Parálisis facial alternobárica: a propósito de un caso y revisión de la literatura / Alternobaric facial palsy: case report and literature review

La parálisis o paresia facial alternobárica es una neuropraxia del séptimo nervio cra-neal debido a cambios de presión. Se produce en el contexto de una disfunción de la trompa de Eustaquio, una dehiscencia canal del nervio facial y cambios en la presión atmosférica. Se considera una rara complicación de barotrauma. Su prevalencia es difícil de estimar y, probablemente, se encuentre subreportada. La forma de presentación más habitual incluye paresia facial, plenitud aural, hipoacusia, otalgia, parestesias faciales y linguales. La mayoría de los episodios son transitorios, con una duración entre minutos y algunas horas, con recuperación posterior completa. Entre los diagnósticos diferenciales se encuentran causas periféricas y centrales de paresia facial, las cuales hay que sospechar ante la persistencia de los síntomas en el tiempo o ante la presencia de otros signos o síntomas neurológicos. La evaluación inicial debe incluir un examen otoneurológico completo. La tomografía computarizada de hueso temporal favorece la visualización de posibles dehiscencias del canal del facial. La prevención de nuevos episodios incluye la práctica de ecualización efectiva, la resolución de la disfunción de la trompa de Eustaquio y en algunos casos específicos, métodos alternativos de ventilación del oído medio como la colocación de tubos de ventilación. Una vez instalada la parálisis facial, si no se produce recuperación espontánea, el uso de corticoides es una opción. Se presenta un caso de paresia facial alternobárica recurrente y una revisión de literatura.

Alternobaric facial palsy or paralysis is a neuropraxia of the seventh cranial nerve due to pressure changes. It occurs in the context of Eustachian tube dysfunction, facial nerve canal dehiscence, and changes in atmospheric pressure. It is considered a rare complication of barotrauma. Its prevalence is difficult to estimated, and this condition is probably underreported. The most common form of presentation includes facial weakness, ear fullness or pressure, hearing loss, otalgia, facial and lingual paresthesias. Most episodes are transient, lasting from minutes to a few hours, with a subsequent complete recovery. Among the possible differential diagnoses are peripheral and central causes of facial paralysis, which must be suspected due to the persistence of symptoms over time or the presence of other neurological signs or symptoms. The initial evaluation should include a complete otoneurological examination. Computed tomography of the temporal bone is useful for the visualization of facial canal dehiscence. Prevention of further episodes includes practicing effective equalization, Eustachian tube dysfunction treatment, and in certain specific cases, alternative middle ear ventilation methods such as tympanostomy tubes. Once facial paralysis is established, if spontaneous recovery does not occur, the use of corticosteroids is considered an option. A case of recurrent alternobaric facial paresis and a review of the literature are presented.

Unexpected mould diversity in clinical isolates from French Guiana and associated identification difficulties.

New mold species are increasingly reported in invasive fungal infections. However, these fungi are often misdiagnosed or undiagnosed due to the use of inappropriate laboratory diagnostic tools. Tropical countries, such as French Guiana, harbor a vast diversity of environmental fungi representing a potential source of emerging pathogens. To assess the impact of this diversity on the accuracy of mold-infection diagnoses, we identified mold clinical isolates in French Guiana during a five-month follow-up using both microscopy and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. In total, 38.8% of the 98 obtained molds isolates could not be identified and required a DNA-based identification. Fungal diversity was high, including 46 species, 26 genera, and 13 orders. Fungal ecology was unusual, as Aspergillus species accounted for only 27% of all isolates, and the Nigri section was the most abundant out of the six detected Aspergillus sections. Macromycetes (orders Agaricales, Polyporales, and Russulales) and endophytic fungi accounted for respectively 11% and 14% of all isolates. Thus, in tropical areas with high fungal diversity, such as French Guiana, routine mold identification tools are inadequate. Molecular identifications, as well as morphological descriptions, are necessary for the construction of region-specific mass spectrum databases. These advances will improve the diagnosis and clinical management of new fungal infections. LAY SUMMARY: In French Guiana, environmental fungal diversity may be a source of emerging pathogens. We evaluated microscopy and mass spectrometry to identify mold clinical isolates. With 39% of unidentified isolates, a region-specific mass spectrum database would improve the diagnosis of new fungal infections.

[Assessment of Asbestos-related Occupational Diseases: Socio-medical and Legal Aspects]. / Sozialmedizinische und sozialjuristische Aspekte in der Zusammenhangsbegutachtung asbestbedingter Berufskrankheiten.

Occupational diseases are certain diseases designated as such by law. Whereas the medical conditions are described in guidelines, their recognition is based on judicial administrative procedures. Establishing causality is based on requirements of social law. The basic socio-legal concepts are mentioned and the principles of causality in asbestos-related occupational diseases are listed. Exemplary social court judgments are cited. Judgements may not infrequently differ from the medical point of view. The aim of this article is to describe the correct use of social medical understanding in order to carry out adequate assessment of occupational diseases, which implements the legal requirements.

Bortezomib and Vorinostat Therapy as Maintenance Therapy after Autologous Transplant for Multiple Myeloma.

BACKGROUND: In multiple myeloma (MM), relapse is a frequent complication after autologous hematopoietic stem cell transplant (ASCT). To reduce the risk of relapse, additional therapy has been added post-ASCT. In a nontransplant relapse setting, the combination of intravenous bortezomib and oral vorinostat (BV) was studied and showed efficacy. Therefore, it was reasonable to study this combination therapy post-ASCT. PATIENTS AND METHODS: We report on BV given post-ASCT. All 30 patients underwent conditioning for ASCT with high-dose melphalan. After recovery from the acute transplant-related toxicity, BV therapy was started and given for a total of 12 (28-day) cycles. RESULTS: The most common toxicities were hematological, gastrointestinal (diarrhea and nausea), fatigue, and peripheral neuropathy. The median follow-up for BV patients is 7.8 (range: 6.12-9.03) years. After BV therapy, 18 patients (60%) are alive, and 9 (30%) are alive without disease progression. CONCLUSIONS: BV can be given post-ASCT with an acceptable toxicity profile and produces reasonable disease-free and overall survival rates. A randomized study comparing the BV regimen to single-agent lenalidomide or bortezomib is needed.

Factors influencing the clinical outcome of preimplantation genetic testing for polycystic kidney disease.

STUDY QUESTION: What are the factors influencing the success rate for couples undergoing preimplantation genetic testing (PGT) for polycystic kidney disease (PKD)? SUMMARY ANSWER: In our study cohort, the live birth delivery rate is significantly associated with female age while the male infertility accompanying autosomal dominant PKD (ADPKD) does not substantially affect the clinical outcome. WHAT IS KNOWN ALREADY: While women with ADPKD have no specific fertility problems, male ADPKD patients may present with reproductive system abnormalities and infertility. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study involves 91 PGT cycles for PKD for 43 couples (33 couples for PKD1, 2 couples for PKD2 and 8 couples for autosomal recessive PKD (ARPKD)) from January 2005 until December 2016 with follow-up of transfers until end of 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixteen single-cell clinical tests for PKD based on multiplex PCR of short tandem repeat markers, with or without a specific mutation were developed and applied for diagnosis of 584 Day 3 cleavage stage embryos. In 18 couples, the male partner was affected with ADPKD (=Group A) and 12 of them had a documented infertility status. Group A underwent 52 cycles to oocyte retrieval. For 18 other couples, the female partner was affected with ADPKD (=Group B) and four male partners from this group had a documented history of infertility. This group underwent 31 cycles to OR. MAIN RESULTS AND THE ROLE OF CHANCE: Genetic analysis resulted in 545 embryos (93.3%) with a diagnosis, of which 215 (36.8%) were genetically transferable. Transfer of 74 embryos in 53 fresh cycles and of 34 cryopreserved embryos in 33 frozen-warmed embryo transfer cycles resulted in a live birth delivery rate of 38.4% per transfer with 31 singleton live births, two twin live births and one ongoing pregnancy. The observed cumulative delivery rate was 57.8% per couple after five treatment cycles. Thirty cryopreserved embryos still remain available for transfer. The clinical pregnancy rate per transfer (fresh + frozen; 45.9% in group A versus 60.0% in group B, P < 0.05) and the live birth delivery rate per transfer (fresh + frozen; 27.0% in group A versus 42.9% in group B, P < 0.05) was significantly lower for couples with the male partner affected with ADPKD compared with couples with the female partner affected with ADPKD. However, a multivariate logistic regression analysis showed that only female age was associated with live birth delivery rate (odds ratio = 0.87; 95% CI: 0.77-0.99; P = 0.032). LIMITATIONS, REASONS FOR CAUTION: This study is based on retrospective data from a single centre with Day 3 one-cell and two-cell biopsy. Further analysis of a larger cohort of PKD patients undergoing PGT is required to determine the impact of male infertility associated with ADPKD on the cumulative results. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about factors affecting the clinical outcome after PGT can be a valuable tool for physicians to counsel PKD patients about their reproductive options. Males affected with ADPKD who suffer from infertility should be advised to seek treatment in time to improve their chances of conceiving a child. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Repository corticotrophin injection exerts direct acute effects on human B cell gene expression distinct from the actions of glucocorticoids.

Repository corticotrophin injection (RCI, H.P Acthar® gel) has been approved for use in the management of multiple autoimmune and inflammatory diseases for more than a half-century, but its mechanism of action is not well understood. We used RNA-Seq methods to define RCI-regulated mRNAs in cultured human B cells under conditions of activation by interleukin (IL)-4 and CD40 ligand. Following IL-4/CD40L activation and RCI treatment we found up-regulation of 115 unique mRNA transcripts and down-regulation of 80 unique mRNAs. The effect on these RNA levels was dose-dependent for RCI and was distinct from changes in mRNA expression induced by treatment with a potent synthetic glucocorticoid. RCI down-regulated mRNAs were observed to include a significant over-representation of genes critical for B cell proliferation under activating conditions. These data confirm that RCI exerts direct effects on human B cells to modulate mRNA expression in specific pathways of importance to B cell function and that, at the molecular level, the effects of RCI are distinct from those exerted by glucocorticoids.

Spectrum of mutations in cystinuria patients presenting with prenatal hyperechoic colon.

Cystinuria is a heterogeneous, rare but important cause of inherited kidney stone disease due to mutations in 2 genes: SLC3A1 and SLC7A9. Antenatal hyperechoic colon (HEC) has been reported in some patients as a non-pathological consequence of the intestinal transport defect. We report 83 patients affected by cystinuria: 44 presented prenatally with a HEC (HEC group) and 39 with a classical postnatal form (CC group). SLC3A1 and SLC7A9 were sequenced. All patients were fully genotyped, and the relationship between the genotype and clinical features was analyzed. We identified mutations in SLC3A1 in 80% of the HEC group and in only 49% of the CC group. The SLC3A1 p.Thr216Met mutation was found in 21% of the alleles in the HEC group but was never found in the CC group. Most of the mutations found in the HEC group were considered severe mutations in contrast with the CC group. Twenty-five novel mutations were reported. This study shows a relationship between genotype and the clinical form of cystinuria, suggesting that only the patients with the most severe mutations presented with an HEC. These results emphasized the need for prenatal cystinuria screening using classical third-trimester ultrasound scan and the early management of suspected newborns.

Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study.

DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 (range: 19-72) years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well tolerated. As response rates appeared similar with 7 and 10 days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D). Among 46 patients treated at/above the RP2D, 10 (22%) achieved a complete remission (CR), 8 without measurable residual disease; five additional patients achieved CR with incomplete platelet recovery, for an overall response rate of 33%. Seven patients (15%) died within 28 days of treatment initiation. Infection/neutropenic fever, nausea and mucositis were the most common adverse events. While the CR rate compared favorably to a matched historic control population (observed/expected CR ratio=1.77), CR rate and survival were similar to two contemporary salvage regimens used at our institution (G-CLAC (granulocyte colony-stimulating factor (G-CSF); clofarabine; cytarabine) and G-CLAM (G-CSF; cladribine; cytarabine; mitoxantrone)). Thus, while meeting the prespecified efficacy goal, we found no evidence that dec/MEC is substantially better than other cytarabine-based regimens currently used for relapsed/refractory AML.

Characterization of the novel HLA-B*49:39 allele identified in a German leukaemia patient.

HLA-B*49:39 allele is characterised by 1 amino acid substitution in the alpha 1 domain.

A multicenter trial of myeloablative clofarabine and busulfan conditioning for relapsed or primary induction failure AML not in remission at the time of allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic cell transplantation (HCT) may produce long-term survival in AML after relapse or primary induction failure (PIF). However, outcomes of HCT performed for AML not in remission are historically poor given high relapse rates and transplant-related mortality. Preliminary studies suggest conditioning with clofarabine and myeloablative busulfan (CloBu4) may exert significant anti-leukemic effects without excessive toxicity in refractory hematologic malignancies. A prospective multicenter phase II trial was conducted to determine the efficacy of CloBu4 for patients proceeding directly to HCT with AML not in remission. Seventy-one patients (median age: 56 years) received CloBu4. At day 30 after HCT, 90% achieved morphologic remission. The incidence of non-relapse mortality and relapse at 2 years was 25% and 55%, respectively. The 2-year overall survival (OS) and event-free survival (EFS) were 26% and 20%, respectively. Patients entering HCT in PIF had significantly greater EFS than those in relapse (34% vs 8%; P<0.01). Multivariate analysis comparing CloBu4 with a contemporaneous cohort (Center for International Blood and Marrow Transplantation Research) of AML not in remission receiving other myeloablative conditioning (n=105) demonstrated similar OS (HR: 1.33, 95% confidence interval: 0.92-1.92; P=0.12). HCT with myeloablative CloBu4 is associated with high early response rates and may produce durable remissions in select patients with AML not in remission.

The novel HLA-C*15:103 is characterised by an amino acid substitution in the alpha 2 domain.

HLA-C*15:103 allele is characterised by one amino acid substitution in the alpha 2 domain.

A randomized study of melphalan 200 mg/m(2) vs 280 mg/m(2) as a preparative regimen for patients with multiple myeloma undergoing auto-SCT.

We aimed to examine whether doses of melphalan higher than 200 mg/m(2) improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m(2) (mel200) vs 280 mg/m(2) (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (⩾nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, ⩾nCR 22 vs 39%, P=0.03, ⩾PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR)=1.15 (95% confidence interval (CI), 0.62-2.13, P=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52-1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen-related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies.

Humanized Mice as Preclinical Models in Transplantation.

Animal models have been instrumental in our understanding of the mechanisms of rejection and the testing of novel treatment options in the context of transplantation. We have now entered an exciting era with research on humanized mice driving advances in translational studies and in our understanding of the function of human cells in response to pathogens and cancer as well as the recognition of human allogeneic tissues in vivo. In this chapter we provide a historical overview of humanized mouse models of transplantation to date, outlining the distinct strains and share our experiences in the study of human transplantation immunology.

Gastroschisis in a developing country: poor resuscitation is a more significant predictor of mortality than postnasal transfer time.

BACKGROUND: The time from birth to the first paediatric surgical consultation of neonates with gastroschisis is a predictor of mortality in dveloping countries. This is contrary to findings in the developed world. We set out to document this relationship within our population. METHOD: Neonates with gastroschisis who were transferred to Steve Biko Academic Hospital within the study period were included. The association between mortality and demographic, clinical and biochemical variables was assessed. Significant variables after univariate analysis were subjected to multivariates regression. RESULTS: Sixty patients were included. The mortality rate was 65%. Mean transfer time and distance were 14.9 hours and 225km. Forty-eight per cent of the neonates were either dehydrated or in hypovolaemic shock clinically on arrival. Eight neonates arrived hypothermic. It was shown through univariate analysis that female sex, appropriate weight for gestational age, hydration status, gestation, transfer time, serum urea, base deficit and serum bicarbonate (HCO3) were significant predictors of mortality. Only female sex, appropriate weight for gestational age and serum HC03 were shown to be significant using ultivariate analysis. CONCLUSION: Our high mortality rate was not due to lengthy transfer times. The poor clinical condition of the patients on arrival at our hospital, which relates to deficiencies in the neonatal transfer system, had a direct impact on the survival of neonates with gastroschisis.

Mesenchymal stromal cells derived from acute myeloid leukemia bone marrow exhibit aberrant cytogenetics and cytokine elaboration.

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) play a fundamental role in the BM microenvironment (BME) and abnormalities of these cells may contribute to acute myeloid leukemia (AML) pathogenesis. The aim of the study was to characterize the cytokine and gene expression profile, immunophenotype and cytogenetics of BM-MSCs from AML patients compared to normal BM-MSCs from healthy donors. AML BM-MSCs showed decreased monocyte chemoattractant protein-1 levels compared to normal BM-MSCs. AML BM-MSCs expressed similar ß1 integrin, CD44, CD73, CD90 and E-cadherin compared to normal BM-MSCs. Cytogenetic analysis revealed chromosomal aberrations in AML BM-MSCs, some overlapping with and others distinct from their corresponding AML blasts. No significant difference in gene expression was detected between AML BM-MSCs compared to normal BM-MSCs; however, comparing the differences between AML and MSCs from AML patients with the differences between normal hematopoietic cells and normal MSCs by Ingenuity pathway analysis showed key distinctions of the AML setting: (1) upstream gene regulation by transforming growth factor beta 1, tumor necrosis factor, tissue transglutaminase 2, CCAAT/enhancer binding protein alpha and SWItch/Sucrose NonFermentable related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; (2) integrin and interleukin 8 signaling as overrepresented canonical pathways; and (3) upregulation of transcription factors FBJ murine osteosarcoma viral oncogene homolog and v-myb avian myeloblastosis viral oncogene homolog. Thus, phenotypic abnormalities of AML BM-MSCs highlight a dysfunctional BME that may impact AML survival and proliferation.

Utilization of stored autologous PBSCs to support second autologous transplantation in multiple myeloma patients in the era of novel agent therapy.

Outcomes in multiple myeloma (MM) have improved significantly with novel agent therapy and autologous stem cell transplantation (ASCT). ASCTs are typically planned as either tandem or a single transplant with additional stored PBSCs available for a second salvage transplant. To accommodate these strategies, many centers routinely collect and store adequate PBSCs for two ASCTs. We analyzed the cost associated with this practice by determining the expenses of PBSC collection, cryopreservation and storage, and the ultimate use of additional cryopreserved PBSCs in patients who had undergone at least one ASCT. There were 889 MM patients transplanted between 1993 and 2011 at our center. Most (N=726) had residual PBSCs in storage after their first ASCT (ASCT1). Only 135 patients underwent a second ASCT within a median of 14 months after ASCT1. The percentage of patients receiving a second ASCT declined over time. The resources required to collect and store unused PBSCs added up to 336 extra patient days of apheresis and 41 587 extra patient months of cryopreservation, translating into an average extra cost per patient of US$4981.12. A reconsideration of conventional PBSC collection and storage practices would save significant cost for the majority of MM patients who never undergo a second ASCT.