regard to the extent to which their expectations had been fulfilled by the treatment (P = .717). Comparison of T0 and T5 showed a statistically significant reduction of depressivity for group A (P = .0205), but no significant change for group B (P = .329). At T5, OHRQoL had improved significantly for both groups (group A, P = .018; group B, P < .001) compared with at T0. CONCLUSIONS: Acupuncture on both specific and non-specific points reduces the non-dysfunctional pain of TMD patients. The effect of acupuncture on painful TMD cannot be attributed to the specific point selection.

Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2).

PURPOSE: The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancer patients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy. METHODS: Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter. According to the statistical design, recruitment was scheduled in groups of three patients in order not to miss a more than 33% frequency of dose-limiting adverse events (DL-AE) prior to dose escalation. RESULTS: Twenty-three patients were recruited, and all planned dose levels were applied. During the actual trial period of 4 ± 1 weeks, three patients experienced six DL-AEs altogether (leucopenia, neutropenia, asthenia, anemia) possibly related to ART (not exceeding 33% in any dose level). CONCLUSIONS: Up to 200 mg/d (2.2-3.9 mg/kg/d) oral ART were safe and well tolerated; therefore, 200 mg/d are recommended for phase II/III trials. Safety monitoring should include reticulocytes, NTproBNP, as well as audiological and neurological exploration.

L-Shaped Septal Extension Spreader Graft for Improvement of Tip Symmetry in Unilateral Cleft Lip Nose Deformities.

INTRODUCTION: The unilateral cleft lip nose is characterized by numerous complex and interdependent deformities. Secondary rhinoplasty techniques aim to correct cleft lip nose deformities by using multiple maneuvers combining septum and nasal spine medialization and alar cartilage, as well as soft tissue mobilization and repositioning. Moreover, cartilage grafting is frequently used to restore adequate tip projection and nasal symmetry. We present a technique of cartilage grafting commonly used in noncleft rhinoplasties that we modified for cases of moderate cleft lip nose deformities. PATIENTS AND METHODS: We present a retrospective case study of 21 patients with moderate unilateral cleft lip nose deformities who underwent secondary septorhinoplasty with an L-shaped septal extension spreader graft combined with alar rim, alar batten graft, and soft tissue repositioning. Exclusion criteria were severe or complex septal deviation avoiding a stable fixation of the graft. Mean follow-up time was 28 months. Surgical outcomes were analyzed by anthropometric measurements of standardized preoperative and postoperative photographs. RESULTS: All parameters improved except for the nostril height. The height between the alar base and the dome defining dome symmetry, as well as the angles between the lower lateral cartilage and the alar base (α) defining the orientation of the alar rim, improved significantly. The mean ratios of cleft/noncleft side of the height between the alar base and the dome and α showed statistically significant improvements from 0.833 (preoperative) to 0.994 (postoperative) (P < 0.0001) and from 0.883 to 1.02 (P = 0.0038), respectively. CONCLUSIONS: The L-shaped septal extension spreader graft combined with alar batten graft and soft tissue repositioning is an option for secondary rhinoplasties in unilateral cleft lip nose deformities minimizing tip rigidity with significant improvement of the dome's height and its symmetry, as well as the alar side angle.

Three-dimensional endoscopic visualization in functional endoscopic sinus surgery.

Three-dimensional (3D) stereoscopic vision in sinus surgery has been achieved with the microscope so far. The introduction of two-dimensional (2D) endoscopes set a milestone in the visualization of the surgical field and paved the way to functional endoscopic sinus surgery (FESS), although the 2D endoscopes cannot provide a stereoscopic visualization. The latest technology of 3D endoscopes allows stereoscopic vision. We provide a clinical investigation of all commercially available 3D endoscopes in FESS to compare their clinical value and efficacy to routinely used conventional 2D HD endoscopes. In this prospective, randomized, controlled clinical study, 46 patients with polypoid chronic rhinosinusitis underwent FESS with one of the following three endoscopes: 2D 0° high definition (HD), 3D 0° standard definition (SD) and 3D 0° HD. Four surgeons qualitatively assessed endoscopes on stereoscopic depth perception (SDP) of the surgeon, sharpness and brightness of the image, as well as their comfort in use during surgery. Surgeons assessed the brightness of the control (2D HD) significantly better than 3D SD (p = 0.009) and brightness of 3D HD was rated significantly better than 3D SD (p = 0.038). Stereoscopic depth perception (SDP) of 3D SD was assessed highly significantly better than the control (2D HD) (p = 0.021), whereas 3D HD displayed best SDP (p = 0.0001). The comfort in use was rated significantly higher in the 3D HD group compared to the control group (p = 0.025). No significant differences in sharpness could be seen among all endoscopes. 3D HD endoscopy provides an improvement in SDP and brightness of the surgical field. It enhances the intraoperative visualization and is therefore an important and efficient development in endoscopic sinus surgery.

Pericranial Flap for Inner Lining in Nasal Reconstruction.

INTRODUCTION: The general principle in nasal reconstruction is to reconstruct the 3 layers of skin, cartilage, and mucosa. Reconstructing the inner lining remains a challenge especially when adjacent tissues are not available after tumor resection. The galea and pericranial flaps (PFs) are widely used in anterior skull base reconstructive surgery.We evaluated the use of the PF for the inner nasal lining in an anatomical cadaver study and present its clinical application in patients with benign and malignant tumors of the nose and anterior skull base. METHODS: Four fresh cadavers were injected with red-colored silicone for determining the pattern of vascularization of supraorbital (SOA) and supratrochlear (STA) arteries of each PF. Four surgical cases (2 nasocranial meningiomas, 1 nasal melanoma, and 1 nasal squamous cell carcinoma) received PF for reconstruction of inner lining. RESULTS: The median distances between the superior orbital rim and the division of the deep and superficial branches of STA and SOA were 8 ± 3.3 mm and 8 ± 3.7 mm, respectively. The maximum measured distance was 11 mm. The SOA provided the longest axial vascularization (70.7 ± 13. 9 mm) compared with STA (35 ± 10.4 mm). Median length of PF for subtotal nasal reconstruction including tip and columella were 70 ± 5 mm and 22.5 ± 3.5 mm, respectively.Three cases were successfully reconstructed with PF up to the distal border of the upper lateral cartilage. In 1 patient, distal necrosis of tip and columella occurred. CONCLUSIONS: The blood supply of the PF is mainly based on the SOA arteries. Thus, superficial dissection must end 15 mm above the orbital rim to ensure the survival of the flap. Pericranial flap can be applied for inner lining in combined nasocranial, septal, and nasal defects with extension down to the distal border of the upper lateral cartilage. Vascularization is reliable in flaps up to a length of 70 mm.

In vivo expression profile of the antiviral restriction factor and tumor-targeting antigen CD317/BST-2/HM1.24/tetherin in humans.

Human CD317 is an intrinsic immunity factor that restricts the release of enveloped viruses, including the major pathogens HIV and Lassa virus, from infected cells in culture. Its importance for infection control in humans is unclear, due in part to its incompletely defined in vivo expression pattern. CD317 also has been proposed as a selective target for immunotherapy of multiple myeloma. To provide a framework for studies of the biological functions, regulation, and therapeutic potential of CD317, we performed microarray-based expression profiling in 468 tissue samples from 25 healthy organs from more than 210 patients. We found that CD317 protein was expressed to varying degrees in all organs tested and detected in a number of specialized cell types, including hepatocytes, pneumocytes, ducts of major salivary glands, pancreas and kidney, Paneth cells, epithelia, Leydig cells, plasma cells, bone marrow stromal cells, monocytes, and vascular endothelium. Although many of these cell types are in vivo targets for pathogenic viruses, restriction by CD317 or virus-encoded antagonists has been documented in only some of them. Limited cell type-dependent coexpression of CD317 with the IFN biomarker MxA in vivo and lack of responsive stimulation in organ explants suggest that interferons may only partially regulate CD317. This in vivo expression profiling sheds light on the biology and species-specificity of CD317, identifies multiple thus far unknown interaction sites of viruses with this restriction factor, and refutes the concept of its restricted constitutive expression and primary IFN inducibility. CD317's widespread expression calls into question its suitability as a target for immunotherapy.

Identification of a human Th1-like IFNγ-secreting Treg subtype deriving from effector T cells.

Characteristics and function of effector T-cells with regulatory properties (induced Treg, "iTreg") in humans are ill defined. Here we report that a proportion of activated, initially CD4(+)CD25(-)CD127(+) effector T-cells from human peripheral blood can convert into T-cells with regulatory activity while concomitantly secreting IFNγ. Upon short-term culture in vitro these cells expressed a panel of common Treg markers, including FOXP3, CD25, GITR, HLA-DR and CTLA-4 in parallel with the Th1-specific transcription factor T-bet. Despite their own IFNγ secretion they effectively suppressed IFNγ secretion in effector T cells in parallel with inhibition of their proliferation. Highly purified IFNγ(+)iTreg shared many functional properties with nTreg: Their suppressive activity was antigen-independent, contact-mediated and cytokine-independent. Of note, in contrast to nTreg an inhibitor of TGF-ß1 signalling promoted the proliferation of IFNγ(+)iTreg, without abrogating their suppressive function. In addition in vivo in tonsils of patients with chronic tonsillitis an IFNγ-secreting subpopulation of the CD4(+)CD25(-)CD127(+)CD45RA(-) memory T helper cell population was detected, which exhibited regulatory properties as well. Our results support the existence of Th1-like adaptive Tregs in humans that express a robust regulatory phenotype, comparable to nTreg and at the same time share characteristics of Th1 cells. According to our in vitro data IFNγ(+)iTreg can emerge from activated effector T cells and downregulate Th1-mediated immune responses, supporting the hypothesis of effector T cell plasticity as a means for proper initiation and self regulation of inflammatory processes. This report characterizes a new subpopulation of human adaptive regulatory T-cells that derive from effector Th-cells and concomitantly express Th1-specific T-bet and IFNγ with Foxp3.

Acupuncture as Complementary Treatment for Acute Tinnitus: A Randomized Controlled Pilot Study.

BACKGROUND: Up to now, tinnitus has been an almost non-treatable symptom affecting more than 18% of the population in industrialized countries. So far, there are only a few studies evaluating the effectiveness of acupuncture in tinnitus treatment, none of which include acute tinnitus (<3 months). The aim of this pilot study was to explore the feasibility of recruitment and adherence to acupuncture conducted according to the principles of traditional Chinese medicine in patients with acute idiopathic tinnitus and to assess effect sizes on subjective and objective outcomes within a randomized controlled design. PATIENTS AND METHODS: After randomization patients of the control group received usual care (n = 23), and patients of the intervention group (n = 25) received 4 additional acupuncture treatments in a 4- to 6-week period. Tinnitus severity was assessed by means of a visual analogue scale as well as standardized and validated tinnitus questionnaires (Tinnitus Functional Index and 12-item Mini Tinnitus Questionnaire) at baseline and 6 weeks after. These subjective parameters were completed by tone audiometry. Comparisons of the groups were carried out using the Wilcoxon-Mann-Whitney test. RESULTS: Both groups were comparable without significant differences in baseline values. All outcomes, except for the overall well-being, showed better improvements in the intervention group with clinically significant differences from baseline to end point. However, among the outcomes only the subjective change in tinnitus severity showed a significant group difference. No serious side effects were observed. CONCLUSION: The design of our pilot study was feasible in terms of recruitment, although patient adherence to treatment remained challenging. However, considering the small intergroup differences, procedures regarding the numbers of acupuncture sessions and the total period of the acupuncture treatment should be reconsidered. The results of this pilot study provide a good basis for future confirmatory trials.

Biological signature characteristics of primary isolates from human immunodeficiency virus type 1 group O in ex vivo human tonsil histocultures.

Human immunodeficiency virus type 1 (HIV-1) group M viruses have achieved a global distribution, while HIV-1 group O viruses are endemic only in particular regions of Africa. Here, we evaluated biological characteristics of group O and group M viruses in ex vivo models of HIV-1 infection. The replicative capacity and ability to induce CD4 T-cell depletion of eight group O and seven group M primary isolates were monitored in cultures of human peripheral blood mononuclear cells and tonsil explants. Comparative and longitudinal infection studies revealed HIV-1 group-specific activity patterns: CCR5-using (R5) viruses from group M varied considerably in their replicative capacity but showed similar levels of cytopathicity. In contrast, R5 isolates from group O were relatively uniform in their replicative fitness but displayed a high and unprecedented variability in their potential to deplete CD4 T cells. Two R5 group O isolates were identified that cause massive depletion of CD4 T cells, to an extent comparable to CXCR4-using viruses and not documented for any R5 isolate from group M. Intergroup comparisons found a five- to eightfold lower replicative fitness of isolates from group O than for isolates from group M yet a similar overall intrinsic pathogenicity in tonsil cultures. This study establishes biological ex vivo characteristics of HIV-1 group O primary isolates. The current findings challenge the belief that a grossly reduced replicative fitness or inherently impaired cytopathicity of viruses from this group underlies their low global prevalence.

Induction of CD4+ T-cell anergy and apoptosis by activated human B cells.

B cells are well-known mediators of humoral immunity and serve as costimulators in the generation of T cell-mediated responses. In several mouse models, however, it was observed that B cells can also down-regulate immune reactions, suggesting a dual role for B cells. Due to this discrepancy and so far limited data, we directly tested the effects of primary human B cells on activated CD4(+) T helper cells in vitro. We found that under optimal costimulation large, activated CD25(+) B cells but not small CD25(-) B cells induced temporary T-cell anergy, determined by cell division arrest and down-regulation of cytokine production. In addition, large CD25(+) B cells directly induced CD95-independent apoptosis in a subpopulation of activated T cells. Suppression required direct B-T-cell contact and was not transferable from T to T cell, excluding potential involvement of regulatory T cells. Moreover, inhibitory effects involved an IL-2-dependent mechanism, since decreasing concentrations of IL-2 led to a shift from inhibitory toward costimulatory effects triggered by B cells. We conclude that activated CD25(+) B cells are able to costimulate or down-regulate T-cell responses, depending on activation status and environmental conditions that might also influence their pathophysiological impact.

Pharmacogenomic identification of c-Myc/Max-regulated genes associated with cytotoxicity of artesunate towards human colon, ovarian and lung cancer cell lines.

Development of novel therapy strategies is one of the major pressing topics of clinical oncology to overcome drug resistance of tumors. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We applied a gene-hunting approach using microarray-based transcriptome-wide mRNA expression profiling and COMPARE analyses. We identified a set of genes, whose expression was associated either with high IC50 values or low IC50 values for ART. Therefore, these genes may function as resistance or sensitivity factors for response of tumor cells towards ART. This viewpoint is conceivable for genes involved in ribosomal activity, drug transport, cellular antioxidant defense, apoptosis, cell proliferation, cell cycle progression etc. An investigation of underlying signal transduction by pathway analysis suggested a role of the signaling pathways related to tumor necrosis factor (TNF) and the tumor suppressor p53. On the other hand, there were genes without obvious functional link to cellular response to ART, such as genes involved in the survival of cochlear outer and inner hair cells etc. We proved the hypothesis that ART influences the activity of transcription factors regulating downstream genes involved or not involved in response of cancer cells towards ART. This would explain the identification of genes with and without obvious relation to the cytotoxic activity of ART by microarray and COMPARE analyses. By analysis of the binding motifs for the transcription factors c-Myc and Max, we indeed found that 53 of 56 genes contained one or more binding sites for c-Myc/Max upstream of the gene-location. We conclude that c-Myc and Max-mediated transcriptional control of gene expression might contribute to the therapeutic effects of ART in cancer cells, but may also confer unwanted side effects by affecting therapy-unrelated genes.

Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo.

BACKGROUND: HIV-1 Nef critically contributes to AIDS in part by augmenting virus titers in infected individuals. Analyzing which of Nef's activities contribute to HIV pathogenesis has been hampered by the lack of a cell culture model in which Nef exerts pronounced effects on HIV replication. The human lymphoid aggregate culture (HLAC) from tonsil maintains the cell populations and cytokine milieu found in vivo, supports a productive infection without exogenous stimulation, and Nef contributes to efficient HIV-1 replication as well as CD4+ T cell depletion in this experimental ex vivo-model. RESULTS: To identify determinants in Nef that mediate these activities, we infected HLAC with a panel of isogenic HIV-1NL4-3 strains that encode for well-characterized mutants of HIV-1SF2 Nef. Determination of HIV-1 replication revealed that enhancement of the virus spread by Nef is governed by a complex set of protein interaction surfaces. In contrast, increased CD4+ T lymphocyte depletion depended on only two protein interaction surfaces in Nef that mediate either downregulation of cell surface CD4 or interaction with the NAKC signalosome. Consistently, in HLAC from 9 out of 14 donors, Nef enhanced CD4+ T cell depletion in the absence of a significant effect on virus replication. Moreover, our results suggest that this Nef-dependent enhancement in depletion occurred predominately in uninfected bystander CD4+ T cells. CONCLUSION: Our findings suggest that Nef facilitates depletion of CD4+ T lymphocytes in HIV-1-infected lymphoid tissue ex vivo by increasing the pool of productively infected cells and by sensitizing bystander cells for killing. This ability might contribute to Nef's pathogenic potential in vivo.

Additional use of acupuncture to NSAID effectively reduces post-tonsillectomy pain.

Post-tonsillectomy swallowing pain is a common and distressing side effect after tonsillectomy and thus of great clinical interest. Up until now, there is no randomized controlled patient- and observer-blinded study evaluating the efficacy of acupuncture against swallowing pain after tonsillectomy. We therefore compared the potency of specific verum acupuncture points related to a Chinese medical diagnosis in reducing postoperative swallowing pain with non-specific control points on the body as well as a non-acupuncture group who received standard medication only. The standardized pain therapy after tonsillectomy was orally administered nonsteroidal anti-inflammatory drugs (NSAID) (diclofenac 3 x 50 mg oral). The patients (n = 123) treated with NSAID were asked about their acute pain after taking a sip of water between the first and fifth postoperative day. Participants' pain was assessed using visual analog (VAS) [zero (0) for no pain up to ten (10) for the acute reported outset pain] before and 20 min, 1, 2 and 3 h after acupuncture treatment or standard pain medication, respectively. The functional assessment of diagnosis and treatment point-combination occurred by means of the "Heidelberg Model" of Traditional Chinese Medicine (TCM). Verum acupuncture lead to a significant additional pain relief. In comparison to the acupuncture, they also reported an average of 3 h duration of adequate pain-relief past taking the NSAID. This trial strongly supports a specific acupuncture scheme for the treatment of postoperative swallowing pain after tonsillectomy. It may particularly serve as an alternative pain treatment in case of NSAID intolerances.

Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2).

BACKGROUND: The antimalarial artesunate (ART), a semisynthetic derivative of artemisinin from the Chinese herb artemisia annua has remarkable anticancer properties in vitro and in vivo. Its excellent safety profile known from short-term therapy in malaria was confirmed in an open phase I trial (ARTIC M33/2) for dose-finding as add-on therapy for four weeks. PURPOSE: Patients with metastatic breast cancer, who had not experienced any clinically relevant adverse events (AE) during participation in ARTIC M33/2, were offered to continue ART as compassionate use (CU). Regular monitoring was continued in order to ensure adequate individual safety and tolerability and to collect information about long-term treatment with ART. Clinically relevant AEs or second progression of disease during ART were reasons for discontinuation of the add-on therapy. STUDY DESIGN: Compassionate use was offered open-label to participants of ARTIC M33/2. METHODS: Patients continued to take 100, 150 or 200 mg oral ART daily as add-on therapy to their guideline-based oncological therapy. Clinical and laboratory monitoring included audiological and neurological examination, ECG, NTproBNP and reticulocyte determination. Cumulative treatment days and cumulative ART doses encompass both the phase I study as well as the continued add-on treatment period (CU). RESULTS: Following the 4 ±â€¯1 weeks of the phase I trial, thirteen patients continued the add-on therapy as CU, resulting in a total of 3825 treatment days. In individual patients up to 1115 cumulative treatment days (37 months) and cumulative ART doses up to 167.3 g were reached. A total of 25 AEs grade ≥ 2 at least possibly related to ART long-term add-on therapy were documented, two, six and 17 in dose groups 100, 150 and 200 mg/d ART respectively. Six of these AEs were classified as grade 3, two in patients taking 150 and four in patients on 200 mg/d, none of them being probably or certainly related to ART. CONCLUSIONS: In thirteen patients with metastatic breast cancer up to 200 mg/d long-term oral ART (2.3-4.1 mg/kg BW/d) in up to 1115 cumulative treatment days (37 months) did not result in any major safety concerns.

Are human ATP-binding cassette transporter C11 and earwax associated with the incidence of cholesteatoma?

Cholesteatoma is an ear disease based on a locally destructive noncancerous conglomerate of epidermis and keratin debris. Abnormal growth of stratified keratinized squamous epithelium in the temporal bone causes destruction of the outer and middle ear, potentially leading to hearing impairment, facial palsy, vertigo, lateral sinus thrombosis, and intracranial complications. Although cholesteatoma is effectively treated by surgical resection (mastoidectomy), the lack of effective and nonsurgical therapies potentially results in fatal consequences, establishing the need for a comprehensive investigation of cholesteatoma pathogenesis. Although its etiology is still being debated, interestingly, we found that the trend associated with the 538G allele frequency of the adenosine triphosphate-binding cassette transporter C11 (ABCC11) gene, the determinant of wet-type earwax, and ethnic groups was similar to that between the incidence of cholesteatoma and ethnic groups (countries). The incidences of cholesteatoma in Europe (Denmark, Finland, and Scotland) are higher than in East Asia (Japan), and the frequencies of the ABCC11 538G allele in African, American, and European (Finland and Scotland) populations are higher than those in East Asian populations (Japan). Additionally, a single-nucleotide polymorphism in the ABCC11 gene (rs17822931, 538G > A; Gly180Arg) is closely related to earwax morphotypes. While earwax is often beneficial to ear health, it is sometimes harmful in cases where it causes hearing impairment. Based on independent findings of associations between ABCC11 and the physiological environment of the auditory canal, we hypothesize a possible link between ABCC11, earwax, and the incidence of cholesteatoma.

Randomized study exploring the combination of radiotherapy with two types of acupuncture treatment (ROSETTA): study protocol for a randomized controlled trial.

BACKGROUND: Adverse effects such as fatigue, pain, erythema, nausea and vomiting are commonly known in patients undergoing irradiation (RT) alone or in combination with chemotherapy (RCHT). Patients suffering from these symptoms are limited in their daily life and their quality of life (QOL) is often reduced. As addressed in several trials, acupuncture can cause amelioration of these specific disorders. Especially for pain symptoms, several groups have shown efficacy of acupuncture. To what extent the difference between traditional acupuncture (verum acupuncture) and false acupuncture (sham acupuncture) is in reducing side effects and improvement of QOL is not clear. METHODS/DESIGN: ROSETTA is a prospective randomized phase II trial (version 1.0) to examine the efficacy of traditional acupuncture in patients with RT-related side effects. In the experimental (verum) arm (n = 37) an experienced acupuncture-trained person will treat dedicated acupuncture points. In the control (sham) arm (n = 37) sham acupuncture will be performed to provide a blinded comparison of results. DISCUSSION: This is the first randomized prospective trial to evaluate the effect of traditional acupuncture on RT-related side effects such as fatigue and QOL. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02674646 . Registered on 8 December 2015.

Correction of severe columella and tip retraction in silicone implanted Asian short noses.

BACKGROUND: Silicone Implants and other alloplastic materials are frequently used in rhinoplasty to augment Asian short noses. However, nasal deformities as a result of implant-related infections are increasing in incidence. The resulting tissue scarrings hinder the application of traditional techniques of lengthening short noses. The following paper presents a technique to correct severe postoperative retractions of the tip and columella caused by silicone implants. METHODS: We present a retrospective case study of two Asian patients with recurrent acute infections, secondary to silicone dorsum implants, leading to chronic inflammation of the tip and columella. The treatment consisted of implant removal and the immediate nasal reconstruction by combining uni- or bilateral gingivobuccal flaps along with L-shaped costal cartilage grafting. To evaluate the surgical results, various anthropometric measurements, particularly the nasal length (NL) and nasal tip projection (NTP) of pre- and postoperative profile photographs, were analyzed. RESULTS: Successful nasal lengthening and correction of columellar retraction were achieved. In case I, postoperative NTP and NL increased by 34.7% and 21.1%, respectively. In case II, NL and NTP increased by 23.8% and 10.6%, respectively. However, case II presented necrosis of the distal extremity of one gingivobuccal flap without rib graft resorption, which later healed by secondary intention. CONCLUSION: Pronounced columellar retraction in severe short noses can be successfully managed with a combination of gingivobuccal flaps along with L-shaped costal cartilage grafting. The use of autologous materials decreases the risk of long-term extrusion through the tip. The gingivobuccal flap provides vascularity to the exposed rib cartilage on the columella and prevents its resorption.

Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study.

PURPOSE: Artesunate (ART) has been used for a long time in the treatment of Plasmodium falciparum malaria and has been considered safe. The present phase I study aimed to determine the daily dose of ART that is well tolerated as add-on therapy in patients with breast cancer for 4 weeks of therapy. Ototoxicity could be a potential safety concern in settings different from malaria. Therefore, comprehensive audiological assessment was essential. METHODS: The ARTIC M33/2 study was a prospective, open, uncontrolled, monocentric phase I dose-escalation study to evaluate the safety and tolerability of ART in patients with advanced breast cancer. Patients received either 100, 150 or 200 mg oral ART daily for a test phase of 4 weeks as add-on therapy to their ongoing oncological treatment. For the investigation of the safety of ART for hearing, an audiological assessment was performed with each patient before the intake of ART and after 4 weeks of therapy. RESULTS: Twenty-three female patients were included in the study. During the test phase, four patients had adverse events (AEs) of the auditory system possibly related to the intake of ART. However, none of these AEs was classified as severe AE (SAE) and did not require treatment interruption. Four patients had AEs concerning the vestibular system (vertigo) during the test phase, one of which was classified as SAE. However, the SAE was fully reversible after discontinuation of ART. CONCLUSION: None of the audiological results after 4 weeks of therapy with ART showed any dose-limiting auditory toxicity. However, audiological monitoring in further clinical studies with prolonged use of oral ART in doses up to 200 mg daily is warranted. The ARTIC M33/2 study is registered at eudract.ema.europa.eu with the Number 2007-004432-23 and at clinicaltrials.gov with the Number NCT00764036.

Measurable impact of acupuncture on mucosal swelling of inferior turbinates: a prospective, randomized, controlled study.

CONCLUSIONS: Sham acupuncture turned out to be more effective than expected. The effect of acupuncture cannot be assessed by optical rhinometry (ORM). OBJECTIVES: In most cases nasal congestion is caused by hypertrophy of the inferior turbinate as a result of allergic and chronic rhinitis. Topical decongestants cause severe side effects. As a consequence, there is an increasing demand for alternative treatment options such as traditional Chinese medicine (TCM). METHODS: A total of 25 patients with nasal congestion due to hypertrophic inferior turbinate were recruited. The mucosal swelling status of the inferior turbinate was assessed by continuous ORM for 20 min. Patients were asked to score the severity of their nasal congestion on a visual analogue scale (VAS) before and 10 and 20 min after acupuncture. Specific verum acupuncture points related to nasal congestion were tested against non-specific control sham acupuncture points. RESULTS: Sham acupuncture improved VAS scores, whereas ORM measured an increase in nasal swelling. The ORM revealed a quicker onset of the effect of verum acupuncture on the nasal blood flow. Also, verum acupuncture reaches its maximum effect in a shorter time period, so that the net reaction time was much shorter. However, ORM could not prove a decongestant effect of verum acupuncture on inferior turbinate.

SAMHD1's protein expression profile in humans.

The deoxynucleoside triphosphate triphosphohydrolase and 3' → 5' exonuclease SAMHD1 restricts HIV-1 infection in noncycling hematopoietic cells in vitro, and SAMHD1 mutations are associated with AGS. Little is known about the in vivo expression and functional regulation of this cellular factor. Here, we first assessed the SAMHD1 protein expression profile on a microarray of 25 human tissues from >210 donors and in purified primary cell populations. In vivo, SAMHD1 was expressed in the majority of nucleated cells of hematopoietic origin, including tissue-resident macrophages, DCs, pDCs, all developmental stages of thymic T cells, monocytes, NK cells, as well as at lower levels in B cells. Of note, SAMHD1 was abundantly expressed in HIV target cells residing in the anogenital mucosa, providing a basis for its evaluation as a cellular factor that may impact the efficiency of HIV transmission. Next, we examined the effect of the activation status and proinflammatory cytokine treatment of cells on expression and phosphorylation of SAMHD1. Activated, HIV-susceptible CD4(+) T cells carried pSAMHD1(T592), whereas resting CD4(+) T cells and macrophages expressed the unphosphorylated protein with HIV-restrictive activity. Surprisingly, stimulation of these primary cells with IFN-α, IFN-γ, IL-4, IL-6, IL-12, IL-18, IL-27, or TNF-α affected neither SAMHD1 expression levels nor threonine 592 phosphorylation. Only IL-1ß moderately down-regulated SAMHD1 in activated CD4(+) T cells. Taken together, this study establishes the first cross-sectional protein expression profile of SAMHD1 in human tissues and provides insight into its cell cycle-dependent phosphorylation and unresponsiveness to multiple proinflammatory cytokines.