Cerebral homeostasis and orthostatic responses in residents of the highest city in the world.

Permanent residence at high-altitude and chronic mountain sickness (CMS) may alter the cerebrovascular homeostasis and orthostatic responses. Healthy male participants living at sea-level (LL; n = 15), 3800 m (HL3800m; n = 13) and 5100 m (HL5100m; n = 17), respectively, and CMS highlanders living at 5100 m (n = 31) were recruited. Middle cerebral artery mean blood flow velocity (MCAv), cerebral oxygen delivery (CDO2), mean blood pressure (MAP), heart rate variability and spontaneuous cardiac baroreflex sensitivity (cBRS) were assessed while sitting, initial 30 s and after 3 min of standing. Cerebral autoregulation index (ARI) was estimated (ΔMCAv%baseline)/ΔMAP%baseline) in response to the orthostatic challenge. Altitude and CMS were associated with hypoxemia and elevated hemoglobin concentration. While sitting, MCAv and LFpower negatively correlated with altitude but were not affected by CMS. CDO2 remained preserved. BRS was comparable across all altitudes, but lower with CMS. Within initial 30 s of standing, altitude and CMS correlated with a lesser ΔMAP while ARI remained unaffected. After 3 min standing, MCAv, CDO2 and cBRS remained preserved across altitudes. The LF/HF ratio increased in HL5100m compared to LL and HL3800m from sitting to standing. In contrary, CMS showed blunted autonomic nervous activation in responses to standing. Despite altitude- and CMS-associated hypoxemia, erythrocytosis and impaired blood pressure regulation (CMS only), cerebral homeostasis remained overall preserved.

Neoadjuvant treatment does not influence PD-L1 expression in stage III non-small-cell lung cancer: a retrospective analysis of tumor samples from the trials SAKK 16/96, 16/00, 16/01, and 16/14.

BACKGROUND: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression. PATIENTS AND METHODS: We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI). RESULTS: Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P > 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar. CONCLUSIONS: In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival.

Early effects of acetazolamide on hemoglobin mass and plasma volume in chronic mountain sickness at 5100 m.

INTRODUCTION AND OBJECTIVES: Chronic Mountain Sickness (CMS) syndrome, combining excessive erythrocytosis and clinical symptoms in highlanders, remains a public health concern in high-altitude areas, especially in the Andes, with limited therapeutic approaches. The objectives of this study were to assess in CMS-highlanders permanently living in La Rinconada (5100-5300 m, Peru, the highest city in the world), the early efficacy of acetazolamide (ACZ) and atorvastatin to reduce hematocrit (Hct), as well as the underlying mechanisms focusing on intravascular volumes. MATERIALS AND METHODS: Forty-one males (46±8 years of age) permanently living in La Rinconada for 15 [10-20] years and suffering from CMS were randomized between ACZ (250 mg once-daily; N = 13), atorvastatin (20 mg once-daily; N = 14) or placebo (N = 14) uptake in a double-blinded parallel study. Hematocrit (primary endpoint) as well as arterial blood gasses, total hemoglobin mass (Hbmass) and intravascular volumes were assessed at baseline and after a mean (±SD) treatment duration of 19±2 days. RESULTS: ACZ increased PaO2 by +13.4% (95% CI: 4.3 to 22.5%) and decreased Hct by -5.2% (95% CI: -8.3 to -2.2%), whereas Hct remained unchanged with placebo or atorvastatin. ACZ tended to decrease Hbmass (-2.6%, 95% CI: -5.7 to 0.5%), decreased total red blood cell volume (RBCV, -5.3%, 95% CI: -10.3 to -0.3%) and increased plasma volume (PV, +17.6%, 95% CI: 4.9 to 30.3%). Atorvastatin had no effect on intravascular volumes, while Hbmass and RBCV increased in the placebo group (+6.1%, 95% CI: 4.2 to 7.9% and +7.0%, 95%CI: 2.7 to 11.4%, respectively). CONCLUSIONS: Short-term ACZ uptake was effective to reduce Hct in CMS-highlanders living at extreme altitude >5,000 m and was associated with both an increase in PV and a reduction in RBCV.

Eryptosis and hemorheological responses to maximal exercise in athletes: Comparison between running and cycling.

We compared the effects of cycling and running exercise on hemorheological and hematological properties, as well as eryptosis markers. Seven endurance-trained subjects randomly performed a progressive and maximal exercise test on a cycle ergometer and a treadmill. Blood was sampled at rest and at the end of the exercise to analyze hematological and blood rheological parameters including hematocrit (Hct), red blood cell (RBC) deformability, aggregation, and blood viscosity. Hemoglobin saturation (SpO2), blood lactate, and glucose levels were also monitored. Red blood cell oxidative stress, calcium content, and phosphatidylserine exposure were determined by flow cytometry to assess eryptosis level. Cycling exercise increased blood viscosity and RBC aggregation whereas it had no significant effect on RBC deformability. In contrast, blood viscosity remained unchanged and RBC deformability increased with running. The increase in Hct, lactate, and glucose concentrations and the loss of weight at the end of exercise were not different between running and cycling. Eryptosis markers were not affected by exercise. A significant drop in SpO2 was noted during running but not during cycling. Our study showed that a progressive and maximal exercise test conducted on a cycle ergometer increased blood viscosity while the same test conducted on a treadmill did not change this parameter because of different RBC rheological behavior between the 2 tests. We also demonstrated that a short maximal exercise does not alter RBC physiology in trained athletes. We suspect that exercise-induced hypoxemia occurring during running could be at the origin of the RBC rheological behavior differences with cycling.

Imaging appearances of Buerger's disease complications in the upper and lower limbs.

Thromboangiitis obliterans (Buerger's disease) is a rare, non-atherosclerotic, segmental, inflammatory vasculitis that most commonly involves small and medium-sized arteries, veins and nerves of the extremities and affects tobacco smokers between the ages of 25 and 45 years. The manifestations of Buerger's disease can be extremely variable and, therefore, awareness of the condition is important for both general and musculoskeletal radiologists. This paper presents the radiological appearance of the sequelae of Buerger's disease involving the upper and lower limbs.

Historical reflections on the afterhyperpolarization--firing rate relation of vertebrate spinal neurons.

In mammalian spinal motoneurons (MNs), the slow component of the afterhyperpolarization (AHP) that follows the spike of each action potential is a major but not the sole determinant of the cells' firing rate. In this brief historical review, we emphasize four points about the AHP-firing rate relation. (1) There is a relatively sparse literature across vertebrates that directly addresses this topic. (2) After the advent of intracellular recording in the early 1950s, there was evidence from mammals to the contrary of an idea that subsequently became prevalent: that the high-firing rates attainable by spinal interneurons (INs) and low-threshold MNs was attributable to their small AHP at rheobase. (3) Further work is needed to determine whether our present findings on the AHP-firing rate relation of turtle cells generalize to the spinal neurons of other vertebrate species. (4) Relevant to point 3, substantial in vivo and in vitro work is potentially available in raw data used in reports on several mammalian and non-mammalian vertebrates. In summary, the factors in addition to the slow AHP that help determine spinal INs and MN firing rate deserve further evaluation across vertebrates, with relevant data already potentially available in several laboratories.

Monostotic fibrous dysplasia of the spine: report of a case involving a cervical vertebra.

Monostotic fibrous dysplasia of the spine is a rare entity. Only 26 cases, of which 11 were located in the cervical spine, are to be found in the literature. We report a 56-year-old male patient with cervicobrachialgia of half year's duration. Radiographs showed a diffuse destruction of the vertebral body and the spinous process of C4. A biopsy of the spinous process confirmed histopathologically a fibrous dysplasia. Due to minor symptoms, no surgical treatment was performed or is planned unless in case of increasing pain, an acute instability or neurological symptoms.

Adductor insertion avulsion syndrome, "thigh splints": relevance of radiological follow-up.

We present a case of chronic osteomyelitis in a 13-year-old girl which was originally diagnosed as adductor insertion avulsion syndrome ("thigh splints") on the basis of the clinical presentation, patient history, initial radiographs and MRI examination. However, at follow-up with persistent pain and altered radiographic and MRI appearances, surgical biopsy was indicated. Histopathological findings confirmed a bone abscess. This case underlines the necessity of clinical follow-up and imaging in certain patients with apparent thigh splints.

Elective neck dissection versus observation in primary parotid carcinoma.

OBJECTIVE: To evaluate the efficacy of elective neck dissection in the clinically negative neck of patients with primary carcinoma of the parotid gland. Study design and setting A retrospective analysis was undertaken at a university Department of Otorhinolaryngology-Head and Neck Surgery on 83 previously untreated patients with primary carcinoma of the parotid gland and a clinically negative neck. The reliability of fine needle aspiration cytology, frozen section, and the clinico-pathologic findings of patients with occult neck metastases were analyzed. The regional recurrence rate and the outcome were compared among 2 groups; one with elective neck dissection (N = 41) and one without elective neck dissection (N = 42). RESULTS: The diagnosis of malignancy was known preoperatively in 59 (71%) cases, the exact histologic tumor type in 36 (43%) and the grade in 37 (44%) of 83 cases. Occult metastases were detected in 8 (20%) of 41 cNO patients, in 5 cases associated with a high-grade and in 3 cases with a low-grade carcinoma. Recurrence of disease developed in 5 (12%) patients in the elective neck dissection group and in 11 (26%) patients in the observation group. All of the 7 neck recurrences occurred in the observation group. The 5-year actuarial and disease-free survival rate was 80% and 86% for patients with elective neck dissection and 83% and 69% for patients without neck dissection. Conclusion and significance A routine elective neck dissection is suggested in all patients with primary carcinoma of the parotid gland. The efficacy of elective neck dissection, nevertheless, has never been evaluated prospectively.

Afterhyperpolarization-firing rate relation of turtle spinal neurons.

This study addressed the afterhyperploarization-firing rate relationship of unanesthetized turtle spinal motoneurons and interneurons. The afterhyperploarization of their solitary action potential at rheobase was compared to that during the cells' minimum and maximum firing rates. Like previous mammalian findings, afterhyperpolarization duration and area at rheobase were 32 and 19% less for high- versus low-threshold motoneurons. Contrariwise, maximum firing rate was two times less for the high-threshold group. Other new findings were that for high- versus low-threshold interneurons, afterhyperpolarization duration and area were 25 and 95% less, and maximum firing rate 21% higher for the high-threshold group. For combined motoneurons versus interneurons, there were no differences in afterhyperpolarization duration and area at rheobase, whereas maximum firing rate was 265% higher for the interneurons. For high-threshold motoneurons alone, there were significant associations between minimum firing rate and afterhyperpolarization duration and area measured at rheobase. In summary, this study showed that (1) the afterhyperploarization values of both turtle spinal motoneurons and interneurons at rheobase provided little indication of their corresponding values at the cells' minimum and maximum firing states, and (2) the evolution of afterhyperploarization from rheobase to maximum firing state differed both qualitatively and quantitatively for motoneurons versus interneurons.

Stewart-Treves syndrome: MR imaging of a postmastectomy upper-limb chronic lymphedema with angiosarcoma.

The rare occurrence of angiosarcoma in postmastectomy upper-limb lymphedema with magnetic resonance (MR) imaging is discussed. Unfamiliarity with this aggressive vascular tumor and its harmless appearance often leads to delayed diagnosis. Angiosarcoma complicating chronic lymphedema may be low in signal intensity on T2-weighting and short tau inversion recovery (STIR) imaging reflecting the densely cellular, fibrous stroma, and sparsely vascularized tumor histology. Additional administration of intravenous contrast medium revealed significant enhancement of the tumorous lesions. Awareness of angiosarcoma and its MR imaging appearance in patients with chronic lymphedema may be a key to early diagnosis or allow at least inclusion in the differential diagnosis.

Mycobacterium marinum: MR imaging and clinical course of a rare soft tissue infection.

Mycobacterium marinum is a rare cause of soft tissue infections. The imposing MR appearance of the soft tissue involvement is in contrast to the chronic painless clinical manifestation.

Intermediate outcome and risk factor assessment of bovine vascular heterografts used as AV-fistulas for hemodialysis access.

OBJECTIVES: This observational study was set up to prospectively follow all bovine heterograft (ProCol) fistulas implanted for hemodialysis access between 1998 and 2002. METHODS: ProCol was implanted if autogenous vein was not available or if patients presented with a history of failed, infected or otherwise complicated ePTFE grafts and/or on immunosuppressive therapy. Fistula patency was the primary outcome; secondary outcomes were clinical events and the rate of access revisions. RESULTS: Sixty-two ProCol grafts were implanted in 56 patients. The mean primary (PP) and secondary patency (SP) was 334 (SEM 57) and 528 (SEM 59) days, respectively. Coronary heart disease was associated with a significantly better SP (OR 0.2, 95% CI 0.1-0.9) whilst diabetes mellitus was associated with a significantly worse SP (OR 0.2, 95% CI 0.1-0.9). Reinterventions were performed at a mean rate of 1.23 (SEM 0.17) per fistula. The relative risk of access revision was significantly higher in patients with diabetes mellitus (OR 9.2, 95% CI 2.3-37.2). CONCLUSIONS: ProCol grafts, used for AV-fistulas, demonstrate acceptable patency rates in high-risk haemodialysis patients. Diabetes mellitus jeopardizes the patency of these fistulas and is associated with a high revision rate.

Early osteoarthritic changes of human femoral head cartilage subsequent to femoro-acetabular impingement.

OBJECTIVE: To use the surgical samples of patients with femoro-acetabular impingement due to a nonspherical head to analyze tissue morphology and early cartilage changes in a mechanical model of hip osteoarthritis (OA). DESIGN: An aberrant nonspherical shape of the femoral head has been assumed to cause an abutment conflict (impingement mechanism) of the hip with subsequent cartilage lesions of the acetabular rim and surface alterations of the nonspherical portion of the head. In this study, 22 samples of the nonspherical portions of the head have been obtained during hip surgery from young adults (mean 30.4 years, range 19-45 years) with an impingement conflict. The samples were first compared with tissue from the same area obtained from six age-matched deceased persons (control group) with normal hip morphology and second with cartilage from 14 older patients with advanced OA. All samples were characterized histologically and hyaline cartilage was graded according to the Mankin criteria. They were further subjected to examination on a molecular basis by immunohistology for cartilage oligomeric matrix protein (COMP), tenascin-C and a collagenase cleavage product (COL2-3/4C(long)) and by in situ hybridization for collagen type I and collagen type II. RESULTS: All samples from the patient group revealed hyaline cartilage with degenerative signs. According to the Mankin criteria, the cartilage alterations were significantly different when compared with the control group (p=0.007) but were less distinct when compared with cartilage from patients with advanced OA (p=0.014). Positive staining and distribution pattern for COMP, tenascin-C and COL2-3/4C(long) showed similarities between the samples from the impingement group and osteoarthritic cartilage but they were distinctly different when compared with healthy cartilage. Levels of collagen I and II transcripts were upregulated in 6 and 10, respectively, of the 14 samples with OA and in 9 and 12, respectively, of the 22 samples from the impingement group. None of the samples from the control group showed upregulation of Collagen I and II mRNA. CONCLUSIONS: The aberrant nonspherical portion of the femoral head in young patients with an impingement conflict consists of hyaline cartilage which shows clear degenerative signs similar to the findings in osteoarthritic cartilage. The tissue alterations are distinctly different when compared with a control group, which substantiates an impingement conflict as an early mechanism for degeneration at the hip joint periphery.

Imaging of chronic recurrent multifocal osteomyelitis of childhood first presenting with isolated primary spinal involvement.

OBJECTIVE: Initial presentation with primary spinal involvement in chronic recurrent multifocal osteomyelitis of childhood (CRMO) is rare. Our objective was to review the imaging appearances of three patients who had CRMO who initially presented with isolated primary spinal involvement. DESIGN AND PATIENTS: The imaging, clinical, laboratory and histology findings of the three patients were retrospectively reviewed. Imaging included seven spinal MR imaging scans, one computed tomography scan, nine bone scans, two tomograms and 16 radiographs. These were reviewed by two musculoskeletal radiologists and a consensus view is reported. All three patients presented with atraumatic spinal pain and had extensive bone spinal pathology. The patients were aged 11, 13 and 12 years. There were two females and one male. RESULTS AND CONCLUSIONS: The initial patient had thoracic T6 and T8 vertebra plana. Bone scan showed additional vertebral body involvement. Follow-up was available over a 3 year period. The second patient had partial collapse of T9 and, 2 years later, of C6. Subsequently extensive multifocal disease ensued and follow-up was available over 8 years. The third patient initially had L3 inferior partial collapse and 1 year later T8 involvement with multifocal disease. Follow-up was available over 3 years. The imaging findings of the three patients include partial and complete vertebra plana with a subchondral line adjacent to endplates associated with bone marrow MR signal alterations. Awareness of the imaging appearances may help the radiologist to include this entity in the differential diagnosis in children who present with spinal pathology and no history of trauma. Histopathological examination excludes tumor and infection but with typical imaging findings may not always be necessary.

Imaging features of pseudoaneurysms of the hand in children and adults.

OBJECTIVE: Our objective was to review the imaging features of pseudoaneurysms of the hand in 25 patients. The patients presented with a mass, peripheral paresthesia, or ischemia. Pseudoaneurysm of the hand is a rare and often clinically unsuspected diagnosis. Correct diagnosis is important because there are risks for distal embolic disease with ischemia or gangrene of the fingers, ulnar or digital nerve dysfunction, rupture, or bone erosion and joint destruction. Scant reports appear in the world literature, and this report is the first review, to our knowledge, of the imaging features. The cause may be a history of a single direct trauma or chronic trauma, as seen in patients with hypothenar or thenar hammer syndrome. CONCLUSION: Awareness of the specific imaging appearances of pseudoaneurysms of the hand and their complications may improve the accuracy of radiologic diagnosis, advance the preoperative workup, and prevent possible clinical complications such as digital gangrene, nerve dysfunction, and aneurysm rupture.

[Clinico-histologic comparison of allogenic and autologous bone-tendon-bone using one-third of the patellar tendon in reconstruction of the anterior cruciate ligament]. / Klinisch-histologischer Vergleich des allogenen und autologen Patellarsehnendrittels (Bone-Tendon-Bone) zur Rekonstruktion des vorderen Kreuzbands.

Reconstruction of the ruptured anterior cruciate ligament (ACL) using modern techniques achieves successful long-term results in up to 90% of all cases. Yet the discussion continues as to the suitable implant to replace the ACL in terms of donor morbidity, implant reaction, long-term results, and potenzial risk of carrier concerning the allograft. The clinical and histological results from 2 years experience with the BPTB allograft (Tutoplast) and the BPTB autograft for ACL reconstruction are compared with reference to stability, functionality, rerupture rate, and histological reaction of the remodelling process. A BTB patella tendon allograft was implanted into 132 patients and a BPTB autograft into 136 patients. The patients were randomly allocated to the two groups. The results were recorded by an independent researcher and assessed according to the IKDC and Lysholm score. In the allograft group, a total of 20 patients (2.6%) reruptured within an average period of 11.75 months. In the autograft group, the transplant reruptured in five patients (4.8%) after an average of 17 months. Histological reappraisal indicated delayed incorporation and extended reconstruction in the BPTB allograft. There were clearer and more protracted indications of hypercellularity and hypervascularity, and the collagen matrix had not regularly aligned longitudinally even 1 year later. A detailed analysis of the BPTB allograft group indicated that especially in young and very sporty patients there is increased elongation of the implant and a clearly higher rerupture rate. Hence, according to the data we have collected, it would seem that the use of the BPTB allograft (Tutoplast) is not suitable especially in young patients who frequently practice high-level sports involving high knee stress.

Isolated amelanotic malignant melanoma of the heart.

We report a 58-year-old woman presenting with dyspnoea and recurrent pulmonary embolism. Echocardiography revealed pericardial effusion and a tumour located in the atrioventricular groove. Surgical exploration showed tumorous infiltration of the ventricle wall and of parts of the atrium. Curative excision was not possible and the operation was discontinued. Histology revealed an amelanotic malignant melanoma. No other tumour location was detected by scanning procedures. This case represents a very rare manifestation of melanoma exclusively located in the atrioventricular groove of the heart leading to recurrent pulmonary embolism. A review of the literature on cardiac involvement of melanoma is provided.