Browsing by Subject "ADULT PATIENTS"

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  • Mäntylä, Jarkko; Mazur, Witold; Törölä, Tanja; Bergman, Paula; Saarinen, Tuomas; Kauppi, Paula (2019)
    Background: By definition bronchiectasis (BE) means destructed structure of normal bronchus as a consequence of frequent bacterial infections and inflammation. In many senses, BE is a neglected orphan disease. A recent pan-European registry study, EMBARC, has been set up in order to better understand its pathophysiology, better phenotype patients, and to individualize their management. Aim: To examine the aetiology and co-morbidity of BE in the capital area in Finland. Methods: Two hundred five patients with BE diagnosis and follow up visits between 2016 and 2017 in Helsinki University Hospital were invited to participate in the study. Baseline demographics, lung functions, imaging, microbiological, and therapeutic data, together with co-morbidities were entered into EMBARC database. Clinical characteristics, aetiologic factors, co-morbidities, and risk factors for extensive BE were explored. Results: To the study included 95 adult patients and seventy nine percent of the BE patients were women. The mean age was 69 years (SD +/- 13). Asthma was a comorbid condition in 68% of the patients but in 26% it was estimated to be the cause of BE. Asthma was aetiological factor for BE if it had been diagnosed earlier than BE. As 41% BE were idiopathic, in 11% the disorder was postinfectious and others were associated to rheumatic disease, Alpha-1-antitrypsin deficiency, IgG deficiency and Kartagener syndrome. The most common co-morbidities in addition to asthma were cardiovascular disease (30%), gastroesophageal reflux disease (26%), overweight (22%), diabetes (16%), inactive neoplasia (15%), and immunodeficiency (12%). Extensive BE was found in 68% of BE patients in whom four or more lobes were affected. Risk factors for extensive BE were asthma (OR 2.7), asthma as aetiology for BE (OR 4.3), and rhinosinusitis (OR 3.1). Conclusions: Asthma was associated to BE in 68% and it was estimated as aetiology in every fourth patient. However, retrospectively, it is difficult to exclude asthma as a background cause in patients with asthma-like symptoms and respiratory infections. We propose asthma as an aetiology factor for BE if it is diagnosed earlier than BE. Asthma and rhinosinusitis were predictive for extensive BE.
  • Tosetto, Alberto; Badiee, Zahra; Baghaipour, Mohammad-Reza; Baronciani, Luciano; Battle, Javier; Berntorp, Erik; Bodo, Imre; Budde, Ulrich; Castaman, Giancarlo; Eikenboom, Jeroen C. J.; Eshghi, Peyman; Ettorre, Cosimo; Goodeve, Anne; Goudemand, Jenny; Richard, Charles; Hay, Morris; Hoorfar, Hamid; Karimi, Mehran; Keikhaei, Bijan; Lassila, Riitta; Leebeek, Frank W. G.; Fernandez, Maria Fernanda Lopez; Mannucci, Pier Mannuccio; Mazzucconi, Maria Gabriella; Morfini, Massimo; Oldenburg, Johannes; Peake, Ian; Lopez, Rafael Parra; Peyvandi, Flora; Schneppenheim, Reinhard; Tiede, Andreas; Toogeh, Gholamreza; Trossaert, Marc; Zekavat, Omidreza; Zetterberg, Eva M. K.; Federici, Augusto B. (2020)
    Background Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. Aims To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VWD patients to investigate any possible clustering of bleeding symptoms within type 3 patients. Methods We compared the bleeding phenotype and computed the bleeding score (BS) using the MCMDM-1VWD bleeding questionnaire in patients enrolled in the 3WINTERS-IPS and MCMDM-1VWD studies. Results In 223 unrelated type 3 VWD patients, both the BS and the number of clinically relevant bleeding symptoms were increased in type 3 as compared to type 1 VWD patients (15 versus 6 and 5 versus 3). Intracranial bleeding, oral cavity, hemarthroses, and deep hematomas were at least five-fold over-represented in type 3 VWD. A more severe bleeding phenotype was evident in patients having von Willebrand factor antigen levels <20 IU/dL at diagnosis in the two merged cohorts. In type 3 patients, there was an apparent clustering of hemarthrosis with gastrointestinal bleeding and epistaxis, whereas bleeding after surgery or tooth extraction clusters with oral bleeding and menorrhagia. Conclusions In the largest cohort of type 3 VWD patients, we were able to describe a distinct clinical phenotype that is associated with the presence of a more severe hemostatic defect.
  • Lezo, Antonella; Diamanti, Antonella; Marinier, Evelyne M.; Tabbers, Merit; Guz-Mark, Anat; Gandullia, Paolo; Spagnuolo, Maria I.; Protheroe, Sue; Peretti, Noel; Merras-Salmio, Laura; Hulst, Jessie M.; Kolacek, Sanja; Ee, Looi C.; Lawrence, Joanna; Hind, Jonathan; D'Antiga, Lorenzo; Verlato, Giovanna; Pukite, Ieva; Di Leo, Grazia; Vanuytsel, Tim; Doitchinova-Simeonova, Maryana K.; Ellegard, Lars; Masconale, Luisa; Maiz-Jimenez, Maria; Cooper, Sheldon C.; Brillanti, Giorgia; Nardi, Elena; Sasdelli, Anna S.; Lal, Simon; Pironi, Loris (2022)
    Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1-4 and 14-18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < -2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.
  • Uutela, Pauliina; Passweg, Jakob; Halter, Jorg; Weiger, Roland; Waltimo, Tuomas; Mauramo, Matti (2019)
    Objectives The purpose of this study was to compare the prevalence of common oral diseases between allogeneic haematopoietic stem cell transplantation (HSCT) recipients and healthy controls. Materials and methods A total of 143 adult allogeneic HSCT recipients who were treated for haematological malignancies between 2008 and 2016 were included in the study. The HSCT recipients were age and sex matched with healthy controls. A dental examination was performed on the HSCT recipients prior to HSCT. Differences in stimulated saliva flow rate (SSFR), decayed, missing and filled teeth (DMFT) index, number of teeth, number of caries lesions, and measures of current or previous periodontitis (radiological attachment loss >3 mm or probing pocket depth >= 4 mm) between HSCT recipients and controls were examined. Results Stimulated saliva flow rate, DMFT index and the number of caries lesions were poorer in the HSCT recipients pre-HSCT compared to controls (all P-values
  • Cork, Michael J.; Eckert, Laurent; Simpson, Eric L.; Armstrong, April; Barbarot, Sebastien; Puig, Luis; Girolomoni, Giampiero; de Bruin-Weller, Marjolein; Wollenberg, Andreas; Kataoka, Yoko; Remitz, Anita; Beissert, Stefan; Mastey, Vera; Ardeleanu, Marius; Chen, Zhen; Gadkari, Abhijit; Chao, Jingdong (2020)
    Background: Atopic dermatitis (AD) profoundly affects quality of life (QoL). Dupilumab significantly improves clinical outcomes, is well tolerated, and approved to treat inadequately controlled moderate-to-severe AD in adults; however, its effect on patient-reported outcomes (PROs) is not fully characterized. Objective: To evaluate the impact of dupilumab on patient-reported AD symptoms and QoL. Methods: Pooled data were analyzed from two identically designed phase 3 studies, LIBERTY AD SOLO 1 (NCT02277743) and SOLO 2 (NCT02277769), assessing the following PROs: Peak Pruritus Numerical Rating Scale (NRS), Pruritus Categorical Scale, SCORing AD (SCORAD), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Hospital Anxiety and Depression Scale (HADS), five-dimension EuroQoL questionnaire (EQ-5D), and patient-assessed disease status and treatment effectiveness. Results: Dupilumab rapidly improved (vs. placebo) Peak Pruritus NRS scores by day 2 (p <.05), anxiety and depression (HADS), and QoL (DLQI) by week 2, and maintained through week 16 (p <.0001). At week 16, more dupilumab-treated than placebo-treated patients reported improvement in SCORAD itch and sleep, and no pain/discomfort (EQ-5D) (p <.0001). Limitations: Cultural differences of translated PROs. Conclusion: Dupilumab had a significant, positive impact on AD symptoms, including itch, sleep, pain, anxiety and depression, and QoL in adults with moderate-to-severe AD.
  • Kristensen, Peter L.; Pedersen-Bjergaard, Ulrik; Due-Andersen, Rikke; Hoi-Hansen, Thomas; Grimmeshave, Lise; Lyssenko, Valeriya; Groop, Leif; Holst, Jens J.; Vaag, Allan A.; Thorsteinsson, Birger (2016)
    Introduction: In healthy carriers of the T allele of the transcription factor 7-like 2 (TCF7L2), fasting plasma glucagon concentrations are lower compared with those with the C allele. We hypothesised that presence of the T allele is associated with a diminished glucagon response during hypoglycaemia and a higher frequency of severe hypoglycaemia (SH) in type 1 diabetes (T1DM). Material and methods: This is a post hoc study of an earlier prospective observational study of SH and four mechanistic studies of physiological responses to hypoglycaemia. 269 patients with T1DM were followed in a one-year observational study. A log-linear negative binomial model was applied with events of SH as dependent variable and TCF7L2 alleles as explanatory variable. In four experimental studies including 65 people, TCF7L2 genotyping was done and plasma glucagon concentration during experimental hypoglycaemia was determined. Results: Incidences of SH were TT 0.54, TC 0.98 and CC 1.01 episodes per patient-year with no significant difference between groups. During experimental hypoglycaemia, the TCF7L2 polymorphism did not influence glucagon secretion. Discussion: Patients with T1DM carrying the T allele of the TCF7L2 polymorphism do not exhibit diminished glucagon response during hypoglycaemia and are not at increased risk of severe hypoglycaemia compared with carriers of the C allele.
  • Jain, Ruchi; Ozgumus, Turkuler; Jensen, Troels Mygind; du Plessis, Elsa; Keindl, Magdalena; Moller, Cathrine Laustrup; Falhammar, Henrik; Nystrom, Thomas; Catrina, Sergiu-Bogdan; Jorneskog, Gun; Jessen, Leon Eyrich; Forsblom, Carol; Haukka, Jani K.; Groop, Per-Henrik; Rossing, Peter; Groop, Leif; Eliasson, Mats; Eliasson, Bjorn; Brismar, Kerstin; Al-Majdoub, Mahmoud; Nilsson, Peter M.; Taskinen, Marja-Riitta; Ferrannini, Ele; Spegel, Peter; Berg, Tore Julsrud; Lyssenko, Valeriya (2020)
    Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual beta-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
  • Kyrklund, Kristiina; Pakarinen, Mikko P.; Rintala, Risto J. (2017)
    Anorectal malformations are an important group of congenital anomalies that vary widely in their anatomical characteristics and complexity. Understanding the long-term functional outcomes after modern treatments, and how these compare to the general population, are essential for ensuring that patients receive optimal, evidence-based care. With increasing appreciation of the wider impact of the illness on patients and their families, minimizing social disability from fecal incontinence and enabling normal social integration from the outset are key management concerns. This review summarizes the current knowledge on the functional outcomes by type of malformation, reflecting on the literature, and our institutional experience over a follow-up period of nearly 30 years. (C) 2017 Elsevier Inc. All rights reserved.
  • Nyholm, Iiris; Hukkinen, Maria; Koivusalo, Antti; Merras-Salmio, Laura; Kolho, Kaija-Leena; Rintala, Risto J.; Pakarinen, Mikko P. (2019)
    Background and Aims Childhood-onset ulcerative colitis [UC] requires total colectomy in one-quarter of patients at some point of their disease. The study objective was to evaluate long-term outcomes after proctocolectomy with ileoanal anastomosis [IAA] for paediatric UC. Methods Medical records of all children undergoing proctocolectomy with IAA for UC during 1985-2016 in Helsinki University Hospital were retrospectively assessed. Data on disease history, diagnostic and operative details, occurrence of surgical complications, functional outcome, postoperative diagnosis of Crohn's disease [CD] and pouch failure were collected. Risk factors for IAA failure were analysed with Cox regression. Results Of 87 patients, 85 [98%] had UC and 2 [2%] inflammatory bowel disease unclassified [IBD-U] preoperatively. Altogether 66% underwent two-stage and 34% underwent three-stage procedures. During 7.8 [4.1-14.5] years' follow-up, nine [10%] patients were diagnosed with postoperative CD. Postoperative leakages [n = 8, 9%] and strictures [n = 10, 11%] were equally common, whereas fistulas [78% vs 9%, p Conclusions For paediatric UC, long-term surgical and functional outcomes after proctocolectomy with IAA are reassuring. Need for three-stage surgery and occurrence of postoperative fistulas and abscesses, but not leakages or strictures, associate with postoperative CD diagnosis and the risk for ileostomy.
  • Orlanski-Meyer, Esther; Topf-Olivestone, Chani; Ledder, Oren; Dotan, Iris; Folmer-Hansen, Lars; Kindermann, Angelika; Assa, Amit; Kolho, Kaija-Leena; Kolacek, Sanja; Carroll, Matthew W.; Strisciuglio, Caterina; Aloi, Marina; Hansen, Richard; Navon, Dan; Winter, Harland S.; Navas-Lopez, Victor M.; de Ridder, Lissy; Smets, Francoise; Weiss, Batia; Turner, Dan (2020)
    Introduction: Contemporary pediatric data on pouch outcomes are sparse, especially in the era of laparoscopic surgeries. We aimed to assess outcomes and predictors in children with ulcerative colitis/inflammatory bowel disease (IBD)-unclassified who underwent colectomy and ileal pouch-anal anastomosis. Methods: This was a multicenter retrospective cohort study from 17 IBD centers affiliated with the pediatric IBD Porto group of ESPGHAN. An electronic REDcap system was used to collate baseline characteristics, demographic, clinical, management and surgical data, short- and long-term outcomes, and to identify potential predictors of pouch outcome. Results: Of the 129 patients included, 86 (67%) developed pouchitis during follow-up of median 40 months (interquartile range 26-72), of whom 33 (26%) with chronic pouchitis. Patients operated on by surgeons performing
  • Barrenetxea Lekue, Cristina; Grasso Cicala, Silvina; Leppä, Sirpa; Stauffer Larsen, Thomas; Herráez Rodríguez, Susana; Alonso Caballero, Clara; Jørgensen, Judit M.; Toldbod, Helle; Leal Martínez, Irene; D’Amore, Francesco (2019)
    Outcomes for patients with non-Hodgkin’s lymphoma (NHL) that proves refractory to treatment remain poor. Treatment of such patients is individualized and can include enrolment in a clinical trial of novel agents or use of one of a wide array of drug regimens. Initial treatment with anthracyclines such as doxorubicin limits options at later stages of treatment because of anthracycline-related cumulative cardiotoxicity. The aza-anthracenedione pixantrone was developed to reduce the likelihood of cardiotoxicity without compromising efficacy and is currently conditionally approved for use as monotherapy in patients with multiply-relapsed or refractory aggressive B cell NHL. The use of pixantrone in combination therapy, often to replace doxorubicin or mitoxantrone, has or is currently being investigated in numerous studies in patients with aggressive or indolent NHL and is the focus of this review. These include the R-CPOP regimen (rituximab, cyclophosphamide, pixantrone, vincristine, prednisone) for aggressive NHL in the first-line setting, including a study in elderly patients with limited cardiac function, and for patients with relapsed NHL with prior anthracycline exposure; the PSHAP regimen (pixantrone, cytarabine, prednisone, cisplatin), also in the latter setting; the PREBen/PEBen regimen (pixantrone, bendamustine and etoposide with or without rituximab) as salvage therapy; and pixantrone in combination with fludarabine, dexamethasone, and rituximab (FPD-R) for relapsed indolent NHL.
  • Remitz, A.; De Pita, O.; Mota, A.; Serra-Baldrich, E.; Vakirlis, E.; Kapp, A. (2018)
    Background Atopic dermatitis (AD) is a common inflammatory skin disease in both adults and children. Whilst topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, have proven efficacy for the treatment of AD, it is important to involve experts to obtain their opinion on its optimal treatment. Objective Methods Using a modified Delphi approach, this project aimed to generate consensus amongst experts on the use of TCIs in the treatment of AD, with a focus on the differentiation between tacrolimus and pimecrolimus. Six expert dermatologists from different European countries participated in this project based on their experience with AD and its treatment, which was evaluated by literature analysis and expert opinion. Consensus amongst the experts was generated using a modified Delphi approach, consisting of three distinct phases, during which a web meeting (June 2017), two online rounds of blinded Delphi voting (July-September 2017) and a face-to-face meeting (November 2017) were conducted. The consensus statements concerned two main topics: (i) Background of AD; and (ii) TCIs in AD. Hot topics in the treatment of AD not supported by meta-analysis, clinical trials or large observational studies were also discussed based on clinical experience. Results Conclusion In total, 25 consensus statements were defined and validated: eight statements on the general background of AD and 17 statements on the use of TCIs in AD, including their mechanism of action and therapeutic indications in AD, efficacy in adult and paediatric AD patients, pharmacokinetics, incidence of adverse events and safety concerns. Hot topics on the use of TCIs for the treatment of AD included cream vs. ointment, dosages, TCIs contact allergy, burning sensation management, superinfection and vaccination concerns. Topical calcineurin inhibitors are a suitable therapy for AD, and selection of the specific TCI should be based on factors which differentiate tacrolimus from pimecrolimus.
  • Roos, Johan H.; Mäkitie, Antti A.; Tarkkanen, Jussi; Ilmarinen, Taru T. (2022)
    Background Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common. Methods This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival. Results The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS. Conclusions Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.
  • Canaani, Jonathan; Labopin, Myriam; Itälä-Remes, Maija; Blaise, Didier; Socie, Gerard; Forcade, Edouard; Maertens, Johan; Wu, Depei; Malladi, Ram; Cornelissen, Jan J.; Huynh, Anne; Bourhis, Jean Henri; Esteve, Jordi; Mohty, Mohamad; Nagler, Arnon (2019)
    Baseline cytogenetic studies at diagnosis remain the single most important determinant of outcome in patients with acute myeloid leukemia (AML). However, the prognostic role of the complete gamut of cytogenetic aberrations in AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently undefined. In addition, their significance in conjunction with FLT3-ITD status has not been addressed thus far. Using the ALWP/EBMT registry we conducted a retrospective analysis to determine the clinical outcomes of AML patients undergoing allo-HSCT with respect to specific recurring cytogenetic abnormalities complemented with FLT3-ITD status. We analyzed a cohort consisting of 8558 adult AML patients who underwent allo-HSCT from either a matched sibling or a matched unrelated donor. Patients with inv(3)(q21q26)/t(3;3)(q21;q26), del(5q), monosomy 7, chromosome 17p abnormalities, t(10;11)(p11-14;q13-23), t(6;11)(q27;q23), as well as those patients with a monosomal or complex karyotype experienced significantly inferior leukemia-free survival (LFS) compared to patients with a normal karyotype. Trisomy 14, del(9q), and loss of chromosome X were associated with improved LFS rates. A novel prognostic model delineating 5 distinct groups incorporating cytogenetic complexity and FLT3-ITD status was constructed with significant prognostic implications. Our analysis supports the added prognostic significance of FLT3-ITD to baseline cytogenetics in patients undergoing allo-HSCT.
  • Bersano, Anna; Guey, Stephanie; Bedini, Gloria; Nava, Sara; Herve, Dominique; Vajkoczy, Peter; Tatlisumak, Turgut; Saarela, Marika; van der Zwan, Albert; Klijn, Catharina J. M.; Braun, Kees P. J.; Kronenburg, Annick; Acerbi, Francesco; Brown, Martin M.; Calviere, Lionel; Cordonnier, Charlotte; Henon, Hilde; Thines, Laurent; Khan, Nadia; Czabanka, M.; Kraemer, Markus; Simister, Robert; Prontera, Paolo; Tournier-Lasserve, E.; Parati, Eugenio; European Moyamoya Dis Initiative (2016)
    Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions. (C) 2016 S. Karger AG, Basel
  • Kyrklund, Kristiina; Taskinen, Seppo; Rintala, Risto J.; Pakarinen, Mikko P. (2016)
    Purpose: Sexual dysfunction and impaired quality of life due to fecal incontinence are common after classic operations for anorectal malformations. We hypothesized that modern repairs may result in improved outcomes. Materials and Methods: Following ethical approval for this single institution cross-sectional study, all patients 16 years or older treated for rectourethral, vestibular or perineal fistula from 1983 onward were sent detailed postal questionnaires on sexual function and quality of life. Each respondent was age and gender matched to 3 controls randomly selected from the general population. Penoscrotal/gynecologic abnormalities were obtained from the records. Results: A total of 41 patients (62%) with a median age of 22 years participated in the study. Of the patients 20 were males with rectourethral fistula (prostatic in 60%), 10 were females with vestibular/perineal fistula and 11 were males with low malformations. Although experience of sexual relationships and orgasmic function were reported in comparable proportions to controls, age at coital debut was significantly delayed in all groups of patients (p Conclusions: While erectile and orgasmic function appear preserved after sagittal repair, further evaluation of fertility issues in males with rectourethral fistula is indicated. Larger multicenter studies are needed to confirm our findings.
  • Stefanovic, Vedran (2019)
    Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Eculizumab, the humanized monoclonal IgG2/4-antibody targeting C5 was approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of two rare diseases: PNH in 2007 and aHUS in 2011. There is an increasing number of publications of successful use of eculizumab for off-label indications, e.g., in pregnant women with antiphospholipid syndrome, sickle-cell anemia, and HELLP syndrome. These severe diseases are associated with both high maternal and fetal morbidity and mortality rate and substantial prematurity. Eculizumab has considerably improved overall outcome of patients with PNH and aHUS, enabling safe pregnancy for many women. Prolongation of pregnancy and the use of eculizumab, even for only a few weeks, may protect not only maternal renal function, but also alleviate acute and long-term renal consequences of prematurity in offspring.
  • Biancari, Fausto; Dalen, Magnus; Perrotti, Andrea; Fiore, Antonio; Reichart, Daniel; Khodabandeh, Sorosh; Gulbins, Helmut; Zipfel, Svante; Al Shakaki, Mosab; Welp, Henryk; Vezzani, Antonella; Gherli, Tiziano; Lommi, Jaakko; Juvonen, Tatu; Svenarud, Peter; Chocron, Sidney; Verhoye, Jean-Philippe; Bounader, Karl; Gatti, Giuseppe; Gabrielli, Marco; Saccocci, Matteo; Kinnunen, Eeva-Maija; Onorati, Francesco; Santarpino, Giuseppe; Alkhamees, Khalid; Ruggieri, Vito G.; Dell'Aquila, Angelo M. (2017)
    Background: The evidence of the benefits of using venoarterial extracorporeal membrane oxygenation (VA-ECMO) after coronary artery bypass grafting (CABG) is scarce. Methods: We analyzed the outcomes of patients who received VA-ECMO therapy due to cardiac or respiratory failure after isolated CABG in 12 centers between 2005 and 2016. Patients treated preoperatively with ECMO were excluded from this study. Results: VA-ECMO was employed in 148 patients after CABG for median of 5.0 days (mean, 6.4, SD 5.6 days). Inhospital mortality was 64.2%. Pooled in-hospital mortality was 65.9% without significant heterogeneity between the centers (I-2 8.6%). The proportion of VA-ECMO in each center did not affect in-hospital mortality (p = 0.861). No patients underwent heart transplantation and six patients received a left ventricular assist device. Logistic regression showed that creatinine clearance (p = 0.004, OR 0.98, 95% CI 0.97-0.99), pulmonary disease (p = 0.018, OR 4.42, 95% CI 1.29-15.15) and pre-VA-ECMO blood lactate (p = 0.015, OR 1.10, 95% CI 1.02-1.18) were independent baseline predictors of in-hospital mortality. One-, 2-, and 3-year survival was 31.0%, 27.9%, and 26.1%, respectively. Conclusions: One third of patients with need for VA-ECMO after CABG survive to discharge. In view of the burden of resources associated with VA-ECMO treatment and the limited number of patients surviving to discharge, further studies are needed to identify patients who may benefit the most from this treatment. (C) 2017 Elsevier B.V. All rights reserved.
  • Vettenranta, Kim; Dobsinska, Veronika; Kertesz, Gabriella; Svec, Peter; Buechner, Jochen; Schultz, Kirk R. (2022)
    Previously, the outcome of paediatric Philadelphia-chromosome-positive (Ph+) ALL treated with conventional chemotherapy alone was poor, necessitating the use of haematopoietic stem cell transplantation (HSCT) for the best outcomes. The recent addition of tyrosine kinase inhibitors (TKIs) alongside the chemotherapy regimens for Ph+ ALL has markedly improved outcomes, replacing the need for HSCT for lower risk patients. An additional poor prognosis group of Philadelphia-chromosome-like (Ph-like) ALL has also been identified. This group also can be targeted by TKIs in combination with chemotherapy, but the role of HSCT in this population is not clear. The impact of novel targeted immunotherapies (chimeric antigen receptor T cells and bispecific or drug-conjugated antibodies) has improved the outcome of patients, in combination with chemotherapy, and made the role of HSCT as the optimal curative therapy for Ph+ ALL and Ph-like ALL less clear. The prognosis of patients with Ph+ ALL and persistent minimal residual disease (MRD) at the end of consolidation despite TKI therapy or with additional genetic risk factors remains inferior when HSCT is not used. For such high-risk patients, HSCT using total-body-irradiation-containing conditioning is currently recommended. This review aims to provide an update on the current and future role of HSCT for Ph+ ALL and addresses key questions related to the management of these patients, including the role of HSCT in first complete remission, MRD evaluation and related actions post HSCT, TKI usage post HSCT, and the putative role of HSCT in Ph-like ALL.