Acute pancreatitis in pancreatic-insufficient cystic fibrosis patients treated with CFTR modulators.

Cystic fibrosis transmembrane conductance regulator modulator therapy is associated with substantial clinical benefit and improved quality of life in patients with cystic fibrosis (CF). While their effect on lung function has been clearly reported, we are still in the process of unraveling the full impact they have on the pancreas. We present two cases of pancreatic-insufficient CF patients who presented with acute pancreatitis shortly after commencing elexacaftor/tezacaftor/ivacaftor modulator therapy. Both patients were treated with ivacaftor for 5 years prior to elexacaftor/tezacaftor/ivacaftor initiation, but had no previous episodes of acute pancreatitis. We suggest that highly effective modulator combination therapy may restore additional pancreatic acinar activity, resulting in the development of acute pancreatitis in the interim until ductal flow is improved. This report adds to the growing evidence for possible restoration of pancreatic function in patients receiving modulator therapy, and highlights that treatment with elexacaftor/tezacaftor/ivacaftor may be associated with acute pancreatitis until ductal flow is restored, even in pancreatic-insufficient CF patients.

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.

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%.

Clinical presentation and analysis of genotype-phenotype correlations in patients with malignant infantile osteopetrosis.

Malignant infantile osteopetrosis (MIOP) is the autosomal recessive, severe form of osteopetrosis. This rare genetic syndrome usually presents soon after birth and is often fatal if left untreated. Early diagnosis is key for proper management but clinical presentation is diverse, and oftentimes diagnosis may be challenging. In this study, we retrospectively collected data of genetic mutations and phenotypic characteristics at the initial presentation of 81 MIOP patients and analyzed genotype-phenotype correlations. The most common genetic mutation was in the TCIRG1 gene (n = 46, 56.8%), followed by SNX10 (n = 20, 25%). Other genetic mutations included RANK (n = 7, 8.7%), CLCN7 (n = 5, 6.2%) and CA2 (n = 3, 3.7%). More than half of the patients presented with growth retardation (n = 46, 56.8%). Twenty-one of the patients were blind (26%) and thirty-seven patients had other neurological deficits (45.7%) at the time of initial presentation. Most patients presented with hematological signs of bone marrow failure including anemia (n = 69, 85.2%) and thrombocytopenia (n = 33, 40.7%). Thrombocytopenia at initial presentation was significantly more prevalent in patients with mutations in the TCIRG1 gene (p = 0.036). Other phenotypic presenting features were not found to be significantly correlated to specific gene mutations. In conclusion, the initial presentation of MIOP is variable, but some features are common such as growth retardation, visual impairment, and cytopenias. High awareness of MIOP presenting signs is essential for prompt diagnosis of this challenging 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.

How abnormal is the normal? Clinical characteristics of CF patients with normal FEV1.

BACKGROUND: Normal values (>80%) of Forced Expiratory Volume in one second (FEV1 ) in patients with cystic fibrosis (CF) may lead to the interpretation that there is no lung disease. This study is a comprehensive analysis of lung involvement in CF patients having normal FEV1 . METHODS: Patients were recruited from two CF centers: Hadassah Medical Center, Jerusalem and Vall d' Hebron Hospital, Barcelona. Lung disease was assessed by lung clearance index (LCI), chest CT-Brody score, respiratory cultures, number of pulmonary exacerbations (PEx), and days of antibiotic treatment in the year before the assessment. RESULTS: Of the 247 patients, 89 (36%) had FEV1 ≥80% and were included in the study (mean age, 17.6; range, 4.25-49 years). Chronic Pseudomonas aeruginosa infection was found in 21%, and 31% had at least one major PEx in the year before the study. Abnormally elevated LCI was found in 86% of patients, ranging between 7.52 and 18.97, and total Brody score (TBS) was abnormal in 92% (range, 5.0-96.5). Patients with chronic P. aeruginosa had significantly higher LCI (p = .01) and TBS (p = .02) which were associated with more major PEx (p < .01 and p = .01, respectively) and more days of intravenous (IV) antibiotic treatment in the preceding year (p = .03 and p = .001, respectively). CONCLUSIONS: Most CF patients with normal FEV1 have already physiological and structural lung abnormalities which were associated with more PEx and IV antibiotic treatment. Further studies are needed to determine if better adherence to the currently used therapies and the new cystic fibrosis transmembrane modulators will prevent the progression of lung disease.

Lymphadenopathy Associated With the COVID-19 Vaccine.

The coronavirus disease 2019 (COVID-19) pandemic has dominated nearly everyone's life since its initial outbreak in the Hubei province of China in December 2019. The disease had spread quickly throughout the world causing extensive, widespread morbidity, over two million deaths, and economical and social devastation over the entire world. Researchers and pharmaceutical companies around the globe have been racing to develop potent and safe vaccines for the disease. Pfizer-BioNTech COVID-19 vaccine followed by Moderna COVID-19 mRNA-1273 vaccine were the first to receive FDA approval. These vaccines are based on messenger RNA novel technology and considered efficient in preventing contagion ensuring safety. Known side effects for this vaccine have been reported as very similar to those known for other vaccines. Specifically, lymphadenopathy has not been considered a common manifestation of COVID-19 vaccination. Israel has been cited as leading in the introduction of these vaccines, which are available for every citizen older than 16 years. Here, we present the cases of three patients who developed lymphadenopathy after the first dose of Pfizer-BioNTech COVID-19 vaccine. Time elapsed from the injection until the appearance of the enlarged nodes, clinical symptoms, and sonographic features differed between the patients, but in all cases gradual regression was noted in the enlarged nodes until complete resolution. Accordingly, to our knowledge, this is the first report describing post-COVID-19 vaccine lymphadenopathy detailing the clinical aspects, sonographic features, and outcomes.

Opportunistic screening for osteoporosis and osteopenia by routine computed tomography scan: A heterogeneous, multiethnic, middle-eastern population validation study.

PURPOSE: We aimed define thresholds for HU values observed on opportunistic CT scans that suggest abnormal bone mineral density (BMD) in a heterogeneous Middle Eastern population. METHODS: Consecutive patients who had undergone CT and dual-energy X-ray absorptiometry (DXA) test of the lumbar spine within 6 months were included in this retrospective study. Hounsfield units (HU) on lateral lumbar spine CT and BMD at the spine and hip on DXA were compared. Potential HU thresholds suggestive of abnormal BMD were established using receiver operating characteristic (ROC) analysis. RESULTS: 246 patients (mean age of 64 ±â€¯11.6 years; 83 % female) were included. On DXA, 27 % had osteoporosis, 56 % had osteopenia, and 17 % had normal BMD. To distinguish osteoporosis from non-osteoporosis (osteopenia, normal BMD), a threshold of HU160 had sensitivity 95 % and the balanced threshold was HU121 (sensitivity 74 %, specificity 61 %). To distinguish normal from abnormal BMD (osteoporosis, osteopenia), a threshold of HU110 had specificity 93 % and the balanced threshold was HU149 (sensitivity 76 %, specificity 74 %). CONCLUSIONS: In a heterogeneous Middle-Eastern population, our study supports the reported correlation between HU values on lumbar spine CT and BMD on DXA. In this population, HU > 160 correlates with low probability of osteoporosis on DXA, and screening examination is not warranted unless a vertebral fracture is detected; for HU ≤ 110 there is high probability of abnormal (osteoporosis or osteopenia) BMD, DXA examination is warranted; Finally, for HU 110-160, there is an intermediate chance of abnormal BMD, DXA examination may be warranted in specific patients with other risk factors.

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.

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.

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.

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.

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%).

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.

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.

Comparison of Appendectomy Outcomes Between Senior General Surgeons and General Surgery Residents.

Importance: In some centers, the presence of a senior general surgeon (SGS) is obligatory in every procedure, including appendectomy, while in others it is not. There is a relative paucity in the literature of reports comparing the outcomes of appendectomies performed by unsupervised general surgery residents (GSRs) with those performed in the presence of an SGS. Objective: To compare the outcomes of appendectomies performed by SGSs with those performed by GSRs. Design, Setting, and Participants: A retrospective analysis was performed of all patients 16 years or older operated on for assumed acute appendicitis between January 1, 2008, and December 31, 2015. The cohort study compared appendectomies performed by SGSs and GSRs in the general surgical department of a teaching hospital. Main Outcomes and Measures: The primary outcome measured was the postoperative early and late complication rates. Secondary outcomes included time from emergency department to operating room, length of surgery, surgical technique (open or laparoscopic), use of laparoscopic staplers, and overall duration of postoperative antibiotic treatment. Results: Among 1649 appendectomy procedures (mean [SD] patient age, 33.7 [13.3] years; 612 female [37.1%]), 1101 were performed by SGSs and 548 by GSRs. Analysis demonstrated no significant difference between the SGS group and the GSR group in overall postoperative early and late complication rates, the use of imaging techniques, time from emergency department to operating room, percentage of complicated appendicitis, postoperative length of hospital stay, and overall duration of postoperative antibiotic treatment. However, length of surgery was significantly shorter in the SGS group than in the GSR group (mean [SD], 39.9 [20.9] vs 48.6 [20.2] minutes; P < .001). Conclusions and Relevance: This study demonstrates that unsupervised surgical residents may safely perform appendectomies, with no difference in postoperative early and late complication rates compared with those performed in the presence of an SGS.

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.