Considerable Comorbidities Research Articles

Impacts of Hospital Acquired Bloodstream Infections in Patients Undergoing Hemodialysis Through a Central Venous Catheter

Background: Hospital acquired infections (HAI) are of interest given their resultant morbidity, mortality, and hospital utilization. Among HAIs, central line associated bloodstream infections result in the highest rates of mortality and additional costs. While all central venous catheters (CVC) carry risk for BSI, long-term catheter use is at increased risk. One population that utilize CVCs for extended durations are those undergoing hemodialysis. While data are available characterizing BSI impacts on outpatient hemodialysis patients, little data exist describing inpatients. The purpose of this study was to characterize the demographics, outcomes, and economics associated with the development of hospital acquired BSI (HA-BSI) in patients undergoing hemodialysis through a CVC (HD-CVC). Methods: All admissions of adult patients in the Premier Healthcare Database with hospital stays including HD-CVC with discharge dates during 2020-2022 were retrospectively evaluated. BSIs were identified by ICD-10 codes and blood culture collection dates. A BSI was deemed hospital acquired if the blood culture date was ≥3 calendar days after admission. Descriptive analyses were undertaken for HA-BSI patients including: baseline demographics, clinical characteristics, and outcomes. Length of stay (LOS), ICU utilization, and estimated costs were evaluated for HAI-BSI and non-BSI populations. Results: 166,394 admissions from 91,448 patients were identified. Of these, 5,722 patients (6.3%) had 5,842 admissions with a HA-BSI. These patients were 58.9% white, 28.3% black, 56.8% male, and 62.9% were aged ≥60years. Patients had considerable comorbidities at baseline with 88.9% having ≥2 Charlson comorbid conditions and 46.9% with ≥6. During the study period, all-cause mortality was 27.8% for HA-BSI patients with 85.5% of deaths occurring while inpatient. Median LOS for patients with HA-BSI was 25 days compared with 6 days for HD-CVC without BSI; patients with HA-BSI were also more likely to require the ICU (65.6% vs. 27.6%). The median ICU LOS was 12 days for HA-BSI versus 34 days for HD-CVC without BSI. Greater intensity of healthcare utilization was reflected in median costs of $402K for HA-BSI, compared with $43K for HD-CVC without BSI. Discussion: We described the characteristics of HD-CVC patients that developed HA-BSI. These patients had many comorbidities and relatively high rates of all-cause in-hospital mortality. Patients were likely to have long LOS, both in-hospital and within the ICU. Collectively, care of these patients was associated with considerable healthcare costs, particularly as compared with HD-CVC patients not developing a HA-BSI. Future studies should characterize risk factors and evaluate potential prevention strategies for this high-risk population.

Effects of COVID-19 Pandemic on Young Individuals - A Mini Review

Background: The COVID-19 pandemic has dominated the last two years of the life of young individuals from every aspect. Medical illness associated with COVID-19 is only one element of the detrimental impact that it has had. The psychological, educational, and social aspects of young individuals have been affected with potentially far-reaching effects. The aim of this review is to determine the negative impact of COVID-19 in each of these areas and inform future practices or policies on the management of young individuals impacted by COVID-19 or future pandemics of this magnitude. Methods: We have collated and analyzed data available on the psychosocial, educational, and social aspects of young individuals in an attempt to understand the negative impact of COVID-19 on this group. Data were collected from an extensive Medline search of relevant articles relating to the effect of COVID-19 on individuals less than eighteen years. Results: Our results show that although young individuals experienced a milder form of COVID-19 in the pandemic, conditions, such as anxiety, depression, and loss of routine, have caused considerable comorbidities in this population. Young individuals have also experienced a greater rise in obesity and a higher incidence of myopia. A key finding of this review showed that children with special needs experienced a lack of continuity of care. Additionally, distant and digital learning presented challenges for children from different backgrounds. Concerns regarding wider issues, such as finance, have also directly impacted young individuals. Vaccination for COVID-19 among children has also raised important ethical issues. Conclusion: COVID-19 has negatively impacted the psychological, physical, and emotional needs of young individuals with potentially far-reaching consequences. A combined psychosocial and clinical approach to tackling the specific needs of young individuals is essential to support the needs and management of individuals affected by the pandemic. The findings of our review recommend measures to include balancing screen time with outdoor activity and encouraging the continued education of children regarding good health practices and vaccination in particular. We hope that this will inform future practices or policies on the management of young individuals impacted by COVID-19 or future pandemics of this magnitude.

Risk of Chronic Kidney Disease in Pneumoconiosis: Results from a Retrospective Cohort Study (2008-2019).

Pneumoconiosis has considerable comorbidities, most notably pulmonary and cardiovascular diseases. However, the relationship between pneumoconiosis and chronic kidney disease (CKD) is largely unknown. The present study aimed to use a retrospective cohort study design to further clarify the association between pneumoconiosis and subsequent CKD risk. This is a nationwide, population-based, retrospective cohort study that used data from Taiwan's National Health Insurance Database. Between 2008 and 2018, 17,952 newly diagnosed patients were included in the pneumoconiosis cohort, while 71,808 individuals without pneumoconiosis were included in the comparison cohort, with a propensity score matching for age, gender, and date of pneumoconiosis diagnosis. The development of CKD was monitored until the end of 2019. The risk was assessed using Cox proportional hazard regression models. After controlling for age, gender, and comorbidity, the overall incidence of CKD was 1.69-fold higher in the pneumoconiosis cohort than in the comparison cohort (19.71 vs. 11.76 per 1000 person-years, respectively, p < 0.001), with an adjusted hazard ratio of 1.83 (95% confidence interval: 1.73-1.93). Stratified analyses by age group, gender, and presence of comorbidity revealed that the adjusted hazard ratios of CKD associated with pneumoconiosis remained significant (8/9). Furthermore, pneumoconiosis and tri-high (hypertension, hyperglycemia, and hyperlipidemia) interact positively with CKD development (p < 0.001). Patients with pneumoconiosis had a significantly higher risk of developing CKD than those without. Pneumoconiosis combined with hypertension, hyperglycemia, or hyperlipidemia would increase the risk even further. More studies are required to understand the possible pathophysiological mechanisms.

Irritable Bowel syndrome and Psychiatric Comorbidities: A narrative review

Irritable bowel syndrome (IBS) is the most commonly diagnosed illness by gastroenterologists. These symptoms occur widely in the general population at all ages and in both sexes. The condition is a considerable health-care burden, accounting for approximately half of all referrals to gastrointestinal clinics. The prevalence of IBS varies according on geographic region, demographic, and diagnostic criteria employed. IBS pathogenesis is complicated and poorly understood. Gut microbiota, small intestinal bacterial overgrowth (SIBO), visceral hypersensitivity, disruption of the gut-brain axis, psychosocial distress, and altered GI motility all are proposed as potential risk factors. Inflammatory bowel syndrome (IBS) is associated with considerable psychosocial comorbidities, which have an impact on patient quality of life, disease progression, and health-care expenditures. The present article reviews the latest evidence on the aetiology IBS, with a focus on psychiatric comorbidities and available management available.

A new approach in bariatric operations: bridged mini gastric by-pass. Is rabbit model suitable for an experimental study?

Obesity is a global health epidemic with considerable co-morbidities. The increasing demand for bariatric surgery has led to the emergence of new techniques. We modified previously described Mini Gastric By-pass(MGB) technique via leaving a bridge at the most cranial 2 cm of the fundus of the human stomach to the follow-up and treatment of the remnant stomach and duodenum. We would like to entitle this new technique as Bridged MGB and aimed to apply on rabbits as an experimental study. The study was performed in the experimental animal laboratory of university after ethical approval was taken from the local ethics committee. Described new technique was applied to 2.1 and 3.2 kg 2 New Zealand rabbits. As a result of the operations, one of the rabbits died on the day of the operation; the other rabbit was exitus postoperatively on the third day. In autopsies, although no problem was detected at the anastomoses, necrosis was detected in the large curvature of both rabbits. Rabbit, one of the popular experimental animals, has been shown to be different from the human gastrointestinal system in both arterial and topographic aspects and it has been emphasized that it varies according to the species and even the diet and the climate. We believe that our study failed as a result of these differences and that animals more similar to humans should be used in gastrointestinal experimental studies.

Pediatric Psoriasis: From New Insights into Pathogenesis to Updates on Treatment.

Psoriasis is a chronic inflammatory systemic disease primarily affecting the skin, but which often involves considerable comorbidities as well. One-third of psoriasis cases start during childhood. In pediatric psoriasis, an association with several medical comorbidities is also indicated. Furthermore, because of its chronic nature and frequent relapses, psoriatic patients tend to require long-term treatment and experience negative impacts on their quality of life. Considering the different clinical characteristics of pediatric psoriasis, it has recently been presented that the pathogenesis of pediatric psoriasis is distinct from adult psoriasis. Treatment for pediatric psoriasis usually involves the same methods as for adults. However, most treatments in pediatric psoriasis are used off-label and research in this regard is still lacking. Targeted therapies involving newly developed biologics are also increasingly being applied to psoriasis in children. This review summarizes the clinical characteristics of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and treatments in pediatric psoriasis. This was undertaken to widen the understanding of these relevant aspects and to provide better management of pediatric psoriasis by clinicians.

AB005. OP-5 A new approach in bariatric operations: bridged mini gastric bypass is rabbit model suitable for an experimental study?

Background: Obesity is a global health epidemic with considerable co-morbidities. The increasing demand for bariatric surgery has led to the emergence of new techniques. We modified previously described mini gastric bypass (MGB) technique via leaving a bridge at the most cranial 2 cm of the fundus of human stomach to the follow-up and treatment of the remnant stomach and duodenum. We would like to entitle this new technique as Bridged MGB (Sumer’s technique) and aimed to apply on rabbits as an experimental study.

New Perspectives on Difficult Asthma; Sex and Age of Asthma-Onset Based Phenotypes

Asthma is a diverse condition that differs with age and sex. However, it remains unclear how sex, age of asthma onset, and/or their interaction influence clinical expression of more problematic adult "difficult" asthma. To better understand the clinical features of difficult asthma within a real-world clinical setting using novel phenotypic classification, stratifying subjects by sex and age of asthma onset. Participants in a longitudinal difficult asthma clinical cohort study (Wessex AsThma CoHort of difficult asthma; WATCH), United Kingdom (n= 501), were stratified into 4 difficult asthma phenotypes based on sex and age of asthma onset (early <18 years or adult ≥18 years) and characterized in relation to clinical and pathophysiological features. The cohort had more female participants (65%) but had similar proportions of participants with early- or adult-onset disease. Early-onset female disease was commonest (35%), highly atopic, with good spirometry and strong associations with some physical comorbidities but highest psychophysiologic comorbidities. Adult-onset females also had considerable psychophysiologic comorbidities and highest obesity, and were least atopic. Amongst male subjects, proportionately more had adult-onset disease. Early-onset male disease was rarest (14%) but associated with worst lung function, high smoking, atopy, and fungal sensitization. Despite shortest disease duration, adult-onset males had highest use of maintenance oral corticosteroid, poor lung function, and highest fractional exhaled nitrogen oxide in spite of highest smoking prevalence. This study shows that sex, age of asthma onset, and their interactions influence different clinical manifestations of difficult asthma and identifies a greater risk for lung function loss and oral corticosteroid dependence associated with smoking in adult-onset male subjects.

Incidence, outcome, and risk factors for recurrence of nosocomial Clostridioides difficile infection in adults: A prospective cohort study

BackgroundNosocomial Clostridioides difficile infection (CDI) complicates up to 1% of all hospital admissions and is associated with considerable health burden. AimsTo determine the incidence and outcomes of nosocomial CDI at a major University Medical Center. MethodsConsecutive adult nosocomial CDI cases were prospectively identified. Stool samples were collected for ribotyping and antibiotic resistance testing. Patients were followed for eight weeks after discharge for relapse. ResultsOver a 2-year period, 215 patients developed nosocomial CDI (incidence 2:1000) and 200 (mean age 62.2±19.6 years) gave informed consent. Mean hospital stay was 23.3±28.9 days (range 0–278). Infection was diagnosed within 7 days of admission (range 0–95) in 129 patients (64.5%). More than two-thirds (69.0%) were previously hospitalized within 12 weeks of the index hospitalization. Twenty five percent received prior antibiotics within eight weeks. Fifty-two patients (26.0%) did not receive antibiotics prior to diagnosis. Considerable comorbidities (Charlson Comorbidity Index ≥8) were noted in 33.5% of patients. Recurrence occurred in 43 patients (21.5%). On multivariate logistic regression, fluoroquinolone exposure was the only predictor of recurrence (OR=2.9, 95%CI 1.1–7.7). Overall mortality was 14.0% and CCI ≥8 was the only predictor on multivariate analysis (p=0.004). Genotyping did not identify any known hypervirulent strains and all isolates were susceptible to metronidazole and vancomycin. ConclusionAntibiotic exposure, comorbidities, and prior hospitalization constitute the major risk factors for nosocomial CDI. Recurrence is common and is associated with fluoroquinolones exposure. High baseline comorbidity score was the only predictor of increased mortality in this prospective cohort.

Venetoclax and Cytarabine in AML Transformed from Myelofibrosis

Background Acute myeloid leukemia (AML) accounts for 1% of all newly diagnosed cancers with a mean age at diagnosis of 68. Although the majority present de novo, AML can be secondary to conditions such as myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF). The subset of patients with AML transformed from MPN continues to remain a therapeutic challenge with little data to support clinical efficacy. A large retrospective review of 273 patients revealed no significant improvement in overall survival in this patient population for those diagnosed between 1989 and 2016. Prognosis remains dismal with an overall survival of 5-7 months. Treatment options are limited and often with little proven clinical utility. Even the addition of hypomethylating agents to treatment options has failed to show any improvement in survival necessitating the investigation of new treatment options (Chihara et al, ASH 2016). In this case series, we present two AML cases that have transformed from myelofibrosis and were successfully treated with the combination of cytarabine and venetoclax. Objective Our primary objective was to determine the clinical efficacy of the combination of cytarabine and venetoclax in patients with myelofibrosis with leukemic transformation. Methods This is an observational, retrospective case series of two patients that were treated with cytarabine and venetoclax at Virginia Commonwealth University from 2018 to 2019. Both patients had previously been confirmed as meeting WHO criteria for myelofibrosis on bone marrow examination. Upon transformation to acute myeloid leukemia, again confirmed on bone marrow biopsy, both patients were transitioned to the following regimen: cytarabine 20 mg/m2 on days 1-10 of 28-day cycle in combination with venetoclax with rapid dose escalation to goal of 600mg daily with dose adjustments for medication interactions. The patient's response to therapy and side effect monitoring were performed at regular intervals in the outpatient clinic. Results Our study consisted of two females, age 65 (patient 1) and 71 (patient 2) with a median age of 68 and bone marrow biopsy confirmed diagnosis of myelofibrosis. Both females had grade 3+ fibrosis on marrow examination and both harbored JAK2 mutations on initial diagnosis of myelofibrosis. Patient 2 also demonstrated a 20q deletion. Neither female was deemed a suitable candidate for transplantation due to their age and considerable comorbidities. On transformation to leukemia, blast count burden was 27% and 23%, respectively. Patient 1 had received decitabine prior to the cytarabine/venetoclax regiment while the other had no previous therapy for her myelofibrosis or leukemia. Patient 1 was maintained on the regiment with for 10 months and nearly completed 9 cycles before patient decompensated and was transitioned to comfort care and eventually died. Complications during her treatment course included an elevated uric acid requiring a dose of rasburicase, neutropenic fever and subdural hematoma that resolved without any intervention. Patient 2 has completed 6 cycles of therapy and is now 8 months post initiation of therapy. Her most recent bone marrow biopsy showed a hypocellular bone marrow (20-30% cellularity) and severe myelofibrosis (reticulin 3/3+) with less than 1% blasts. She remains independent of transfusions. Conclusions Our case series demonstrates that the combination of cytarabine and venetoclax can be effectively used in patients with AML transformed from myelofibrosis. In a disease historically with an overall survival of 6 months, one patient survived 10 months and the other is 8 months out and currently in remission from her AML on her most recent bone marrow biopsy, and independent of transfusions. Overall, therapy has been well tolerated with manageable adverse events. Although future prospective studies are needed, the combination of cytarabine and venetoclax offers a reasonable treatment option for secondary AML transformed from myelofibrosis. Disclosures Yazbeck: Gilead Sciences: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Rituximab and Bendamustine for First-Line Treatment of Frail or Elderly Patients with Aggressive B-Cell Lymphoma: Final Results of the Prospective Phase-II Brenda Trial of GLA (German Lymphoma Alliance)

Rituximab and Bendamustine for First-Line Treatment of Frail or Elderly Patients with Aggressive B-Cell Lymphoma: Final Results of the Prospective Phase-II Brenda Trial of GLA (German Lymphoma Alliance)

Patients with Moderate to Severe Psoriasis Associate with Higher Risk of Depression and Anxiety Symptoms: Results of a Multivariate Study of 300 Spanish Individuals with Psoriasis.

Psoriasis is a chronic skin disease associated with considerable physical and psychological comorbidities. Stress and emotional disturbances have been implicated in both triggering the onset and exacerbation of psoriasis. In order to determine the level of perceived stress and mood alterations in patients with psoriasis and their association with disease severity, 300 individuals completed diverse validated questionnaires assessing stress and psychological mood. Evaluation of perception of disease was also measured. A significant association between psoriasis severity and mood, emotional disturbances and an impact on assessments of the quality of life were observed. Particularly, Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale and Hospital Anxiety and Depression Scale for Depression detected a significant risk for depression in relation to the disease severity. The association between depression features, anxiety and perceived stress with psoriasis severity is important and can influence the appropriate management of psoriasis.

Female sex is not a risk factor for post procedural mortality in coronary bypass surgery in the elderly: A secondary analysis of the GOPCABE trial.

ObjectiveFemale sex is considered a significant risk in cardiac surgery and is included in the majority of scores for risk assessment. However, the evidence is controversial and older women undergoing cardiac surgery have not specifically been investigated. We assessed the influence of female sex on surgical risk (30-day mortality) in a secondary analysis of the GOPCABE trial (German Off-Pump Coronary Artery Bypass grafting in the Elderly (GOPCABE) trial, comparing on- to off-pump) and also evaluated its impact on risk prediction from commonly used risk scores.MethodsWe performed logistic regression analyses on the GOPCABE trial population, where patients were randomized to either on- or off-pump CABG. The study was performed in 12 cardiac surgery centers in Germany and analyzed 2394 patients having undergone CABG at age ≥75 years (1187 on-pump, 1207 off-pump). Of the 2394 patients, 755 (32%) were women. The logistic EuroSCORE and the German KCH score were calculated as expected (E) mortality and values were compared to observed (O) 30-day mortality (O/E ratio).ResultsThere was no difference in mortality or major cardiovascular adverse events after 30 days between men and women for both on- and off-pump CABG (men: on- vs. off-pump OR = 0.90, 95%-CI: [0.63;1.27]; women: on- vs. off-pump OR = 1.07, 95%-CI: [0.62;1.87]). Therefore, groups were combined for further analyses. Both men and women had considerable and similar comorbidities. Expected mortality was significantly higher for women than for men (logistic EuroSCORE: 8.88±6.71% vs. 7.99±6.69%, p = 0.003; KCH score: 4.42±3.97% vs. 3.57±3.65%, p = 0.001). However, observed mortality rates (O) tended to be even lower in women (2.1% vs. 3.0%). The O/E ratio was closer to 1 in men than in women (0.84 vs. 0.47). Excluding female sex from the risk models increased O/E ratio to 0.69.ConclusionsFemale sex is not a risk factor in coronary bypass surgery in the GOPCABE population. The result is the same for on- and off-pump surgery. Since female sex is a component of most risk scores, the findings may identify a potential inaccuracy in current surgical risk assessment, specifically for elderly women.Trial registrationClinicaltrials.gov GOPCABE trial No. NCT00719667

Course of Tourette syndrome and comorbidities in a large prospective clinical study

Objective Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by tics and frequent comorbidities. Although tics often improve during adolescence, recent studies suggest that comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) tend to persist. This large prospective follow-up study describes the clinical course of tics and comorbidities during adolescence and the prevalence of coexisting psychopathologies. Method The clinical cohort was recruited at the Danish National Tourette Clinic, and data were collected at baseline (n = 314, age range 5–19 years) and at follow-up 6 years later (n = 227) to establish the persistence and severity of tics and comorbidities. During follow-up, the Development and Well-Being Assessment (DAWBA) was used to diagnose coexisting psychopathologies. Repeated measures of severity scores were modeled using mixed effects models. Results Tic severity declined yearly (0.8 points, CI: 0.58–1.01, on the Yale Global Tic Severity Scale [YGTSS]) during adolescence; 17.7% of participants above age 16 years had no tics, whereas 59.5% had minimal or mild tics, and 22.8% had moderate or severe tics. Similarly, significant yearly declines in severity of both OCD (0.24, CI: 0.09–0.39, on the Yale–Brown Obsessive Compulsive Scale for Adults [Y-BOCS] and Yale–Brown Obsessive Compulsive Scale for Children [CY-BOCS]) and ADHD (0.42, CI: 0.32–0.52, DSM-IV ) were recorded. At follow-up, 63.0% of participants had comorbidities or coexistent psychopathologies, whereas 37.0% had pure TS. Conclusion Severity of tics, OCD, and ADHD were significantly associated with age and declined during adolescence. However, considerable comorbidities and coexisting psychopathologies persist throughout adolescence and require monitoring by clinicians.

Pediatric Psoriasis.

Psoriasis is a chronic inflammatory systemic disease associated with an important physical and physiological burden. It primarily affects the skin, but it is associated with several serious medical co-morbidities. One third of total psoriatic cases have their onset during the pediatric age, although some of them may not be diagnosed until the patient reaches adulthood. Additionally, in the pediatric age, there is an association with several medical co-morbidities; thus, an early recognition of the disease and a subsequent appropriate approach may delay or even prevent considerable co-morbidities. Because children are not just 'small adults', specific guidelines for the diagnosis, management, and treatment of psoriasis are of extreme importance. However, these guidelines are still lacking in this age group. Most of the psoriasis treatments used in adults are not officially approved for the pediatric age and require off-label prescription. Moreover, efficacy and safety studies are lacking in this population, especially with long-term follow-up and outcomes. Many biologic agents have been recently approved for the treatment of psoriasis in children, while others are currently being studied. This bibliographic review aims to summarize the most relevant aspects, as well as updated information about the epidemiology, pathogenesis, clinical features, diagnosis, co-morbidities and treatment of pediatric psoriasis.

Course of Tourette Syndrome and Comorbidities in a Large Prospective Clinical Study

Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by tics and frequent comorbidities. Although tics often improve during adolescence, recent studies suggest that comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) tend to persist. This large prospective follow-up study describes the clinical course of tics and comorbidities during adolescence and the prevalence of coexisting psychopathologies. The clinical cohort was recruited at the Danish National Tourette Clinic, and data were collected at baseline (n= 314, age range 5-19 years) and at follow-up 6years later (n= 227) to establish the persistence and severity of tics and comorbidities. During follow-up, the Development and Well-Being Assessment (DAWBA) was used to diagnose coexisting psychopathologies. Repeated measures of severity scores were modeled using mixed effects models. Tic severity declined yearly (0.8 points, CI: 0.58-1.01, on the Yale Global Tic Severity Scale [YGTSS]) during adolescence; 17.7% of participants above age 16 years had no tics, whereas 59.5% had minimal or mild tics, and 22.8% had moderate or severe tics. Similarly, significant yearly declines in severity of both OCD (0.24, CI: 0.09-0.39, on the Yale-Brown Obsessive Compulsive Scale for Adults [Y-BOCS] and Yale-Brown Obsessive Compulsive Scale for Children [CY-BOCS]) and ADHD (0.42, CI: 0.32-0.52, DSM-IV) were recorded. At follow-up, 63.0% of participants had comorbidities or coexistent psychopathologies, whereas 37.0% had pure TS. Severity of tics, OCD, and ADHD were significantly associated with age and declined during adolescence. However, considerable comorbidities and coexisting psychopathologies persist throughout adolescence and require monitoring by clinicians.

Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Deficiency

Background:Mutations in the zinc finger transcription factor GATA2 are responsible for: MonoMAC, monocytopenia with atypical mycobacterial infection (MAC); DCML, dendritic cell, monocyte and lymphoid cell deficiency; Emberger syndrome with lymphedema and monosomy 7; and familial myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). Allogeneic hematopoietic stem cell transplant (HSCT) represents the only definitive therapy for GATA2 deficiency.Methods: We carried out myeloablative allogeneic hematopoietic stem cell transplant (HSCT) on 24 patients (mean age 24.9 years; range 16 to 46 years) with mutations in GATA2, or the MonoMAC syndrome, during the preceding three years. Three matched related donor (MRD) recipients and 13 matched unrelated donor (URD) recipients received busulfan 3.2 mg/kg/day and fludarabine 40 mg/m2/day on day's -6, -5, -4, and -3. Eight haploidentical related donor recipients received cyclophosphamide 14.5 mg/kg on day's -6 and -5, fludarabine 30 mg/m2/day on day's -6 to -2, busulfan 3.2 mg/kg/day on day's -4 and -3, and 200 cGy TBI on day -1. The majority of the MRD and URD recipients (n=13) received tacrolimus and short course methotrexate post-transplant as graft-versus host disease (GVHD) prophylaxis; three URD, while three received post-transplant cyclophosphamide (PT/CY) on days + 3 and +4 followed by tacrolimus and mycophenolate mofetil as post-transplant immunosuppression for GVHD. All 8 haploidentical related donor recipients received PT/CY as described followed by tacrolimus/methotrexate.Results:Twenty-two of the 24 patients are alive and disease-free at a mean follow-up of 13 months (range, 2 to 36 months). One matched URD recipient died from persistent AML 110 days post-transplant, and one matched URD recipient died from GVHD 2 years post-transplant. Despite a previous history of MAC in 11 patients, including 3 patients with active MAC at the time of HSCT, there were no recurrences of MAC during or following HSCT. Similarly, 13 patients had MDS with cytogenetic abnormalities at the time of HSCT (trisomy 8, monosomy 7, 5q-, trisomy 1q), and all 13 had resolution of their cytogenetic abnormalities with no late relapses following HSCT. Three patients had lymphedema at the time of HSCT (Emberger syndrome), which was not reversed. Twenty-three of the 24 patients had complete reconstitution of the monocyte, NK, and B-lymphocyte compartments, which were severely deficient pre-transplant. One URD who received PT/CT had poor graft reconstitution and required a CD34+ donor cell boost three months post-transplant. Four of the 13 MRD and URD recipients who received tacrolimus/methotrexate developed grade III-IV acute GVHD, and 3 of the 7 who were more than one-year post-HSCT developed moderate to severe chronic GVHD. No haploidentical related donor recipient developed grade III-IV GVHD or moderate to severe chronic GVHD.Conclusions: Myeloablative HSCT in GATA2 deficiency results in uniform engraftment and reversal of the hematologic, cytogenetic, and clinical manifestations of clinical manifestations of GATA2 deficiency with low regimen-related toxicity, even in this cohort of patients with considerable co-morbidities. We are currently using PT/CY in MRD and URD recipients with normal, favorable, or intermediate cytogenetics with isolated trisomy 8 to reduce the incidence of acute and chronic GVHD. We anticipate that with HSCT earlier in the clinical course, before significant organ damage or clonal evolution of MDS to AML occurs, the outcome of allogeneic HSCT in patients with GATA2 deficiency will continue to improve. Haploidentical related donor transplant appears to be particularly well suited for this disease, especially when the disease presents as a hypocellular MDS with or without trisomy 8. DisclosuresNo relevant conflicts of interest to declare.

Cowper's syringocele: A rare differential diagnosis of infravesical obstruction in boys and young adults

Cowper's syringocele is a cystic dilation of the bulbourethral gland duct, initially defined by Maizels etal. in 1983. Although obstructive and non-obstructive types of this rare anomaly are described, clinical symptoms are highly unspecific. Therefore, we report 12 cases of children and young adults diagnosed with Cowper's syringocele to further clarify clinical course, comorbidity and treatment strategies. We retrospectively collected clinical data of 12 children and young adults from birth to 18.5 years (median 7.2 years) who had been treated in four different institutes during a period of 16 years. The primary specific diagnostic work-up consisted of ultrasound, cystourethrography, and cystoscopy. 3Older patients with a median age of 11.8 years clinically presented with obstructive voiding pattern or gross hematuria; infants with a median age of 0.6 years presented with febrile urinary tract infections (UTIs). After cystoscopic confirmation in all patients, endoscopic treatment was possible in nine; open surgical resection was necessary in three patients. Because of intrauterine megacystis and chronic renal failure, one boy underwent suprapubic diversion with a cystostomy soon after birth. Owing to urological comorbidity or later complications, additional procedures were necessary, for example, resection of minor urethral valves, prophylactic circumcision for UTI, endoscopic or open antireflux procedures, and occasionally complex bladder reconstructions in the long term. According to our data, the initial clinical symptoms of Cowper's syringocele were related to presenting age rather than the previously described type of syringocele according to Maizels etal. Infants presented with febrile UTIs; however, older boys and young adults had mainly voiding problems or nocturnal enuresis. Therefore, the clinical significance of the described syringocele types must be questioned. Eighty-three percent of our patients showed additional urological pathology such as vesicoureterorenal reflux, ureteropelvic junction obstruction, megaureter, or minor urethral valves. Thus, Cowper's syringocele hardly seems to be an isolated pathology. Although rare, Cowper's syringoceles should be considered in differential diagnosis of infravesical obstruction in boys and young adults. Diagnostics are usually justified by presenting symptoms such as UTI or urinary flow impairment, which seem to be age dependent. Despite modern diagnostic tools, diagnosis is usually made by cystourethrography and sometimes accidentally by cystoscopy. Considerable urological comorbidities and consecutive bladder dysfunction need long-term follow-up.

Severe community-acquired pneumonia

Severe community-acquired pneumonia (CAP) remains a frequent reason for admission to hospital. It is the most common cause of septic shock requiring escalation to treatment within an intensive care unit (ICU). Despite earlier recognition and recent advances in supportive care, severe CAP is still associated with substantial morbidity and mortality, more often seen in the elderly and those with considerable comorbidities.

Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Deficiency

▪Background: Mutations in the zinc finger transcription factor GATA2 are responsible for: MonoMAC, monocytopenia with nontuberculous mycobacterial (NTM) infections; DCML, dendritic cell, monocyte and lymphoid cell deficiency; Emberger's syndrome with lymphedema and monosomy 7; and familial myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). Allogeneic hematopoietic stem cell transplant (HSCT) represents the only definitive therapy for GATA2 deficiency.Methods: Eleven patients with GATA2 deficiency received a myeloablative-conditioning regimen (2 matched related donors or MRD, 4 matched unrelated donors or URD, and 5 haploidentical related donors. MRD and URD received busulfan 3.2 mg/kg/day and fludarabine 40 mg/m2/day on days -6, -5, -4, and -3. Haploidentical related donors received cyclophosphamide 14.5 mg/kg on day's -6 and -5, fludarabine 30 mg/m2/day on day's -6 to -2, busulfan 3.2 mg/kg/day on day's -4 and -3, and 200 cGy TBI on day -1. MRD and URD recipients received tacrolimus and short course methotrexate post-transplant, while haploidentical related donor recipients received cyclophosphamide 50 mg/kg/day on days + 3 and +4 followed by tacrolimus and mycophenolate mofetil as post-transplant immunosuppression for graft-versus-host disease.Results: Ten of the 11 (91%) of patients are alive and disease-free at a mean follow-up of 12 months (range 1 mo to 24 mo). One URD recipient died from persistent acute myelogenous leukemia. Four patients developed graft-versus-host disease, one case Grade 4. All 10 patients who survived had complete reconstitution of the monocyte, NK, and B-lymphocyte compartments, the three cell compartments that were severely deficient pre-transplant. All 10 patients had reversal of the infection susceptibility phenotype. In particular, there were no recurrences of NTM infections. Importantly, all 10 patients had correction of the cytogenetic abnormalities present pre-transplant (5 patients with trisomy 8 and 1 patient with monosomy 7).Conclusions: Myeloablative HSCT in GATA2 deficiency results in uniform engraftment and reversal of the hematologic, cytogenetic, and clinical manifestations of GATA2 deficiency. There was a low regimen-related toxicity, even in this cohort of patients with considerable co-morbidities. We anticipate that with HSCT earlier in the clinical course, before significant organ damage or clonal evolution of MDS to AML or CMML occurs, the outcome of allogeneic HSCT in patients with GATA2 deficiency will continue to improve. Haploidentical related donor transplant appears to be particularly well suited for this disease, especially when the disease presents as a hypocellular myelodysplastic syndrome. DisclosuresNo relevant conflicts of interest to declare.