This study is the first to show the immunoregulatory effect of VIP in humans, and supports the notion of inhaled VIP as an attractive future therapy to dampen exaggerated immune responses in lung disorders. Thus, the inhalation of neuropeptides may be developed into a new therapeutic principle for chronic inflammatory lung disorders in humans.

Sporadic and hereditary forms of renal cell carcinoma (RCC), von Hippel-Lindau (VHL) disease and the familial paraganglioma syndromes are closely related in terms of their clinical, molecular, and genetic aspects. Most RCCs occur sporadically and the heritable fraction of RCC is estimated to be just 2-4%. An understanding of the molecular genetic basis, the disease-specific and gene-specific biology and the clinical characteristics of these cancer syndromes is of utmost importance for effective genetic diagnosis and appropriate treatment. In addition, such insight will improve our understanding of sporadic RCCs. To date, 10 different heritable RCC syndromes have been described. VHL syndrome is the oldest known hereditary RCC syndrome. Similar to VHL disease, phaeochromocytoma is a major manifestation of the paraganglioma syndromes types 1, 3 and 4 in which RCCs have been reported. These syndromes are therefore regarded as VHL-related disorders and are included in this Review. Multifocal tumours, bilateral occurrence, a young age at diagnosis and/or family history are clinical red flags suggestive of hereditary disease and should trigger referral for genetic and molecular analysis. The identification of an underlying genetic alteration enables gene-specific risk assessment and opens up the possibility of a tailored follow-up strategy and specific surveillance protocols as the basis of effective preventive medicine. The important goals of preventive medicine are to increase the life expectancy of affected patients and to improve their quality of life. The study of seemingly rare hereditary syndromes and their susceptibility genes has consistently revealed clues regarding the aetiology and pathogenesis of these diseases, and can aid diagnosis and the development of therapeutics for patients affected by much more common sporadic counterparts.

pontaneous intracranial hypotension was first described in 1938 by Georges Schaltenbrand, a neurologist in Würzburg, Germany, who named it "hypoliquorrhea" (1, 2). Isolated case reports appeared in the 1940s, and the syndrome has been described many times in print since the mid-1990s (3-9).* Schievink et al. carried out an observational study in the greater Los Angeles area to determine the incidence of SIH. 11 patients with SIH and 23 with spontaneous subarachnoid hemorrhage (SAH) were seen in an emergency department (10, 11). On the basis of an assumed incidence of 10 cases of SAH per 100 000 persons per year, an annual incidence of 5 SIH cases per 100 000 persons was derived.In our neurosurgery department, the number of referrals of patients with SIH and the corresponding catchment area have grown steadily larger: 25 patients with SIH were treated in 2016 and another 25 in 2017, 35 in 2018, and 89 in 2019. Women are affected twice as commonly as men; the average age of onset is 40 years (7,(11)(12).The condition is pathogenetically separated from that of postlumbar puncture headache and from postoperative cerebrospinal fluid (CSF) loss (13). Clinical differential diagnoses include postural orthostatic tachycardia syndrome (POTS), Chiari I malformation, and cervicogenic headache (12, 13). Clinical featuresThe most prominent symptom is positionally dependent headache that is worse in the standing position and tends to increase in severity over the course of the day. Rapid onset is typical: most patients can identify "the day it all began" (14, 15). The positional dependence of the headache, and its being most pronounced in the back of the head, can be explained as the result of the the following causal sequence: low CSF volume-sagging of the brain-tension on the cranial nerves and dura mater. The dura mater of the posterior fossa is especially sensitive to tension (14).

BackgroundPropionibacterium acnes was found in lungs and lymph nodes of patients with sarcoidosis and may induce hypersensitivity type granuloma formation. Data regarding the immune response to P. acnes of European sarcoid patients are scarce.MethodsWe assessed the total IgG and IgA amount and specific antibodies to P. acnes and to Staphylococcus aureus, serving as a control, in BAL fluid of 64 patients with sarcoidosis and of 21 healthy volunteers. In a subcohort of sarcoid patients and controls, TNF-α and GM-CSF production of BAL cells stimulated with heat-killed P. acnes were measured.ResultsIn sarcoid patients, the total IgG and IgA levels in BAL fluid were significantly elevated compared to healthy volunteers. IgG and IgA titres against P. acnes and S. aureus were increased in sarcoid patients, yet based on the total amount of antibodies, only antibodies directed against P. acnes were relatively and significantly increased. Furthermore, BAL cells of sarcoid patients produced significantly more TNF-α and GM-CSF upon stimulation with heat-killed P. acnes compared to controls.ConclusionsPatients with sarcoidosis had elevated levels of specific antibodies against P. acnes which suggest contact with this bacterium in the past. Furthermore, BAL cells of sarcoid patients produced inflammatory cytokines (TNF-α and GM-CSF) upon stimulation with P. acnes indicating potential involvement of this pathogen in the pathogenesis of sarcoidosis in some patients.