Laparoscopic sleeve gastrectomy in a patient with situs inversus totalis and Kartagener syndrome: an unusual surgical conundrum.

Kartagener syndrome is a rare autosomal recessive condition. Approximately 25% of those with situs inversus totalis suffer the syndrome. With the rising overall number and indications for bariatric surgery, this condition will be increasingly recognised. We present a case of a 25-year-old woman with SIT and Kartagener syndrome who underwent a laparoscopic sleeve gastrectomy. As with all bariatric surgery, a multidisciplinary team approach was important in managing such a case. There were considerable cognitive challenges for the surgical team both preoperatively and during the procedure. The patient tolerated the operation well and was discharged 2 days after the surgery. At 12-months follow-up, the patient had achieved 125% excess weight loss. This case illustrates that an experienced surgeon can safely perform a laparoscopic sleeve gastrectomy on a patient with situs inversus totalis.

Tratamiento de la discinecia ciliar primaria / Treatmen of ciliary primary discinesia

At present, there is no specific treatment for primary ciliary dyskinesia, nor controlled and randomized clinical trials to determine how the management and monitoring of these patients should be considered. The therapeutic options are extrapolated from other diseases, such as cystic fibrosis, or non-cystic fibrosis bronchiectasis. However, the implementation of specific groups of experts, both in the USA (PDC-foundation) and in Europe (BESTCILIA or BEAT-PD), are helping to increase knowledge of the disease, opening research channels and seeking new treatments. Until we have therapies capable of correcting the basic defect of the disease, the pillars of treatment are the daily cleansing of the airways and aggressive antibiotherapy against respiratory infections. Multidisciplinary care in specialized centers where pulmonary function is monitored and the infection is prevented and treated will improve, as in cystic fibrosis, the results of patients.

En la actualidad no existe un tratamiento específico para la discinesia ciliar primaria, ni se cuenta con ensayos clínicos controlados y randomizados que permitan determinar cómo debe plantearse el manejo y seguimiento de estos pacientes. Las opciones terapéuticas son extrapoladas de otras enfermedades, como la fibrosis quística, o las bronquiectasias no fibrosis quística. Sin embargo, la puesta en marcha de grupos específicos de expertos, tanto en USA (PDC-foundation) como en Europa (BESTCILIA o BEAT-PD), están permitiendo incrementar el conocimiento de la enfermedad, abriendo vías de investigación y buscando nuevos tratamientos. Hasta contar con terapias capaces de corregir el defecto básico de la enfermedad, los pilares del tratamiento son la limpieza diaria de las vías aéreas y la antibioterapia agresiva frente a las infecciones respiratorias. La atención multidisciplinar en centros especializados donde se monitorice la función pulmonar y se prevengan y traten las infecciones mejorará, como en la fibrosis quística, los resultados de los pacientes.

Imágenes diagnósticas en el estudio del compromiso pulmonar de la discinesia ciliar primaria en niños / Chest imaging in study of primary ciliary dyskinesia in children

The diagnosis of primary ciliary dyskinesia (PCD) is complex and requires high clinical suspicion. The findings in the diagnostic images are nonspecific and can be seen in other conditions of the airway. In this review, we will describe the findings of PCD in chest radiography and computed tomography, with emphasis on some of the characteristics that differentiate it from cystic fibrosis and we will review the role of CT in the monitoring of changes of the PCD, since the CT findings correlate very well with the structural changes that occur in the course of PCD, especially bronchiectasis. However, using serial CTs should be decided on a case-by-case basis to avoid unnecessary radiation because they are pediatric patients.

El diagnóstico de la Discinesia ciliar primaria (DCP) es complejo y requiere alta sospecha clínica. Los hallazgos en la imágenes diagnósticas son inespecíficos y se pueden ver en otras afecciones de la vía aérea. En esta revisión describiremos los hallazgos de la DCP en Radiología simple y en Tomografía computada (TC), con énfasis en algunas de las características que permiten diferenciarla de la Fibrosis quística (FQ) y revisaremos el rol de la TC en la monitorización de la DCP ya que los hallazgos en la TC se correlacionan muy bien con los cambios estructurales que ocurren en el curso de la DCP, en especial las bronquiectasias. Sin embargo usar TC seriadas se debe decidir caso por caso para evitar la radiación innecesaria por ser pacientes pediátricos.

[Kartagener syndrome: neonatal diagnosis. A case report]. / Síndrome de Kartagener: diagnóstico neonatal. A propósito de un caso.

Kartagener Syndrome is an inherited autosomal recessive disorder characterized by primary ciliary dyskinesia and the triad of situs inversus viscerum, chronic sinus disease and bronchiectasis. Its prevalence varies from 1/15 000 to 1/30 000 but it is estimated that a lot of patients with primary ciliary dyskinesia have not been diagnosed as such. Its clinical presentation is non-specific and heterogeneous, and there is not a single, gold standard, diagnostic test. The diagnosis is often delayed because of these reasons and limitations and no availability of diagnostic tests. Early diagnosis and treatment change patient's prognosis. In addition, Scientific Societies have published recent diagnostic algorithm to evaluate the patient with suspected primary ciliary dyskinesia. Therefore, it is important to keep up to date with all the latest articles. We present the case of a newborn with this syndrome diagnosed by genetic analysis in a secondary care hospital.

El síndrome de Kartagener es una enfermedad hereditaria autosómica recesiva caracterizada por la asociación de discinesia ciliar primaria y la tríada situs inversus total, sinusitis crónicas y bronquiectasias. Su prevalencia varía en 1/15 000-1/30 000, pero se estima que muchos pacientes con discinesia ciliar primaria no han sido diagnosticados. Su presentación clínica es inespecífica y heterogénea, y no hay una única prueba gold standard para su diagnóstico. Esto, unido a las limitaciones y no disponibilidad de las pruebas, hace que el diagnóstico se retrase. Un diagnóstico y tratamiento adecuados de forma precoz modifican el pronóstico. En los últimos años, las sociedades han publicado algoritmos diagnósticos para pacientes con clínica sugestiva. Por ello, es importante una puesta al día y enfatizar en la necesidad de una sospecha clínica ante las manifestaciones clínicas de esta enfermedad. Se presenta a un recién nacido con este síndrome diagnosticado por estudio genético en un hospital secundario.

Accuracy of High-Speed Video Analysis to Diagnose Primary Ciliary Dyskinesia.

BACKGROUND: Diagnosis of primary ciliary dyskinesia (PCD) relies on a combination of tests. High-speed video microscopy analysis (HSVA) is widely used to contribute to the diagnosis. It can be analyzed on the day of diagnostic consultation, but the qualitative analyses are subjective. Diagnostic accuracy and reliability of assessing ciliary function have not been robustly evaluated. We aimed to establish the accuracy of HSVA to diagnose PCD compared with a combination of tests, and to assess the interobserver reliability of HSVA analysis. METHODS: We randomly selected and anonymized archived videos from 120 patients seen at three UK PCD centers. Three experienced scientists independently reviewed six videos per patient, using a standardized proforma, blinded to diagnostic and clinical data. We compared study outcomes with two references: (1) a combination of diagnostic tests in accordance with the European Respiratory Society PCD diagnostic guidelines and (2) original clinical outcome determined by all available diagnostic tests. RESULTS: HSVA had excellent sensitivity and specificity to diagnose PCD: (1) 100% and 96%, respectively, compared with ERS guidelines, and (2) 96% and 91% compared with diagnostic outcomes. There was high interobserver agreement for "PCD-positive" outcomes (κ = 0.7). CONCLUSIONS: Specialist scientists accurately diagnosed PCD using HSVA, with high interobserver agreement. HSVA can be reliably used to counsel patients and commence treatment on the day of testing while awaiting confirmatory investigations.

Primary Ciliary Dyskinesia: Longitudinal Study of Lung Disease by Ultrastructure Defect and Genotype.

RATIONALE: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood. OBJECTIVES: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype. METHODS: This was a prospective, longitudinal (5 yr), multicenter, observational study. Inclusion criteria were less than 19 years at enrollment and greater than or equal to two annual study visits. Linear mixed effects models including random slope and random intercept were used to evaluate longitudinal associations between the ciliary defect group (or genotype group) and clinical features (percent predicted FEV1 and weight and height z-scores). MEASUREMENTS AND MAIN RESULTS: A total of 137 participants completed 732 visits. The group with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) (n = 41) were significantly younger at diagnosis and in mixed effects models had significantly lower percent predicted FEV1 and weight and height z-scores than the isolated outer dynein arm defect (n = 55) group. Participants with CCDC39 or CCDC40 mutations (n = 34) had lower percent predicted FEV1 and weight and height z-scores than those with DNAH5 mutations (n = 36). For the entire cohort, percent predicted FEV1 decline was heterogeneous with a mean (SE) decline of 0.57 (0.25) percent predicted/yr. Rate of decline was different from zero only in the IDA/MTD/CA group (mean [SE], -1.11 [0.48] percent predicted/yr; P = 0.02). CONCLUSIONS: Participants with IDA/MTD/CA defects, which included individuals with CCDC39 or CCDC40 mutations, had worse lung function and growth indices compared with those with outer dynein arm defects and DNAH5 mutations, respectively. The only group with a significant lung function decline over time were participants with IDA/MTD/CA defects.

Automated computed tomographic scoring of lung disease in adults with primary ciliary dyskinesia.

BACKGROUND: The present study aimed to develop an automated computed tomography (CT) score based on the CT quantification of high-attenuating lung structures, in order to provide a quantitative assessment of lung structural abnormalities in patients with Primary Ciliary Dyskinesia (PCD). METHODS: Adult (≥18 years) PCD patients who underwent both chest CT and spirometry within a 6-month period were retrospectively included. Commercially available lung segmentation software was used to isolate the lungs from the mediastinum and chest wall and obtain histograms of lung density. CT-density scores were calculated using fixed and adapted thresholds based on various combinations of histogram characteristics, such as mean lung density (MLD), skewness, and standard deviation (SD). Additionally, visual scoring using the Bhalla score was performed by 2 independent radiologists. Correlations between CT scores, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were evaluated. RESULTS: Sixty-two adult patients with PCD were included. Of all histogram characteristics, those showing good positive or negative correlations to both FEV1 and FVC were SD (R = - 0.63 and - 0.67; p < 0.001) and Skewness (R = 0.67 and 0.67; p < 0.001). Among all evaluated thresholds, the CT-density score based on MLD + 1SD provided the best negative correlation with both FEV1 (R = - 0.68; p < 0.001) and FVC (R = - 0.71; p < 0.001), close to the correlations of the visual score (R = - 0.60; p < 0.001 for FEV1 and R = - 0.62; p < 0.001, for FVC). CONCLUSIONS: Automated CT scoring of lung structural abnormalities lung in primary ciliary dyskinesia is feasible and may prove useful for evaluation of disease severity in the clinic and in clinical trials.

Never too old for an inherited condition.

Primary ciliary dyskinesia is an uncommon, inherited condition causing progressive suppurative airway lung disease with subsequent bronchiectasis, chronic rhinitis-sinusitis, deafness and reduced fertility. Diagnosis is often delayed by lack of awareness of the condition in the medical community and limited access to the few centres in Australia able to do full diagnostic testing. This report details the late diagnosis of primary ciliary dyskinesia in two adults who have had long-standing interactions with medical services but in whom the diagnosis was never considered or even dismissed. Greater awareness of the condition will reduce time to diagnosis, prevent administration of ineffective therapy and allow earlier institution of targeted therapy.

Síndrome de Kartagener, importancia de detectar la tríada diagnóstica característica / Kartagener syndrome, the importance of detecting the characteristic diagnostic triad

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Reduced anaerobic and aerobic performance in children with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) restricts lifestyle and increases morbidity. The aim of the study was to investigate anaerobic and aerobic performance in children with PCD and their healthy counterparts. Thirty-one children with PCD and 29 age- and sex-matched healthy subjects were studied. Pulmonary function, hand grip strength (HGS), quadriceps strength (QMS), physical activity, anaerobic capacity (muscle power sprint test), and aerobic performance (modified shuttle walk test (MSWT)) were determined. Pulmonary function, HGS, QMS, mean anaerobic power (MAP), and MSWT distance in PCD were significantly lower than those of healthy subjects (p < 0.05). In PCD, the MAP was significantly correlated with age, FEV1, and the mean kcal for 3 days (p < 0.05), and age was its independent predictor (p < 0.05). The MSWT distance was significantly related to gender and weight (p < 0.05), and gender was selected as its independent predictor (p < 0.05). In healthy controls, the MAP was significantly associated with age, gender, FVC, FEV1, HGS, QMS, and the mean kcal for three days (p < 0.05). The MSWT distance was significantly related to weight and body mass index in healthy group (p < 0.05). CONCLUSION: Anaerobic and aerobic performance is impaired in PCD from the early stages. Age determines anaerobic performance. Gender is the determinant of aerobic performance. Whether skeletal muscle characteristics and sex-related changes in body composition affect anaerobic and aerobic capacity in PCD children warrants further study. What is Known: • Exercise performance is determined by anaerobic and aerobic power. • Few studies have shown that PCD patients have lower aerobic performance which is associated with impaired lung function. What is New: • The present research indicated that both anaerobic and aerobic exercise capacity determined using field testing is impaired in PCD from the early stages. • Anaerobic capacity was found to be independently associated with age in PCD. Higher aerobic performance is independently associated with male gender.

[Cilia ultrastructural and gene variation of primary ciliary dyskinesia: report of three cases and literatures review].

Objective: To analyze the clinical manifestations, cilia ultrastructure and gene variations of primary ciliary dyskinesia (PCD). Methods: Analysis of three cases diagnosed as PCD by transmission electron microscopy of the endobronchial biopsy material in Division of Pediatric Pulmonology of Shandong Provincial Hospital between 2013 and 2016. Target gene sequence capture and next generation sequencing were used to analyze the gene. Related literatures on gene variation of PCD in Chinese were reviewed from Online Mendelian Inheritance in Man, Human Gene Mutation Database, PubMed and CNKI up to July 2017 by using search terms of "PCD" , "gene" , "Chinese". Results: There were one male and two females aged from 10 to 11 years. The common symptoms included recurrent respiratory infection, sinusitis and bronchiectasis. Two of them had situs inversus. Case 1 had lack of outer and inner dynein arms with compound heterozygous mutation of LRRC6. Case 2 had outer and inner dynein arms defects with heterozygous mutations of DNAH5 and DNAH11. Case 3 had abnormality in microtubule and inner dynein arms with homozygous mutation of CCDC39. All the variations mentioned above have not been reported before. Twelve cases have been reported about gene variations in PCD in Chinese from eight reports. All these patients had recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis. Nine of them had dextrocardia. Four cases have taken an effective nasal (or bronchial) mucosal biopsy. 1 case had inner and outer dynein arms defects. One case had inner dynein arms and radial spokes defects. One case had microtubule and central pair defects. And 1 case had normal cilia ultrastructure. Eight kinds of gene variations were found. Three cases had gene variations of DNAH5. 2 cases had gene variations of DYX1C1. 2 cases had gene variations of CCNO. There was 1 case with gene variations of CCDC39, CCDC40, HYDIN, ARMC4 and DNAI1 separately. Conclusions: Recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis are the common symptoms of PCD. Eleven of fifteen Chinese PCD patients with positive gene mutations were Kartagener syndrome. Cilia ultrastructure showed defects of inner and outer dynein arms, radial spokes, microtubule and central pair. Ten kinds of gene variations were found: DNAH5, DYX1C1, CCNO, CCDC39, CCDC40, HYDIN, ARMC4, DNAI1, LRRC6、DNAH11.

Gas exchanges in children with cystic fibrosis or primary ciliary dyskinesia: A retrospective study.

Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) both entail bronchiectasis and pulmonary impairment as measured using spirometry, during childhood. We aimed at looking whether blood gas exchanges progressed differently between CF and PCD children in a retrospective study of repeated measurements. Comparisons between groups (Wilcoxon-Mann-Whitney and Chi-squared tests) and a mixed linear model, adjusted for age, evaluated associations between diseases and PaO2, PaCO2, or PaO2-PaCO2 ratio. Among 42 PCD and 73 CF children, 62% and 59% had respectively bronchiectasis (P = 0.75). Spirometry and blood gases were similar at inclusion (PaO2 median [IQR] PCD -1.80 [-3.40; -0.40]; CF -1.80 [-4.20; 0.60] z-scores; P = 0.72). PaO2 and PaO2-PaCO2 ratio similarly and significantly decreased with age in both groups (P < 0.01) whereas PaCO2 increased more in CF (P = 0.02) remaining within the range of normal (except for one child). To conclude, gas exchange characteristics, similarly initially impaired in PCD and CF children, tended to less deteriorate with time in PCD children who could benefit from an early diagnosis.

Kartagener's syndrome: a case report.

BACKGROUND: Kartagener's syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive inherited disorder characterized by the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. Abnormal ciliary structure or function leading to impaired ciliary motility is the main pathophysiologic problem in Kartagener's syndrome. CASE PRESENTATION: A 24-year-old man from Gondar town, North-West Ethiopia, presented to University of Gondar Hospital with recurrent episodes of nasal congestion with itching and paranasal discomfort, and productive cough for more than a decade. Clinical and imaging findings revealed chronic sinusitis, bronchiectasis, dextrocardia, and situs inversus. He was treated with orally administered antibiotics, mucolytic, and chest physiotherapy. He was symptomatically better with the above therapy, and started on a long-term low-dose prophylactic antibiotic. CONCLUSIONS: Patients with Kartagener's syndrome exist in Ethiopia as cases of chronic recurrent sinopulmonary infections. As there is no easy, reliable non-invasive diagnostic test for Kartagener's syndrome and the correct diagnosis is often delayed by years, it may cause chronic respiratory problems with reduced quality of life. Genetic counseling and fertility issues should be addressed once Kartagener's syndrome is diagnosed.

Airway Clearance Techniques for Primary Ciliary Dyskinesia; is the Cystic Fibrosis literature portable?

Primary Ciliary Dyskinesia (PCD) is a rare inherited disease with impaired mucociliary clearance. Airway clearance techniques (ACTs) are commonly recommended for patients with PCD to facilitate mucus clearance, despite a lack of evidence in this group. Current physiotherapy practice in PCD is based on evidence extrapolated from the field of Cystic Fibrosis (CF). This paper focuses on the available evidence and outlines challenges in extrapolating evidence between the conditions for best clinical practice.

[Polypous pansinusitis with the deformation of the external nose in a 8 year-old child presenting with the primary ciliary dyskinesia syndrome]. / Polipoznyi pansinusit s deformatsiei naruzhnogo nosa u rebenka 8 let s sindromom pervichnoi tsiliarnoi diskinezii.

This article reports a rare observation of the development of chronic polypous pansinusitis with deformation of the external nose in a 8 year-old child presenting with primary ciliary dyskinesia syndrome. The patient underwent multiple surgical interventions in the preceding period. The key argument in favour of the definitive diagnosis was the results of investigation of ciliated epithelium biopsy taken from the nasal cavity and bronchi in combination with the data obtained by diagnostic endoscopy of the nasal cavity and nasopharynx supplemented by computed tomography. The proposed treatment strategy including endoscopic endonasal pansinusotomy, antibacterial therapy taking into consideration the sensitivity of the seeded microorganism, and hormonal therapy proved optimal for the management of the given patient.

Clinical impact of Pseudomonas aeruginosa colonization in patients with Primary Ciliary Dyskinesia.

BACKGROUND: Airway infections in Primary Ciliary Dyskinesia (PCD) are caused by different microorganisms, including pseudomonas aeruginosa (PA). The aim of this study was to investigate the association of PA colonization and the progression of lung disease in PCD. METHODS: Data from 11PCD centers were retrospectively collected from 2008 to 2013. Patients were considered colonized if PA grew on at least two separate sputum cultures; otherwise, they were classified as non-colonized. These two groups were compared on the lung function computed tomography (CT) Brody score and other clinical parameters. RESULTS: Data were available from 217 patients; 60 (27.6%) of whom were assigned to the colonized group. Patients colonized with PA were older and were diagnosed at a later age. Baseline forced expiratory volume at 1 s (FEV1) was lower in the colonized group (72.4 ± 22.0 vs. 80.1 ± 18.9, % predicted, p = 0.015), but FEV1 declined throughout the study period was similar in both groups. The colonized group had significantly worse CT-Brody scores (36.07 ± 24.38 vs. 25.56 ± 24.2, p = 0.034). A subgroup analysis with more stringent definitions of colonization revealed similar results. CONCLUSIONS: Lung PA colonization in PCD is associated with more severe disease as shown by the FEV1 and CT score. However, the magnitude of decline in pulmonary function was similar in colonized and non-colonized PCD patients.

Primary ciliary dyskinesia ciliated airway cells show increased susceptibility to Haemophilus influenzae biofilm formation.

Non-typeable Haemophilus influenzae (NTHi) is the most common pathogen in primary ciliary dyskinesia (PCD) patients. We hypothesised that abnormal ciliary motility and low airway nitric oxide (NO) levels on airway epithelial cells from PCD patients might be permissive for NTHi colonisation and biofilm development.We used a primary epithelial cell co-culture model to investigate NTHi infection. Primary airway epithelial cells from PCD and non-PCD patients were differentiated to ciliation using an air-liquid interface culture and then co-cultured with NTHi.NTHi adherence was greater on PCD epithelial cells compared to non-PCD cells (p<0.05) and the distribution of NTHi on PCD epithelium showed more aggregated NTHi in biofilms (p<0.001). Apart from defective ciliary motility, PCD cells did not significantly differ from non-PCD epithelial cells in the degree of ciliation and epithelial integrity or in cytokine, LL-37 and NO production. Treatment of PCD epithelia using exogenous NO and antibiotic significantly reduced NTHi viability in biofilms compared with antibiotic treatment alone.Impaired ciliary function was the primary defect in PCD airway epithelium underlying susceptibility to NTHi biofilm development compared with non-PCD epithelium. Although NO responses were similar, use of targeted NO with antibiotics enhanced killing of NTHi in biofilms, suggesting a novel therapeutic approach.

Lung Clearance Index (LCI) is Stable in Most Primary Ciliary Dyskinesia (PCD) Patients Managed in a Specialist Centre: a Pilot Study.

Primary ciliary dyskinesia is a condition in which abnormal cilia structure or function leads to reduced mucociliary clearance and obstructive lung disease. Twenty-nine patients had lung clearance index (LCI) measured in 2009 and we attempted to perform a 5-year follow-up. Only 12 patients could be re-recruited, but in this small group LCI was stable over the 5 years, which confirms previous data showing that spirometry is also stable in these patients over the medium term. The two patients with the highest LCI in 2009 had since died, despite one having relatively preserved spirometry at the time. These data may be used to inform sample size calculations of future studies.