Multisystem inflammatory syndrome in children associated with COVID-19 presenting as cervical inflammation.

AIM: The major clinical manifestations multisystem inflammatory syndrome in children (MIS-C) are fever, gastrointestinal and cardiac. The aim of this study was to describe MIS-C in a series of patients who presented primarily with cervical manifestations. METHODS: We retrospectively reviewed medical records of all patients who met the Centers for Disease Control and Prevention and World Health Organization MIS-C diagnostic criteria treated at Hadassah-Hebrew University Medical Center between April 2020 and September 2021. RESULTS: Of 37 children diagnosed with MIS-C (median age: 10.2 years, range 1.5-18 years, 20 male) five, 13.5% (median age: 14.4 years, range 9.2-17.5 years) presented with cervical symptoms mimicking neck infections. One was hospitalised with a working diagnosis of retropharyngeal abscess, and four with acute cervical lymphadenitis that did not respond to early antibiotic treatment. All developed full MIS-C phenotype. CONCLUSION: MIS-C may present as cervical inflammation. An ill-appearing child with symptoms and/or signs of cervical inflammation should be evaluated for clinical and laboratory features of MIS-C, thereby facilitating prompt treatment of this potentially fatal disorder.

Pathogenic Variants in NUP214 Cause "Plugged" Nuclear Pore Channels and Acute Febrile Encephalopathy.

We report biallelic missense and frameshift pathogenic variants in the gene encoding human nucleoporin NUP214 causing acute febrile encephalopathy. Clinical symptoms include neurodevelopmental regression, seizures, myoclonic jerks, progressive microcephaly, and cerebellar atrophy. NUP214 and NUP88 protein levels were reduced in primary skin fibroblasts derived from affected individuals, while the total number and density of nuclear pore complexes remained normal. Nuclear transport assays exhibited defects in the classical protein import and mRNA export pathways in affected cells. Direct surface imaging of fibroblast nuclei by scanning electron microscopy revealed a large increase in the presence of central particles (known as "plugs") in the nuclear pore channels of affected cells. This observation suggests that large transport cargoes may be delayed in passage through the nuclear pore channel, affecting its selective barrier function. Exposure of fibroblasts from affected individuals to heat shock resulted in a marked delay in their stress response, followed by a surge in apoptotic cell death. This suggests a mechanistic link between decreased cell survival in cell culture and severe fever-induced brain damage in affected individuals. Our study provides evidence by direct imaging at the single nuclear pore level of functional changes linked to a human disease.

Ultrasonographic features can predict outcome of conservative management of acute appendicitis in children.

PURPOSE: To determine whether specific ultrasonographic features can predict failure of conservative treatment of acute appendicitis. METHODS: A 2-year retrospective study was conducted on children admitted with acute appendicitis. Those with uncomplicated appendicitis diagnosed solely by ultrasound, and treated conservatively, were followed 18-24 m to assess treatment outcome. Management was considered successful if recurrent acute appendicitis was not observed during follow-up. Appendix diameter, wall thickness, presence of mucosal ulceration, hyperechogenic fat, free fluid, and lymph nodes were evaluated as potential discriminatory ultrasonographic predictors. T-tests, chi-square, sensitivity, specificity, and odds ratios were calculated. RESULTS: Out of 556 consecutive patients that were admitted with acute appendicitis, 180 (32%) managed conservatively. One hundred eleven (62%) imaged by US only. Ninety-two out of 111 (83%) were followed 18-24 m to assess treatment outcome, and 19/111 (17%) were lost to follow-up. Conservative management was successful in 72/92 (78.2%), with treatment failure in 20/92 (21.8%) (5/92 (5.4%) with recurrent acute appendicitis and 15/92 (16.3%) underwent appendectomy). Of the ultrasonographic features studied, mucosal ulceration demonstrated statistically significant predictive value. Fifteen out of 20 (75%) treatment failures had mucosal ulceration, compared to 21/72 (29.2%) of the patients with successful treatment (p < 0.001). This yielded a positive odds ratio of 7.3 (2.3-22.6, 95% CI), 70.8% (58.9-80.9, 95% CI) specificity, and 75% (50.9-91.3, 95% CI) sensitivity. Positive predictive value was 41.6% (31.5-52.5, 95% CI) while intact mucosa had negative predictive value of 91% (82.4-95.6, 95% CI) for conservative management success. CONCLUSION: The presence or absence of appendiceal mucosal ulceration at ultrasound can predict conservative management outcome in the setting of acute appendicitis, potentially improving pediatric patient selection for conservative management.

Parenchymal echotexture changes as a predictor of viability in testicular torsion.

INTRODUCTION: Preoperative test that can predict the salvageability of the torsed testis may add essential information to the surgeon managing testicular torsion (TT), this can assist with patients' and parents' expectations, particularly with nonviable testes. We aimed to examine if parenchymal echotexture changes in preoperative ultrasound can predict irreversible hemorrhagic necrosis. MATERIALS AND METHODS: Preoperative ultrasound studies of 154 patients with TT were reviewed by 3 raters (2 radiologists and 1 urologist). The raters were asked to categorize the affected testicular parenchymal echotexture into one of the following categories: (1) normal (identical to the contra-lateral testis), (2) homogenous hypoechoic, or (3) focal heterogeneous echotexture. Testis non-viability was defined macroscopically during surgical exploration and correlated with the US results. Sensitivity, specificity, and positive and negative predicting values of the proposed diagnostic test were calculated. Cohen's kappa coefficient was used to determine inter-rater agreement. RESULTS: A total of 54/154 patients had a nonviable testis. Mean of 59.5% cases was classified as category 1, 27.3% cases as category 2, and 13.2% cases as category 3. Testicular necrosis was 12%, 34%, and 92% in each category, respectively. Category 3 classified non-viability with a mean specificity of 99.3% and with a high inter-rater agreement level (Cohen's kappa coefficient of 0.830). Mean positive predictive value of 97% and mean negative predictive value of 74.3%. The mean sensitivity of this test however was low 39.7%. CONCLUSION: Ultrasound finding of focal parenchymal echotexture heterogeneous changes is highly specific although not sensitive, for nonviable testis. The presence of this finding reassures non-viability in over 99%.

Pyogenic sacroiliitis in children: don't forget the very young.

Pyogenic sacroiliitis (PS) is rare with less than 100 pediatric cases reported in the medical literature. To better characterize PS in the pediatric population, we investigated a series of children presenting with PS. Retrospective data analysis was done at an academic tertiary center between the years of 2000 and 2017. All hospitalized children ≤ 16 years of age with PS were evaluated. Of the 894 children hospitalized with osteoarticular infections, 18 were diagnosed with PS (2%) and are included in the review. Two clinically distinct groups were identified. PS in infants (n = 13, 72.2%, mean age 1.1 years) had an indolent course and a faster recovery without any bacterial source identified. In contrast, the group of older children (n = 5, 27.8%, mean age 11.6 years) had a more complicated course and a higher rate of identified bacterial infections.Conclusion: We describe an under-recognized entity of PS in infants with a mild clinical course and fast recovery that differ from the "classical" septic sacroiliitis. Infants with PS did not suffer from invasive complications, and pathogen characteristics of older children were not identified. Infants with fever, irritability, decreased range of motion in the pelvic area, and pain during diapering should alert the clinician to this diagnosis. What is Known: • Pediatric pyogenic sacroiliitis is an extremely rare condition usually caused by Staphylococcus aureus with highest incidence in adolescents. • The diagnosis of PS is challenging due to its rarity and difficulty in assessing the sacroiliac joint. What is New: • We describe an under-recognized entity of PS in infants with a mild clinical course, without invasive complications and with fast recovery that differ from "classical" septic sacroiliitis. • Infants with fever, irritability, decreased range of motion in the pelvic area and pain during diapering should raise clinical suspicion of this diagnosis.

Early recurrence of ileocolic intussusception after successful air enema reduction: incidence and predisposing factors.

PURPOSES: Early recurrent ileocolic intussusception (RICI) is a rare event. We aimed to estimate the rate of RICI and identify predisposing factors for early recurrence for children treated in a tertiary-care academic medical center. METHODS: Consecutive children who were diagnosed with ileocolic intussusception (ICI) during the years 2005-2015 and had successful enema reduction were included. Demographic, clinical, imaging, and laboratory data were recorded for analysis. Ultrasound and fluoroscopy images were reviewed. Early RICI was defined as recurrence within 48 h. RESULTS: Two hundred forty-five episodes of intussusception in 210 patients, ages 2 to 77 months (mean 12.7), were included. Six patients (2.45%) had a RICI between 7 and 28 h (mean 17 h) after initial successful reduction. A total of 5/6 recurrences (83.3%) were in winter months. In the group without early recurrence, only 19.6% of the cases presented during the winter (p = 0.001). Mean age in the early recurrence group was 23 months compared to 12.4 months children with no early recurrence (p = 0.016). All other analyzed parameters were comparable for the groups. CONCLUSION: Early RICI is a relatively rare event that may not justify routine admission and long observation. The approach should be individual, based on the clinical picture.

Use of Unenhanced Abdominal Computed Tomography for Assessment of Acute Non-Traumatic Abdominal Pain in the Emergency Department.

BACKGROUND: Acute non-traumatic abdominal pain is typically evaluated by abdomino-pelvic computed tomography (CT) with oral and venous contrast. The accuracy of unenhanced CT for diagnosis in this setting has not been widely studied. OBJECTIVES: To assess the accuracy of unenhanced CT in establishing the etiology of acute non-traumatic abdominal pain. METHODS: We retrospectively reviewed the medical and imaging records of patients aged ≥ 18 years who presented to the emergency department (ED) during a 6-month period with acute non-traumatic abdominal pain of unknown etiology, and who were evaluated with non-contrast CT within 24 hours of ED admission. Clinical details were recorded. A presumptive clinical diagnosis and CT diagnosis were compared to the discharge diagnosis which was considered the reference standard. The requirement for informed consent was waived. RESULTS: Altogether, 315 patients met the inclusion criteria - 138 males (44%) and 177 females (56%); their mean age was 45 years (range 18-90). Clinical diagnosis correlated with the CT findings in 162 of the cases (51%). CT was accurate in 296/315 cases (94%). The leading diagnosis in cases of a mismatch between CT diagnosis and discharge diagnosis was infection mostly in the urinary tract (12/18). Sensitivity, specificity, positive predictive value and negative predictive value were 91%, 99%, 91% and 85% respectively. The discharge diagnosis was unchanged in the patients who returned to the ED within 1 week of the first admission. CONCLUSIONS: In this study, unenhanced CT proved to be a feasible, convenient and legitimate examination for the evaluation of patients with acute non-traumatic abdominal pain presenting to the ED.

Long-term outcomes of sigmoid diverticulitis: a single-center experience.

BACKGROUND: During the last decade, guidelines for the treatment of sigmoid diverticulitis have dramatically changed. The aim of this study is to report the long-term outcomes of patients treated for diverticulitis at a nonspecialized single center. MATERIALS AND METHODS: After obtaining institutional review board approval, medical records of all patients admitted to our institution with the diagnosis of sigmoid diverticulitis between 1998 and 2008 were reviewed. A follow-up of at least 5 years was required. RESULTS: During the study period, 266 patients were admitted to our hospital due to sigmoid diverticulitis with a mean follow-up period of 120 ± 2 months. Of the entire cohort, 249 patients (93.5%) were treated conservatively and 17 (6.5%) patients required emergent surgery on initial presentation. Patients treated conservatively (n = 249) encountered a median of two recurrent episodes (range 0-4). During follow-up, none of these patients required emergent surgery, and 27 patients (11%) underwent elective surgery for recurrent episodes (n = 24), chronic smoldering disease (n = 2), and fistula (n = 1). Minor and major complication rates after elective surgery were 18.5% and 30%, respectively. Specifically, four patients (15%) suffered an anastomotic leak (AL). Late complications after elective surgery occurred in 33% of patients including incisional hernias (11%), bowel obstruction (3.7%), anastomotic stenosis (3.7%), and recurrent diverticulitis (15%). CONCLUSIONS: Patients treated conservatively during their index admission for sigmoid diverticulitis do not require emergent surgery during long-term follow-up and the majority of patients (89%) do not require elective surgery. Elective sigmoidectomy at nonspecialized centers may result in high rates of recurrent diverticulitis (15%) and anastomotic leak (15%).

Respiratory manifestations in LPS-responsive beige-like anchor (LRBA) protein-deficient patients.

Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) protein deficiency is a rare syndrome of primary immune deficiency and immune dysregulation. In this study, we sought to summarize our experience with respiratory manifestations in LRBA-deficient patients. We conducted a retrospective analysis of the medical records of LRBA-deficient patients treated at Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Data retrieved included pulmonary workup, disease course, treatment, and outcome. Ten patients were included. Mean age at presentation of LRBA deficiency-related symptoms was 4.65 years (range 3 months-14 years). Respiratory symptoms were noted in six patients and consisted of chronic cough. Computed tomography revealed consolidation in five patients, atelectasis and bronchiectasis in two patients each, and diffuse interstitial lung disease in two additional patients. Respiratory tract cultures yielded a bacterial pathogen in five patients. Seven patients required active therapy: intravenous immunoglobulins (six patients), immunosuppressive drugs (five patients), and one was successfully treated with abatacept. Two patients underwent successful bone marrow transplantation. Mean follow-up period was 4.5 (range 0.4-14.4) years. On their latest examination, seven patients had no respiratory symptoms. CONCLUSION: Pulmonary manifestations are common in LRBA deficiency. Respiratory characteristics in LRBA-deficient patients should be investigated, monitored, and treated from the time of diagnosis. What is Known: • Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is a syndrome of primary immune deficiency and immune dysregulation. • Studies concerning the pulmonary characteristics of LRBA-deficient patients are lacking. What is New: • Respiratory manifestations include infections, bronchiectasis, interstitial lung disease, thoracic lymphadenopathy, and clubbing. • Awareness to pulmonary morbidity in LRBA-deficient patients and involvement of a pulmonologist in the workup and clinical decision-making is important. • Respiratory characteristics in LRBA-deficient patients should be investigated, monitored, and treated from a young age.

Mutations in EFL1, an SBDS partner, are associated with infantile pancytopenia, exocrine pancreatic insufficiency and skeletal anomalies in aShwachman-Diamond like syndrome.

BACKGROUND: For the final step of the maturation of the ribosome, the nascent 40S and 60S subunits are exported from the nucleus to the cell cytoplasm. To prevent premature association of these ribosomal subunits, eukaryotic initiation factor 6 (eIF6) binds the 60S subunit within the nucleus. Its release in the cytoplasm requires the interaction of EFL1 and SDBS proteins. In Shwachman-Diamond syndrome (SDS), a defective SDBS protein prevents eIF6 eviction, inhibiting its recycle to the nucleus and subsequent formation of the active 80S ribosome. OBJECTIVE: This study aims to identify the molecular basis of an SDS-like disease, manifested by pancytopenia, exocrine pancreatic insufficiency and skeletal abnormalities in six patients from three unrelated families. METHODS: Whole exome analysis was used for mutation identification. Fluorescence microscopy studies assessed the localisation of Tif6-GFP, the yeast eIF6 homologue, in yeast WT and mutant cells. Human and yeast EFL1 proteins, WT and mutants, were expressed in Saccharomyces cerevisiae BCY123 strain, and circular dichroism and small-angle X-ray scattering were used to assess the folding and flexibility of these proteins. Green malachite colorimetric assay was performed to determine the GTPase activity of WT and Efl1 mutants. RESULTS: Four patients were homozygous for p.R1095Q variant and two patients were homozygous for p.M882K variant in EFL1. Residue R1095 and M882 are conserved across species. Neither the GTPase activity of the mutant proteins nor its activation by the SDBD protein or the 60S ribosomal subunit were affected. Complementation of efl1Δ yeast cells with the EFL1 mutants rescued the slow growth phenotype. Nonetheless, Tif6-GFP was relocalised to the cytoplasm in mutant yeast cells in contrast to its nuclear localisation in WT cells. CONCLUSIONS: Mutations in EFL1 clinically manifest as SDS-like phenotype. Similar to the molecular pathology of SDS, mutant EFL1 proteins do not promote the release of cytoplasmic Tif6 from the 60S subunit, likely preventing the formation of mature ribosomes.

Delayed Laparoscopic Cholecystectomy for Acute Calculous Cholecystitis: Is it Time for a Change?

BACKGROUND: Our aim was to evaluate the advantages and limitations of delayed laparoscopic cholecystectomy (LC) in a tertiary center. MATERIALS AND METHODS: A retrospective analysis of all patients admitted to our institution with acute calculous cholecystitis (ACC) between January 2003 and December of 2012 was performed. Data collected included patient demographics and comorbidities, presenting symptoms, laboratory findings, imaging results, length of stay (LOS), time to surgery, and surgical complications. RESULTS: A total of 1078 patients were admitted with ACC. There were 593 females (55%), and the mean age was 57 ± 0.6 years. Mean LOS at initial admission, re-admission until surgery, and following surgery was 7.9 ± 0.2, 1.5 ± 0.1, and 3.4 ± 0.2 days, respectively. Percutaneous cholecystostomy (PC) tube was inserted in 24% of the patients. Only 640 (59%) patients eventually underwent LC. Mean time to surgery was 97 ± 9.8 days, and 16.4% of patients were readmitted in this time period resulting in a mean total LOS of 10.6 ± 0.2 days. Conversion rate to open surgery was 5.8% and bile duct injury occurred in 1.1%. Postoperative complications occurred in 9.8% of the patients, and 30-day mortality was 0.6%. Patients with more severe inflammation according to Tokyo Criteria grade were more likely to undergo PC, were more likely to be readmitted while waiting for LC, and also had more postoperative complications. CONCLUSIONS: Delayed LC is associated with significant loss of follow-up, long LOS, and higher than expected use of PC. Conversion rates are lower than in the literature while rates of bile duct injury and mortality are comparable. We believe these data as well as the available literature are sufficient to change our hospital policy regarding the surgical treatment of ACC from delayed to early same admission surgery in appropriate cases.

Characteristics of mesenteric lymphadenitis in comparison with those of acute appendicitis in children.

Mesenteric lymphadenitis (ML) is considered as one of the most common alternative diagnosis in a child with suspected acute appendicitis (AA). In this retrospective study, patients diagnosed with ML (n = 99) were compared in terms of demographic, clinical, and laboratory findings to patients diagnosed with AA (n = 102). This comparison was applied for both lymph nodes smaller and larger than 10 mm. When compared to patients with AA, patients with ML had significantly longer duration of symptoms prior to emergency department (ED) presentation (2.4 ± 2.6 vs 1.4 ± 1.4 days, P = 0.002) and multiple ED presentations (1.3 ± 0.7 vs 1.05 ± 0.3, P < 0.001) and had longer duration of stay in the ED (9.2 ± 5.9 vs 5.2 ± 4 h, P < 0.001), respectively. They also had significantly lower WBC (10.16 ± 4.7 × 103/dl vs 15.8 ± 4.4 × 103/dl, P < 0.001) with lymphocyte predominance (24.6 ± 14 vs 13 ± 8.7%, P < 0.001) and lower CRP levels (0.48 vs 1.6 mg/dl). Migration of pain (28 vs 7%), vomiting (62 vs 34%), and classic abdominal findings of AA (72 vs 20%) were all significantly more common for children with AA. When comparing lymph node size, no significant difference was found between those presenting with small and large nodes. CONCLUSION: This study highlights multiple clinical and laboratory findings that differentiate ML and AA. Moreover, the absence of any difference with regard to the lymph nodes size might suggest that lymph nodes enlargement is a non-specific finding. What is Known : • Mesenteric lymphadenitis is a very common diagnosis in children with suspected acute appendicitis. • Despite its prevalence, only few studies addressed the clinical characteristics of this clinical entity and their comparison with acute appendicitis. What is New: • Mesenteric lymphadenitis and acute appendicitis could be differentiated by multiple clinical and laboratory parameters. • No significant difference was found between those presenting with small and large lymph nodes.

Postmortem Computer Tomography Appearance of the Aortic Arch in Children: What Is Considered Normal?

BACKGROUND: Virtual autopsies by computer tomography (CT) or magnetic resonance imaging can be valuable in cases of unexplained infant death. The radiologist must be familiar with the normal appearance of all the segments of the thoracic aorta in normal and deceased children. A thorough review of the literature revealed no prior articles describing CT changes in the ascending aorta or the aortic arch in pediatric virtual autopsies. OBJECTIVES: To compare the CT appearance of the thoracic aorta in deceased children and in those younger than 3 years of age. METHODS: Hospital registries were searched for cases of unexpected deaths in children younger than 3 years old, with a postmortem CT available, as well as for clinically indicated chest CT in children of the same age during a 5 year period. The ascending aorta (AA), aortic arch (arch), and the descending aorta (DA) diameters were measured. Student's t-tests and Mann-Whitney U-tests were used to compare the two groups. RESULTS: A total of 64 scans were reviewed: 35 postmortem and 29 performed on living patients. The differences in the diameter and the ratios of the diameter between the AA and the arch, as well as between the arch and the DA in the postmortem and living groups were statistically significant (P < 0.05). CONCLUSIONS: On postmortem CT scans, we found focal tapering of the aortic caliber at the level of the arch between the origin of the brachiocephalic artery and left subclavian artery. This finding should not be misinterpreted as a hypoplastic aortic arch.

Association between renal cystic lesions and bilateral Wilms' tumours.

OBJECTIVES: Evaluate a potential association between Wilms' tumour (WT) and renal cystic lesions. METHODS: Digital records and imaging files of consecutive patients diagnosed with WT between 2004 and 2014 were retrospectively reviewed under an Institutional Review Board waiver of informed consent. The locations of renal cysts seen on US, CT, and/or MRI were recorded and compared with the locations of newly developed WT. RESULTS: A total of 48 patients (mean age 3 years 9 months) presented with newly diagnosed WT in the study period. Mean follow-up was 4.5 (range 1-10) years. WT was unilateral in 40 children, bilateral in 8. Renal cysts were identified in only one of the forty patients (2.5 %) with unilateral disease - in the contralateral kidney. In contrast, renal cysts were found in seven of eight patients with bilateral WT (87.5 %), in two of whom, new tumours developed in the same location where cysts had been seen on previous imaging studies. CONCLUSIONS: Renal cystic lesions in patients with Wilms' tumour should be regarded as potential tumour precursors, and followed with frequent imaging. KEY POINTS: • Cortical renal cystic lesions have a high association with bilateral Wilms' tumour. • In children with Wilms' tumour renal cysts are possible tumour precursors. • MRI appears to be the best modality in depicting the cortical cysts.

Extending the Spectrum of Radiological Findings in Patients With Severe Osteopetrosis and Different Genetic Backgrounds.

PURPOSE: To evaluate radiological findings in a cohort of 22 patients with infantile malignant osteopetrosis in order to establish the correlation between radiological findings and different genetic backgrounds. MATERIALS AND METHODS: Clinical files, genetic analysis results, and radiological examinations of children treated for osteopetrosis with bone marrow transplantation in a referral center in the last 5 years were retrospectively evaluated. The study received institutional review board (IRB) approval. RESULTS: Twenty-two patients were included in the study: 18 males, four females, ages 1 month-9 years 10 months, and the median age was 11 months (mean 23 months). There were 12 patients with different mutations in the TCIRG1 gene, five with mutations in the SNX10 gene, four children harbored RANK mutations, and one patient had a CLCN7 mutation. We noted more severe radiological findings in patients with TCIRG1 and RANK mutations, including fractures, osteopetrorickets, hydrocephalus, and hepatomegaly. Varus deformity of the femoral neck was seen exclusively in patients with a TCIRG1 mutation. CONCLUSIONS: The variable genetic spectrum of osteopetrosis is associated with a variable radiological presentation. These correlations may be helpful for priorities in genetic analysis.

Improved Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Infantile Malignant Osteopetrosis Using Fludarabine-Based Conditioning.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for infantile malignant osteopetrosis (IMO), but is associated with a high incidence of adverse outcomes. In this study, we present our experience with HSCT for IMO patients comparing different types of conditioning regimens. METHODS: Thirty-eight patients with IMO (aged from 1 month to 6 years, median 0.66 years) who underwent allogeneic HSCT from 1983 in our hospital were included in this retrospective study. Fludarabine-based conditioning regimens were used in 26 patients and 12 patients were transplanted using other conditioning regimens. RESULTS: The overall survival after conditioning with fludarabine was 96% (25/26) versus 58% (7/12) for the alternative regimens (P = 0.004), with significantly fewer adverse effects including hypercalcemia and veno-occlusive disease of liver. All patients who survive are clinically well. CONCLUSIONS: We conclude that fludarabine-based conditioning regimens are safe and effective in patients with IMO, improving morbidity and mortality related to HSCT.

Diagnostic value of CT compared to ultrasound in the evaluation of acute abdominal pain in children younger than 10 years old.

To assess the diagnostic value of ultrasound compared to CT in evaluating acute abdominal pain of different causes in children 10 years of age and under, hospital records and imaging files of 4052 patients under age of 10 who had imaging for abdominal pain were reviewed. One-hundred-thirty-two patients (3 %), (74 males/58 females) who underwent ultrasound and CT within 24 h were divided by age: group I, ages 0-48 months (25 patients); group II, 49-84 months (53 patients); and group III, 85-120 months (54 patients). Diagnoses at ultrasound, CT, and discharge were compared. Cases of a change in diagnosis following CT and impact of the changed diagnosis on patient management were assessed. Non-diagnostic ultrasound or a diagnostic conundrum was present in a small percentage (3 %) of our patients. In the group of patients imaged with two modalities, CT changed the diagnosis in 73/132 patients (55.3 %). Patient management changed in 63/132 patients (47.7 %). CT changed the diagnosis in 46/64 patients with surgical conditions (71.8 %, p < 0.001). Among patients with surgical conditions, the difference between ultrasonography (US) and CT diagnoses was significant in groups 2 (p = 0.046) and 3 (p = .001). The impact of the change in diagnosis in surgical patients imaged with two modalities was significant in the group as a whole and in each age group separately. Non-diagnostic or equivocal US in a small percentage of patients is probably sufficient to justify the additional radiation burden.

CT differentiation between tubo-ovarian and appendiceal origin of right lower quadrant abscess: CT, clinical, and laboratory correlation.

To investigate which clinical, laboratory, and CT findings potentially facilitate the differential diagnosis between tubo-ovarian abscess (TOA) and periappendicular abscess (PAA), we retrospectively reviewed abdominal CT examinations and medical records for all women who presented to our medical center with unilateral right pelvic abscess formation who underwent CT evaluation from 2004-2014. A wide spectrum of clinical data and imaging findings were recorded. CT diagnoses were made in consensus by two experienced body radiologists blinded to the final diagnosis. Findings associated with the infections were compared using the chi-square (χ(2)) or the Fisher exact test. Ninety-one patients were included; 58 with PAA (mean age 46 years) and 33 with TOA (mean age 37 years). Pain on cervical motion (67 %) and vaginal discharge (21 %) were significantly more common in TOA; other clinical signs were similar. The presence of right ovarian vein entering the mass on CT had 100 % specificity and 94 % sensitivity to TOA. Distended right fallopian tube (79 %), mass posterior to mesovarium (76 %), contralateral pelvic fat stranding (55 %), and thickening of sacrouterine ligaments (55 %) were significantly more common in TOA. Positive "arrowhead sign" (91 %), mesenteric lymphadenopathy (85 %), small bowel wall thickening (55 %), fluid in the right paracolic gutter (50 %), and cecal wall thickening (48 %) were significantly more common in PAA;internal gas was revealed only in PAA (33 %). Distinct CT features can increase diagnostic certainty regarding the origin of right lower quadrant abscess in women.

The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy.

Severe congenital neutropenia as well as primary myelofibrosis are rare in infancy. Elucidation of the underlying mechanism is important because it extends our understanding of the more common adult forms of these disorders. Using homozygosity mapping followed by exome sequencing, we identified a Thr224Asn mutation in the VPS45 gene in infants from consanguineous families who suffered from life-threatening neutropenia, which was refractory to granulocyte CSF, from defective platelet aggregation and myelofibrosis. The mutation segregated in the families, was not present in controls, affected a highly conserved codon, and apparently destabilized the Vps45 protein, which was reduced in the patients' leukocytes. Introduction of the corresponding mutation into yeast resulted in reduced cellular levels of Vps45 and also of the cognate syntaxin Tlg2, which is required for membrane traffic through the endosomal system. A defect in the endosomal-lysosomal pathway, the homologous system in humans, was suggested by the absence of lysosomes in the patients' fibroblasts and by the depletion of α granules in their platelets. Importantly, accelerated apoptosis was observed in the patients' neutrophils and bone marrow. This is the first report of a Vps45-related disease in humans, manifesting by neutropenia, thrombasthenia, myelofibrosis, and progressive bone marrow failure.