Man flu is not a thing - Gender-specific secondary analysis of a prospective randomized-controlled trial for acute rhinosinusitis.

BACKGROUND: 'Man flu' is a popular term to describe hypersensitivity to acute rhinosinusitis (ARS) in men. While this pop-cultural description may influence the social perspective of ARS, so far, no prospective observational data on the gender-specific natural development of ARS is available. METHODS: Secondary data analyses were performed from the placebo arm of a prospective, interventional phase IV clinical trial. Objective measurement of ARS symptoms were assessed with the Major Symptom Score (MSS), a clinician-rated assessment tool. The Sino-Nasal Outcome Test-22 (SNOT-22) was used for symptom self-report. Repeated measures analysis of variance (ANOVA) with gender as a group variable were used to investigate changes in MMS and SNOT-22 total score and subscales over time. RESULTS: While MMS scores did not differ at baseline, women showed a significantly greater reduction than men with a medium effect size (p = .040) over time. In the patient-reported symptom score, women showed a significantly higher symptom load at baseline (p = .038), but also a significantly faster subjective improvement of symptoms than men during the course of time with a medium effect size (p = .020). However, when separately assessing the SNOT-22 subscales, a significant time*gender effect was only found for emotional symptoms (p = .047). No gender effect was found for neither nasal, otological, or sleep symptoms (all p > .05). DISCUSSION: Although a certain gender difference was found both in the clinician- as well as patient-rated ARS symptoms, the hypothesis of a 'man flu' should be disregarded. Gender differences in ARS symptomatology should be carefully evaluated without stigmatizing symptom distress based on gender perceptions.

[Polyneuropathies in vasculitis and connective tissue diseases : Clinical manifestations and diagnostic recommendations]. / Polyneuropathien bei Vaskulitiden und Kollagenosen : Klinische Manifestationen und diagnostische Empfehlungen.

Vasculitic neuropathies result from inflammation of the vasa nervorum followed by ischemia and destruction of the peripheral nerve. The inflammation can be systemic or localized, i.e. non-systemic. Systemic vasculitis can be divided into primary and secondary forms. The latter is associated with, e.g. connective tissue diseases, infections, cancer or induced by certain drugs. Around two thirds of patients with systemic vasculitis develop vasculitic neuropathy presenting as characteristic painful, multifocal mononeuropathy of acute onset. The group of non-systemic neuropathies has grown in recent years with the addition of diabetic and non-diabetic lumbosacral radiculoplexus neuropathies, among others. Within the group of connective tissue diseases, other non-vasculitic neuropathies can occur as nerve-entrapment syndromes and sensory ataxic neuropathy. The aim of this article is to present a condensed overview of neuropathies associated with vasculitis and connective tissue diseases and to communicate characteristic clinical symptoms supporting rapid diagnostic and therapeutic procedures.

Novel SBF2 mutations and clinical spectrum of Charcot-Marie-Tooth neuropathy type 4B2.

Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), a sensorimotor neuropathy with autosomal recessive inheritance and association with glaucoma. Since the discovery of the gene mutation, only few additional patients have been reported. We identified seven CMT4B2 families with nine different SBF2 mutations. Revisiting genetic and clinical data from our cohort and the literature, SBF2 variants were private mutations, including exon-deletion and de novo variants. The neuropathy typically started in the first decade after normal early motor development, was predominantly motor and had a rather moderate course. Electrophysiology and nerve biopsies indicated demyelination and excess myelin outfoldings constituted a characteristic feature. While neuropathy was >90% penetrant at age 10 years, glaucoma was absent in ~40% of cases but sometimes developed with age. Consequently, SBF2 mutation analysis should not be restricted to individuals with coincident neuropathy and glaucoma, and CMT4B2 patients without glaucoma should be followed for increased intraocular pressure. The presence of exon-deletion and de novo mutations demands comprehensive mutation scanning and family studies to ensure appropriate diagnostic approaches and genetic counseling.

Early-Onset Myopathies: Clinical Findings, Prevalence of Subgroups and Diagnostic Approach in a Single Neuromuscular Referral Center in Germany.

BACKGROUND: Early-onset myopathies are a heterogeneous group of neuromuscular diseases with broad clinical, genetic and histopathological overlap. The diagnostic approach has considerably changed since high throughput genetic methods (next generation sequencing, NGS) became available. OBJECTIVE: We present diagnostic subgroups in a single neuromuscular referral center and describe an algorithm for the diagnostic work-up. METHODS: The diagnostic approach of 98 index patients was retrospectively analysed. In 56 cases targeted sequencing of a known gene was performed, in 44 patients NGS was performed using large muscle specific panels, and in 12 individuals whole exome sequencing (WES) was undertaken. One patient was diagnosed via array CGH. Clinical features of all patients are provided. RESULTS: The final diagnosis could be found in 63 out of 98 patients (64%) with molecular genetic analysis. In 55% targeted gene sequencing could establish the genetic diagnosis. However, this rate largely depended on the presence of distinct histological or clinical features. NGS (large myopathy-related panels and WES) revealed genetic diagnosis in 58.5% (52% and 67%, respectively). The genes detected by WES in our cohort of patients were all covered by the panels. Based on our findings we propose an algorithm for a practical diagnostic approach.Prevalences:MTM1- and LAMA2-patients are the two biggest subgroups, followed by SEPN1-, RYR1- and Collagen VI-related diseases. 31% of genetically confirmed cases represents a group with overlap between "congenital myopathies (CM)" and "congenital muscular dystrophies (CMD)". In 36% of the patients a specific genetic diagnosis could not be assigned. CONCLUSIONS: A final diagnosis can be confirmed by high throughput genetic analysis in 58.5% of the cases, which is a higher rate than reported in the literature for muscle biopsy and should in many cases be considered as a first diagnostic tool. NGS cannot replace neuromuscular expertise and a close discussion with the geneticists on NGS is mandatory. Targeted candidate gene sequencing still plays a role in selected cases with highly suspicious clinical or histological features. There is a relevant clinical and genetic overlap between the entities CM and CMD.

Allogeneic hematopoietic cell transplantation outcomes for children with B-precursor acute lymphoblastic leukemia and early or late BM relapse.

Large registry studies have shown superior disease-free survival (DFS) with matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT) over chemotherapy alone for patients with B-precursor acute lymphoblastic leukemia (ALL) and a late BM relapse. As most of these patients will not have an MSD, the decision to pursue an unrelated allo-HCT in second remission (CR2) or await a future relapse and perform HCT in third remission (CR3) continues to be debated. Between 1990 and 2006, 41 children with relapsed B-precursor ALL received a myeloablative allo-HCT at the University of Minnesota. Graft sources consisted of matched related donor (n=11), matched unrelated donor (n=9), and unrelated umbilical cord blood (n=21). Before allo-HCT, 15 patients had an early relapse (<36 months from diagnosis) and 26 had an initial late relapse (36 months from diagnosis). In all, 30 patients (73%) were in CR2 and 11 were in CR3 (27%) at time of allo-HCT. Five year OS/DFS were similar for patients with an early or late marrow relapse, but there was inferior DFS among late-relapse patients transplanted in CR3 compared with CR2 (30% vs 75%, P=0.04). These results suggest that allo-HCT should be pursued in children after a first marrow relapse, rather than waiting for subsequent recurrence.

[Operative treatment of proximal humeral fractures with helix wire]. / Operative Versorgung proximaler Humerusfrakturen mit Titanwendel.

BACKGROUND: Between 1 January 2000 and 31 December 2002, a total of 50 patients with a dislocated or unstable fracture of the proximal humerus were treated surgically with a titanium helix wire introduced retrogradely into the medullary cavity. MATERIAL AND METHODS: Fracture classification showed 8 cases of a two-fragment fracture, 32 cases of a three-fragment fracture, and 10 cases of a so-called four-fragment fracture. A retrospective radiographic and medical review of all 50 patients showed postoperative complications in 24% of the cases; in 8 cases (16%) secondary loss of retention occurred with consecutive projection of the helix wires into the subacromial joint space. There were two cases each (4%) of perforation of the helix wire into the joint space without loss of retention and fracture dehiscence because of a blocking mechanism by the helix wire in the subcapital fracture gap. The postoperative revision rate was 18% (9/50) as a result. Of 50 patients with a titanium helix wire, 38 (76%) were reviewed after an average of 23 months (12-31). Radiologically partial necrosis of the head of the humerus was seen in two patients and there was necrosis of the head of the humerus with pseudarthrosis in one patient, which had a negative effect on the Constant score. RESULTS: Because of a change of procedure (n=5) and intercurrent deaths (n=5) only 2 of 12 patients, in whom complications had occurred postoperatively, could be followed up clinically; the results of the follow-up are sure to be distorted by this selection effect. Of 38 patients, 32 (84%) showed very good to good results functionally; the average Constant score was 74 points and the average age- and sex-specific corrected score was 92%. DISCUSSION: Thus, the procedure does not achieve better functional results compared to other rigid and semirigid internal fixation methods while it has a high complication and revision rate compared to other rigid and semirigid internal fixation methods. Moreover, early functional treatment is not possible so that the titanium helix wire represents a retention aid rather than stable internal fixation. Overall we cannot recommend the procedure for the operative management of proximal humerus fractures further and have abandoned it ourselves.

Autologous stem cell transplantation for high-risk Ewing's sarcoma and other pediatric solid tumors.

The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose-response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these high-risk patients is yet to be conclusively determined. We have transplanted 36 patients on two consecutive protocols with a variety of histological diagnoses. Overall survival (OS) was 63% (95% CI: 47-79%) at 1 year and 33% (95% CI: 16-50%) at 3 years. Patients with a diagnosis of Ewing's sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) had significantly better survival than those with other diagnoses with estimated 3-year OS of 54% (95% CI: 29-79%) for this group of patients (P = 0.03). There were two transplant-related deaths both attributable to hepatic veno-occlusive disease. Median follow-up among survivors is 3.5 years (range: 0.6-7.9 years). These data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT.

Respiratory insufficiency as a presenting symptom of LGMD2D in adulthood.

Several forms of recessive limb girdle muscular dystrophy (LGMD2C-F) are due to mutations in genes coding for sarcoglycans. Clinically, most sarcoglycanopathies present in childhood with skeletal muscle wasting and early loss of ambulation; respiratory insufficiency is rare. However, some cases of LGMD2D with a late onset and a milder course have been reported. In this study, two adult brothers, compound heterozygous for two missense mutations of the SGCA gene (Arg77Cys, Val247Met), presented with respiratory insufficiency while they were still ambulatory.

Successful treatment of muscle sarcoidosis with thalidomide.

A 36-year-old male patient suffered from therapy resistant sarcoidosis with long-standing contractures, myopathy, skin lesions and pulmonary changes. Low-dose therapy with thalidomide (50 mg/day) was well tolerated, and the patient rapidly improved. Thalidomide was effective for muscular, cutaneous, and pulmonary involvement in our patient. This is the first report on the efficacy of thalidomide in muscle sarcoidosis. Therefore, thalidomide may become a second-line agent in patients with severe muscle and skin involvement, but further studies are warranted.

Characterization of neuronal nicotinic acetylcholine receptors in the membrane of unmyelinated human C-fiber axons by in vitro studies.

Application of acetylcholine to peripheral nerve terminals in the skin is a widely used test in studies of human small-fiber functions. However, a detailed pharmacological profile and the subunit composition of nicotinic acetylcholine receptors in human C-fiber axons are not known. In the present study, we recorded acetylcholine-induced changes of the excitability and of the intracellular Ca2+ concentration in C-fiber axons of isolated human nerve segments. In addition, using immunohistochemistry, an antibody of a subtype of nicotinic acetylcholine receptor was tested. Acetylcholine and agonists reduced the current necessary for the generation of action potentials in C fibers by > 5-Iodo-A-85380 > 1,1-dimethyl-4-phenylpiperazinium iodide > nicotine > cytisine > acetylcholine; choline had no effect. The epibatidine-induced increase in axonal excitability was blocked by mecamylamine and, less efficiently, by methyllycacontine and dihydro-beta-erythroidine. Many C-fiber axons were labeled by an antibody that recognizes the alpha5 subunit of nicotinic acetylcholine receptors. In summary, electrophysiological and immunohistochemical data indicate the functional expression of nicotinic acetylcholine receptors composed of alpha3, alpha5, and beta4 but not of alpha4/beta2 or of alpha7 subunits in the axonal membrane of unmyelinated human C fibers. In addition, the observations suggest that the axonal membrane of C fibers in isolated segments of human sural nerve can be used as a model for presumed cholinergic chemosensitivity of axonal terminals.

[Diagnosis and therapy of vasculitic neuropathy. Consensus statement of the German Centers for Neuromuscular Disease]. / Klinik, Diagnostik und Therapie der vaskulitischen Neuropathie. Bundeseinheitliche Konsensuspapiere der Muskelzentren im Auftrag der Deutschen Gesellschaft für Muskelkranke e. V. (DGM).

Vasculitic neuropathies are immune mediated diseases of the peripheral nervous system, in which inflammation of the blood vessels causes damage to the nerves. We distinguish neuropathies associated with primary and secondary systemic vasculitis, with rheumatic diseases, with malignant disorders, drug-induced vasculitis and the non-systemic vasculitic neuropathies (NSVN). The typical clinical picture consists in an asymmetric or multifocal, painful sensorimotor neuropathy with an acute, subacute or chronic course and acute relapses. Neurophysiology reveals an active, asymmetric, axonal sensorimotor neuropathy. The disorders usually respond to immunosuppressive treatment. A diagnosis of definite vasculitis can be made with evidence of vasculitis in a biopsy specimen. The absence of positive morphological evidence, however, does not exclude the diagnosis. There is no single laboratory test that can prove or exclude vasculitis, in NSVN even an elaborate panel of blood tests can show normal findings. Systemic vasculitis has an incidence of 4/100,000 per year and, untreated, has a poor prognosis, which is greatly improved by the use of immunosuppressive treatment. The prognosis of NSVN is generally better, although many patients need long term immunosuppression. Current treatment recommendations for vasculitic neuropathies are presented.

Lymphedema after sentinel lymphadenectomy for breast carcinoma.

BACKGROUND: Initial studies of sentinel lymphadenectomy for patients with breast carcinoma confirmed that the status of the sentinel lymph nodes was an accurate predictor of the presence of metastatic disease in the axillary lymph nodes. Sentinel lymphadenectomy, as an axillary staging procedure, has risks of morbidity that have yet to be defined. METHODS: Patients were enrolled in a two-phase protocol that included concurrent data collection of patient characteristics and treatment variables. During the first (validation) phase, 72 patients underwent sentinel lymph node excision followed by a level I-II axillary dissection. After the technique had been established, the second phase commenced, during which only patients with positive sentinel lymph nodes underwent an axillary dissection. RESULTS: During the second phase, lymphedema was identified in 9 of 303 patients (3.0%) who underwent sentinel lymphadenectomy alone and in 20 of 117 patients (17.1%) who underwent sentinel lymphadenectomy combined with axillary dissection (P < 0.0001). Of 303 patients who underwent sentinel lymphadenectomy alone, 8 of 155 patients (5.1%) with tumors located in the upper outer quadrant and 1 of 148 patients (0.7%) with tumors in other locations developed lymphedema (P = 0.012). CONCLUSIONS: The risk of developing lymphedema after undergoing sentinel lymphadenectomy was measurable but significantly lower than after undergoing axillary dissection. Tumor location in the upper outer quadrant and postoperative trauma and/or infection were identifiable risk factors for lymphedema.

Role of high-dose chemotherapy with hematopoietic stem cell rescue in the treatment of metastatic or recurrent rhabdomyosarcoma.

PURPOSE: This review summarizes the published data on the use of high-dose chemotherapy and hematopoietic stem cell rescue (HSCR) in the treatment of recurrent or metastatic rhabdomyosarcoma (RMS). PATIENTS AND METHODS: Three hundred eighty-nine patients were identified from 22 articles selected by computer generated searching of MEDLINE (1979-present). One hundred seventy-seven patients had stage 4 disease and were treated during first complete remission (CRI). The remaining patients were treated during CR1/first partial remission (PR1) (110 patients), CR2/PR2 (53 patients), CR2 (12 patients), CR3 (1 patient), or treated with disease (36 patients). RESULTS: Patients treated during CR1 or CR1/PR1 had event-free survival (EFS) rates ranging from 24% to 29% at 3 to 6 years from diagnosis and overall survival (OS) rates ranging from 20% to 40% at 2 to 6 years after diagnosis according to data provided as Kaplan-Meier estimates. Studies without Kaplan-Meier estimates (n = 32) indicate that 12 patients (38%) with stage IV RMS treated during CR1 or CR1/PR1 were surviving 7 to 60 months from diagnosis, similar to patients with stage IV RMS treated on Intergroup Rhabdomyosarcoma Studies II or III. Patients treated during CR2, CR3, or with evidence of disease had a worse outcome with an estimated 3 years OS of 12% (n = 51). Studies without Kaplan-Meier estimates (n = 27) indicate that four patients (15%) treated during CR2, CR3, or with disease were surviving 17 to 33 months after transplant. CONCLUSIONS: Based on these data, there does not appear to be a significant advantage to undergoing high-dose chemotherapy with HSCR for patients with relapsed or refractory high-risk RMS. Clearly, there is a need for incorporating new treatment strategies for patients with high-risk RMS.

In vitro tumor-pulsed or in vivo Flt3 ligand-generated dendritic cells provide protection against acute myelogenous leukemia in nontransplanted or syngeneic bone marrow-transplanted mice.

To determine whether immune stimulation could reduce acute myelogenous leukemia (AML) lethality, dendritic cells (DCs) were pulsed with AML antigens and used as vaccines or generated in vivo by Flt3 ligand (Flt3L), a potent stimulator of DC and natural killer (NK) cell generation. Mice were then challenged with AML cells. The total number of splenic anti-AML cytotoxic T-lymphocyte precursors (CTLPs) present at the time of challenge was increased 1.9-fold and 16.4-fold by Flt3L or DC tumor vaccines, respectively. As compared with the 0% survival of controls, 63% or more of recipients of pulsed DCs or Flt3L survived long term. Mice given AML cells prior to DC vaccines or Flt3L had only a slight survival advantage versus non-treated controls. NK cells or NK cells and T cells were found to be involved in the antitumor responses of Flt3L or DCs, respectively. DC vaccines lead to long-term memory responses but Flt3L does not. Syngeneic bone marrow transplantation (BMT) recipients were analyzed beginning 2 months post-BMT. In contrast to the uniform lethality in BMT controls given AML cells, recipients of either Flt3L or DC vaccines had a significant increase in survival. The total number of splenic anti-AML CTLPs at the time of AML challenge in BMT controls was 40% of concurrently analyzed non-BMT controls. Flt3L or DC vaccines increased the total anti-AML CTLPs 1.4-fold and 6.8-fold, respectively. Neither approach was successful when initiated after AML challenge. It was concluded that DC vaccines and Flt3L administration can enhance an AML response in non-transplanted or syngeneic BMT mice but only when initiated prior to AML progression.

Surgical management of symptomatic spinal metastases. Postoperative outcome and quality of life.

STUDY DESIGN: Eighty-six surgical interventions in 76 consecutive patients with symptomatic spinal metastases were reviewed retrospectively. OBJECTIVES: To evaluate the postoperative outcome and quality of life of patients surgically treated for symptomatic spinal metastases. SUMMARY OF BACKGROUND DATA: The standard surgical treatment for patients with symptomatic spinal metastases is anterior spinal cord decompression with stabilization. However, because therapy is only palliative, satisfactory quality of life and high patient acceptance are essential. METHODS: The medical records of all patients were reviewed retrospectively. Furthermore, all surviving patients or the next of kin of deceased patients were interviewed by telephone, and the family doctors or the care-providing physicians of external institutions were contacted. RESULTS: First-choice surgical treatment was anterior spinal cord decompression with stabilization. Postoperative mean survival was 13.1 months, and mean time at home after spinal surgery was 11.1 months. Neurologic improvement with regard to Frankel classification was observed in 58% of the patients, and 93% were able to walk postoperatively. Pain relief was noted in 89%. Overall, 67% of the patients achieved moderate or good general health as shown by the Karnofsky Index, and 80% were satisfied or very satisfied with the surgical intervention. Moreover, 19% of the surgical interventions were associated with complications, local tumor recurrence developed in 22% of the patients, and paraplegia ultimately developed in 18% of patients. CONCLUSIONS: Surgical management of symptomatic spinal metastases, in particular anterior decompression, is of benefit in most metastatic lesions in terms of satisfactory postoperative outcome and quality of life. However, in patients with melanoma or lung carcinoma, the authors advocate spinal surgery only in very exceptional cases.