Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human-derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation-related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs.

Nipple-Sparing Mastectomy and Adequate Margins for Patients With Ductal Carcinoma In Situ.

BACKGROUND: For patients with ductal carcinoma in situ (DCIS) undergoing breast conservation surgery (BCS), guidelines advise a margin width of at least 2 mm, with studies demonstrating decreased recurrence risk compared to narrower margins. However, limited data exist establishing if this margin is appropriate in mastectomies, and specifically for nipple-sparing mastectomy (NSM). Consequently, we evaluated the margins of DCIS patients undergoing NSM and resulting oncologic outcomes. METHODS: A single-institution retrospective review was performed in patients with DCIS or DCIS with microinvasion (DCIS + MI) undergoing NSM from April 2010 to December 2021. Patient and tumor characteristics, margin status, treatment, and outcomes information were collected. The association between margins and local-regional (LRR) and distant recurrence (DR) were examined. RESULTS: 161 patients were included, comprising 284 NSM (164 therapeutic, 120 prophylactic). 153 patients had DCIS and 8 had DCIS + MI. Most patients had hormone sensitive, 123 (76.4%), and nuclear grade 2, 72 (44.7%), disease. In total, 35 (21.7%) patients had positive or <2 mm margins. Of these, 21 (60%) involved the anterior margin. At a median follow-up of 45 months (range 0-151), 2.5% (n = 4) had a LRR and .6% (n = 1) had a DR. Of patients with a recurrence, only 2 had positive or <2 mm margins, 1 had received endocrine therapy, and none received adjuvant radiation. DISCUSSION: No specific margin status was found to correlate with recurrence for patients with DCIS or DCIS + MI undergoing NSM, with an altogether low recurrence risk. Overall, this suggests that recommended DCIS margins in BCS doesn't necessarily apply in NSM, where margins of <2 mm may be acceptable.

User-Centered Development of HEARTPrep, a Digital Health Psychosocial Intervention for Prenatally Diagnosed Congenital Heart Disease.

User-centered models for the development of digital health interventions are not consistently applied in healthcare settings. This study used a five-phase, user-centered approach to develop HEARTPrep©, a psychosocial intervention delivered via mobile app and telehealth to mothers expecting a baby with congenital heart disease (CHD) to promote maternal, family, and child well-being. Phases of intervention development were: (I) establishing partnerships; (II) creating content; (III) developing prototype and testable intervention; (IV) conducting think-aloud testing; and (V) completing beta testing. Partnerships with parents, clinicians, and design/technology experts were integral throughout the development of HEARTPrep©. Parents of children with CHD also served as participants in Phases II-V, contributing to the creation of content and providing feedback to inform the iterative refinement of HEARTPrep©. These five phases produced a refined digital health intervention with promising feasibility, usability, and acceptability results. This user-centered approach can be used to develop digital health interventions targeting various health outcomes.

Does the atrial incision affect rates of early postoperative atrial arrhythmias in mitral valve surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'in patients undergoing mitral valve surgery, does atrial incision affect early postoperative rates of atrial arrhythmia'. Two hundred and four papers were found. Nine represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Data suggest that a transeptal incision is associated with increased rates of postoperative atrial arrhythmia compared with direct left atriotomy.

Divided stimulus control depends on differential and nondifferential reinforcement: Testing a quantitative model.

We investigated the effects of differential and nondifferential reinforcers on divided control by compound-stimulus dimensions. Six pigeons responded in a delayed matching-to-sample procedure in which a blue or yellow sample stimulus flashed on/off at a fast or slow rate, and subjects reported its color or alternation frequency. The dimension to report was unsignaled (Phase 1) or signaled (Phase 2). Correct responses were reinforced with a probability of .70, and the probability of reinforcers for errors varied across conditions. Comparison choice depended on reinforcer ratios for correct and incorrect responding; as the frequency of error reinforcers according to a dimension increased, control (measured by log d) by that dimension decreased and control by the other dimension increased. Davison and Nevin's (1999) model described data when the dimension to report was unsignaled, whereas model fits were poorer when it was signaled, perhaps due to carryover between conditions. We are the first to test this quantitative model of divided control with reinforcers for errors and when the dimension to report is signaled; hence, further research is needed to establish the model's generality. We question whether divided stimulus control is dimensional and suggest it may instead reflect joint control by compound stimuli and reinforcer ratios.

Virtually Delivered Psychosocial Intervention for Prenatally Diagnosed Congenital Heart Disease: Feasibility and Acceptability of HEARTPrep.

Prenatal diagnosis of congenital heart disease (CHD) often leads to anxiety, depression, and traumatic stress in expectant mothers, with long-term implications for the child and family. However, psychosocial intervention is rarely incorporated into prenatal care. HEARTPrep is a virtually delivered psychosocial intervention aimed at reducing distress and social isolation and increasing parenting self-efficacy and hope for mothers expecting a baby with CHD to promote long-term child/family well-being. This study evaluated the feasibility and acceptability of HEARTPrep. Participants were mothers receiving cardiology care for a fetal CHD diagnosis. Partners could participate with the mother. HEARTPrep was delivered through a mobile app and telehealth. Feasibility was assessed through enrollment/retention rates. Acceptability was assessed through 20 Likert-scale and five open-ended questions. Of 39 recruited mothers, 35 (90%) enrolled. Half of partners (48%) also participated. Twenty-seven of 35 enrolled mothers (77%) completed HEARTPrep. On a scale from 0 (Not at All) to 4 (Very), mean item acceptability scores ranged from 3.5 to 3.9. Mothers reported HEARTPrep helped them feel less distressed (mean: 3.74), less alone (3.84), more prepared (3.89), and more hopeful (3.84). Opportunities to process emotions, develop coping skills, learn with their partner, navigate relationships, understand they are not alone, connect with peer support, access resources, and prepare for stressors were described as helpful. HEARTPrep is feasible and acceptable for mothers expecting a baby with CHD. Future research will evaluate its efficacy in preventing/reducing maternal mental health problems and improving postnatal clinical outcomes.

An atypical presentation of endometrial cancer as angina secondary to critically low hemoglobin and iron deficiency associated pancytopenia: A case report.

Endometrial cancer is the most common type of gynaecological cancer in high-income countries. Abnormal uterine bleeding (AUB) is the most common symptom of endometrial cancer; however, patients can often present in an atypical fashion. This case is an example of an atypical presentation of endometrial cancer, with angina secondary to severe iron deficiency anemia, and a rare example of pancytopenia secondary to iron deficiency. A 46-year-old nulliparous woman with no past medical history presented to the emergency department with acute chest pain. All her vitals were normal. The ECG showed T-wave inversion with a negative serum troponin. She had obvious pallor but appeared well. She had a critical hemoglobin of 1.9 g/dL and severe iron deficiency with a plasma iron level of <2 µg/L. In the 6 months leading up to her presentation, she had heavy and prolonged menstruation of up to 10 days. She received a total of 6 units of packed red blood cells and an iron infusion. Her chest pain resolved, and her pancytopenia corrected following replenishment of iron stores. She underwent a laparoscopic total hysterectomy, bilateral salpingo-oophorectomy for stage 1b, grade 2 endometroid adenocarcinoma. This is one of the lowest hemoglobin levels recorded in a hemodynamically stable patient with endometrial cancer, and the only case report of iron deficiency induced pancytopenia secondary to abnormal uterine bleeding. This case is a reminder that female patients with angina should have their hemoglobin checked, and patients with anemia should have a thorough review of their gynaecological history.

Hereditary renal cancer patient and public involvement group: A collaborative, consensus decision process to develop a communication tool for patient use.

Patient and public involvement (PPI) must be more frequently embedded within clinical research to ensure translational outcomes are patient-led and meet patient needs. Active partnerships with patients and public groups are an important opportunity to hear patient voices, understand patient needs, and inform future research avenues. A hereditary renal cancer (HRC) PPI group was developed with the efforts of patient participants (n = 9), pooled from recruits within the early detection for HRC pilot study, working in collaboration with researchers and healthcare professionals (n = 8). Patient participants had HRC conditions including Von Hippel-Lindau (n = 3) and Hereditary Leiomyomatosis and Renal Cell Carcinoma (n = 5), and public participants included two patient Trustees (n = 2) from VHL UK & Ireland Charity. Discussions among the enthusiastic participants guided the development of a novel patient information sheet for HRC patients. This communication tool was designed to aid patients when informing family members about their diagnoses and the wider implications for relatives, a gap identified by participants within group discussions. While this partnership was tailored for a specific HRC patient and public group, the process implemented can be employed for other hereditary cancer groups and could be transferable within other healthcare settings.

Is superstitious responding a matter of detectability? A replication of Killeen (1978).

Organisms may sometimes behave as if a contingency exists between behavior and consequences, even if this is not actually the case. Killeen (1978) suggested that such superstition occurs because of factors that bias subjects to behave "superstitiously" rather than because of failures of discrimination. We systematically replicated Killeen's experiment and compared contingency discrimination between different consequences. Six pigeons responded in a matching-to-sample procedure in which a response-independent or response-dependent stimulus change, food delivery, or blackout occurred. The pigeons reported whether the consequence was response dependent or response independent by choosing between two side keys. Discrimination was strongest after stimulus changes, weaker after blackouts, and weakest after food deliveries. These differences persisted even after additional training, suggesting asymmetries that may reflect differences in the disruptive effects of different consequences on remembering and/or behavioral mnemonics. Importantly, the pigeons were not biased to report response-dependent consequences unless that response was consistent with locational biases; that is, they behaved "superstitiously" when there was a reason to be biased to do so. These findings corroborate Killeen's and demonstrate that behavior may deviate from contingencies not necessarily because subjects cannot discriminate those contingencies but because they are biased to behave otherwise.

The relationship between personal and interpersonal mental health experiences and stigma-related outcomes in Hong Kong.

BACKGROUND: Previous research indicates that personal mental health experiences (e.g. one's current mental health status) and interpersonal mental health experiences (e.g. one's familiarity with someone with mental illness) are associated with stigma-related outcomes. These outcomes include knowledge, attitudes and desire for social distance from people with mental illness. AIMS: To explore the extent to which current personal mental health status and familiarity with mental illness predict stigma-related outcomes in Hong Kong. METHOD: Data were drawn from a larger research project examining mental well-being in Hong Kong citizens. Citizens (N = 1010) aged ≥18 years were surveyed between August and September 2021. RESULTS: Multiple regression analyses revealed that immediate family and friends showed better attitudinal outcomes and lower desire for social distance compared with people who did not know anyone with mental illness (all ß > 1.00, all P < 0.05), whereas people with personal experience of mental illness showed higher prejudicial attitudes compared with people who did not know anyone with mental illness (ß = -0.744, P = 0.016). Better current personal mental health predicted lower prejudicial attitudes (ß = 0.488, P < 0.001) and mixed outcomes on different realms of mental health knowledge. CONCLUSIONS: Cultural concerns surrounding 'saving face' and emphasis on collectivistic values may explain the nonlinear relationship between personal and interpersonal mental health experiences and stigma-related outcomes. Future anti-stigma interventions should tailor their approaches to the needs of people with different levels of familiarity with mental illness and include efforts to support the mental health of the overall population.

Revaluation of overselected stimuli: Emergence of control by underselected stimuli depends on degree of overselectivity.

Stimulus overselectivity describes strong control by one stimulus element at the expense of other equally relevant elements. Research suggests that control by underselected stimuli emerges following extinction of the overselected stimulus ("revaluation") and the emergence is larger when overselectivity is greater. We compared such revaluation effects with a control compound or condition in two experiments. Human participants chose between compound S+ and S- stimuli. Then, to assess control by compound-stimulus elements, participants chose between individual elements in a testing phase without feedback. The S+ element chosen most often (the overselected element) underwent revaluation, during which choice of that element was extinguished and choice of a novel element reinforced. Thereafter, participants completed a retesting phase. Revaluation reduced choice of the overselected element. Choice of the underselected element decreased for participants with low overselectivity but increased for participants with high overselectivity. This was not the case for a control compound that did not undergo revaluation (Experiments 1 and 2) or in a control condition in which the overselected element continued to be reinforced during revaluation (Experiment 2). These findings suggest that overselectivity levels may modulate revaluation effects, and they also highlight the importance of the contingency change in postrevaluation changes in stimulus control.

SOFTLY: Comparison of outcomes of rigid versus soft collar during emergency department investigation for potential cervical spine injury in low-risk blunt trauma patients - A pilot study.

OBJECTIVE: Blunt trauma patients with potential cervical spine injury are traditionally immobilised in rigid collars. Recently, this has been challenged. The present study's objective was comparison of the rate of patient-oriented adverse events in stable, alert, low-risk patients with potential cervical spine injuries immobilised in rigid versus soft collars. METHODS: Unblinded, prospective quasi-randomised clinical trial of neurologically intact, adult, blunt trauma patients assessed as having potential cervical spine injury. Patients were randomised to collar type. All other aspects of care were unchanged. Primary outcome was patient-reported discomfort related to neck immobilisation by collar type. Secondary outcomes included adverse neurological events, agitation and clinically important cervical spine injuries (clinical trial registration number: ACTRN12621000286842). RESULTS: A total of 137 patients were enrolled: 59 patients allocated to a rigid collar and 78 to a soft collar. Most injuries were from a fall <1 m (54%) or a motor vehicle crash (21.9%). Median neck pain score of collar immobilisation was lower in the soft collar group (3.0 [interquartile range 0-6.1] vs 6.0 [interquartile range 3-8.8], P < 0.001). The proportion of patients with clinician-identified agitation was lower in the soft collar group (5% vs 17%, P = 0.04). There were four clinically important cervical spine injuries (two in each group). All were treated conservatively. There were no adverse neurological events. CONCLUSIONS: Use of soft rather than rigid collar immobilisation for low-risk blunt trauma patients with potential cervical spine injury is significantly less painful for patients and results in less agitation. A larger study is needed to determine the safety of this approach or whether collars are required at all.

ABC/2 formula for "bedside" postoperative pneumocephalus volume measurement.

BACKGROUND: Postoperative pneumocephalus is associated with a higher risk of recurrence of chronic subdural hematoma (cSDH). However, there is no verified simple way to measure the pneumocephalus volume at the bedside for daily clinical use. The ABC/2 method was shown to be a simple and reliable technique to estimate volumes of intracranial lesions, such as intracranial hematomas. This study aims to evaluate the accuracy of the ABC/2 formula in estimating volumes of pneumocephalus, as compared to the gold standard with computer-assisted volumetric analysis. METHODS: A total of 141 postoperative computed tomographic (CT) brain scans of cSDH patients with burr-hole drainage were analysed. Pneumocephalus volume was measured independently by both the ABC/2 formula and the computer-assisted volumetric measurement. For the computer-assisted measurement, the volume of the air was semiautomatically segmented and calculated by computer software. Linear regression was used to determine the correlation between the ABC/2 method and computer-assisted measurement. RESULTS: The postoperative pneumocephalus volume after bilateral burr-hole drainage was significantly larger than that of unilateral burr-hole drainage (29.34 ml versus 12.21 ml, p < 0.001). The estimated volumes by the formula ABC/2 significantly correlated to the volumes as measured by the computer-assisted volumetric technique, with r = 0.992 (p < 0.001). The Pearson correlation coefficient is very close to 1, which signifies a very strong positive correlation, and it is statistically significant. CONCLUSIONS: An excellent correlation is observed between the ABC/2 method and the computer-assisted measurement. This study verified that the ABC/2 method is an accurate and simple "bedside" technique to estimate pneumocephalus volume.

Univariate and Multivariable Analyses on Independent Predictors for Cervical Spinal Injury in Patients with Head Injury.

OBJECTIVE: This study aims to identify independent factors associated with cervical spinal injuries in head-injured patients. The extent of injuries to other body parts was assessed by the Abbreviated Injury Scale (AIS) and was included in the analysis. METHODS: Consecutive head-injured patients admitted via the emergency department from January 1, 2014 to December 31, 2016 were retrospectively reviewed. The inclusion criteria were head-injured patients with an Abbreviated Injury Scale (AIS) score ≥2 (i.e., head injuries with intracranial hematoma or skull fracture). Patients with minor head injuries with only scalp abrasions or superficial lacerations without significant intracranial injuries (i.e., head injury AIS score = 1) were excluded. The primary outcome was to identify independent predictors associated with cervical spinal injuries in these head-injured patients. Univariate and multivariable analyses were conducted. RESULTS: A total of 1105 patients were identified. Of these patients, 11.2% (n = 124) had cervical spinal injuries. Univariate and multivariable analyses identified male gender (P = 0.006), the presence of thoracic injury (including rib fracture, hemothorax, or pneumothorax) (P = 0.010), and hypotension with systolic blood pressure <90 mm Hg on admission (P = 0.009) as independent predictors for cervical spinal injury in head-injured patients. CONCLUSIONS: This study showed that about 1 in 10 patients with significant head injury had cervical spine injury, usually associated with fracture or dislocation. Male gender, the presence of thoracic injury, and hypotension on admission were independent risk factors associated with cervical spinal injuries.

Measurement of aspiration pressure in cannula brain tumour biopsy and its correlation with ultrasonographic elastography.

BACKGROUND: Stereotactic brain biopsy is to perform the manual aspiration tissue biopsy using a cannula on a syringe under stereotactic guidance to provide histological confirmation. Excessive vacuum aspiration increases the risk of haemorrhage. Manual aspiration relies on the surgeon's experience while the minimum vacuum pressure is unknown. OBJECTIVES: 1. To assess the aspiration vacuum pressure range in cannula brain tumour biopsy; 2. To understand the correlation of ultrasound elastography data with the aspiration pressure. METHODS: This prospective study has recruited 10 patients for stereotactic brain tumour biopsy. With the use of ultrasound elastography, strain ratio of the lesion was assessed in real time before biopsy. Vacuum aspiration pressures were recorded using a T-connector pressure sensor during the stereotactic biopsy. RESULTS: A total of 11 biopsies were taken from 10 patients, including a bilateral biopsy for a patient with bifrontal lesions. The diagnostic yield was 100% in all the 10 patients with no symptomatic haemorrhage (but 2 subclinical haemorrhages in CT scan) nor infection. The vacuum pressures ranged from 40.34 to 65.61 kPa and the strain-ratio ranged from 0.405 to 2.74. Strain ratio of the lesion at the lower range required a lower range of aspiration pressure, whereas lesions of Strain ratio over 0.45 required a higher range of aspiration pressure. CONCLUSION: A vacuum pressure of 40 to 66 kPas is safe and adequate for biopsy of various types of tumours with heterogenous elastographic characters. Ultrasonographic elastography may be a real-time guide for the minimum vacuum pressure required for biopsy.

Effects of brief post-sample cues signaling presence or absence of reinforcers in delayed matching-to-sample.

When short-term memory is assessed in the delayed matching-to-sample (DMTS) procedure, performance is better when cues signal larger reinforcer magnitudes or higher reinforcer probabilities for correct responding. Previous studies demonstrating signaled-magnitude or signaled-probability effects presented cues for a prolonged period during the sample stimulus and/or retention interval. The present study asked whether a signaled-probability effect would occur with brief post-sample cues that signaled the presence or absence of reinforcement. Five pigeons responded in a DMTS task in which sample stimuli were sometimes followed by a 0.5-s cue signaling that reinforcers would either be available or not available in the current trial, and the retention interval varied from 0.5 s to 20 s. A reliable signaled-probability effect was found when reinforcers were arranged independently and for all correct responses, whereas a smaller, less systematic effect was found when reinforcers were arranged dependently and probabilistically. These findings highlight the importance of reinforcement contingencies and contingency discriminability in remembering, and add to the evidence showing that cues signaling differential reinforcement in DMTS may affect processes during the retention interval and comparison phase, rather than attention to the sample stimulus.

Bringing the past into the present: Control by exteroceptive stimuli and key-peck location in a concurrent-chains procedure.

We recently found that initial-link stimuli signaling trial outcomes (signals) in a concurrent-chains procedure exerted imperfect control during initial and terminal links. Here, we conducted a follow-up experiment to investigate further such imperfect control. Five pigeons worked on a concurrent-chains procedure in which one alternative led to a terminal link ending in a smaller-sooner reinforcer delivery, and the other in a larger-later reinforcer. During initial links of some trials, compound stimuli (signals) signaled the trial outcome. We assessed control by signal dimensions in Conflicting trials, in which the dimensions signaled conflicting outcomes. Unlike our previous experiment, signals remained present during terminal links. During initial links, preference favored the signaled key in Signaled trials, and the key signaled by the dimension exerting stronger control in Conflicting trials, suggesting strong signal control. Initial-link choice also depended on trial outcomes; preference was overall biased towards the smaller-sooner key. Terminal-link responding was primarily controlled by the key peck producing terminal-link entry, although some weak signal control was also evident. Thus, signal control during initial and terminal links was enhanced, and control by key-peck location during terminal links persisted, when signals remained present during terminal links. This suggests that our previous findings were partly related to temporal separation between signals and trial outcomes, and to history effects producing strong control by key-peck location.

Outcomes and anticoagulation use for elderly patients that present with an acute hip fracture: multi-centre, retrospective analysis.

BACKGROUND: Hip fractures are a common problem and corrective surgery is recommended within 24 h. However, most peri-operative direct oral anticoagulant (DOAC) guidelines suggest a washout period of 48 h before major surgery. There are limited data on utility of drug levels. AIM: To investigate the effect of DOAC therapy on time to surgery and patient outcomes, and to explore the impact of different pre-operative protocols on surgical delay. METHODS: A multi-centre, retrospective analysis of all adult patients that presented with acute hip fracture at three tertiary hospitals in Perth, Western Australia, was performed. Data were collated from the West Australian hip fracture registry and electronic records. Time to theatre, DOAC levels, bleeding and transfusion rates were compared between sites. RESULTS: Of 1240 hip fracture patients, 146 (11.9%) were on anticoagulation, with more patients taking a DOAC than warfarin. The time to surgery was significantly longer for those on a DOAC compared with those on warfarin (P = 0.003). There was no difference in bleeding, transfusion requirement or 30-day mortality in patients taking a DOAC compared to those on warfarin. Fifty-eight (70.7%) patients had a DOAC level prior to surgery. Of 25 patients who had a level performed within 12 h of presentation, 13 (52%) had a result of ≤50 ng/mL. Outcomes were similar between sites. CONCLUSION: People on DOAC treatment had a significant delay before corrective surgery compared with those on warfarin. The frequent finding of early DOAC levels <50 ng/mL suggests this delay may be unnecessary in a significant proportion of patients.

Routine Esophagograms After Hiatus Hernia Repair Minimizes Reoperative Morbidity: A Multicenter Comparative Cohort Study.

OBJECTIVE: Determine the utility of routine esophagograms after hiatus hernia repair and its impact on patient outcomes. BACKGROUND: Hiatus hernia repairs are common. Early complications such asre-herniation, esophageal obstruction and perforation, although infrequent, incur significant morbidity. Whether routine postoperative esophagograms enable early recognition of these complications, expedite surgical management, reduce reoperative morbidity, and improve functional outcomes are unclear. METHODS: Analysis of a prospectively-maintained database of hiatus hernia repairs in 14 hospitals, and review of esophagograms in this cohort. Results: A total of 1829 hiatus hernias were repaired. Of these, 1571 (85.9%) patients underwent a postoperative esophagogram. Overall, 1 in 48 esophagograms resulted in an early (<14 days) reoperation, which was undertaken in 44 (2.4%) patients. Compared to those without an esophagogram, patients who received this test before reoperation (n = 37) had a shorter time to diagnosis (2.4 vs 3.9 days, P = 0.041) and treatment (2.4 vs 4.3 days, P = 0.037) of their complications. This was associated with lower rates of open surgery (10.8% vs 42.9%, P = 0.034), gastric resection (0.0% vs 28.6%, P = 0.022), postoperative morbidity (13.5% vs 85.7%, P < 0.001), unplanned intensive care admission (16.2% vs 85.7%, P < 0.001), and decreased length-of-stay (7.3 vs 18.3 days, P = 0.009). Furthermore, we identified less intraoperative and postoperative complications, and superior functional outcomes at 1-year follow-up in patients who underwent early reoperations for an esophagogram-detected asymptomatic re-herniation than those who needed surgery for late symptomatic recurrences. CONCLUSIONS: Postoperative esophagograms decrease the morbidity associated with early and late reoperations, and should be considered for routine use after hiatus hernia surgery.

The Use of Induced Pluripotent Stem Cells to Study the Effects of Adenosine Deaminase Deficiency on Human Neutrophil Development.

Inherited defects that abrogate the function of the adenosine deaminase (ADA) enzyme and consequently lead to the accumulation of toxic purine metabolites cause profound lymphopenia and severe combined immune deficiency. Additionally, neutropenia and impaired neutrophil function have been reported among ADA-deficient patients. However, due to the rarity of the disorder, the neutrophil developmental abnormalities and the mechanisms contributing to them have not been characterized. Induced pluripotent stem cells (iPSC) generated from two unrelated ADA-deficient patients and from healthy controls were differentiated through embryoid bodies into neutrophils. ADA deficiency led to a significant reduction in the number of all early multipotent hematopoietic progenitors. At later stages of differentiation, ADA deficiency impeded the formation of granulocyte colonies in methylcellulose cultures, leading to a significant decrease in the number of neutrophils generated from ADA-deficient iPSCs. The viability and apoptosis of ADA-deficient neutrophils isolated from methylcellulose cultures were unaffected, suggesting that the abnormal purine homeostasis in this condition interferes with differentiation or proliferation. Additionally, there was a significant increase in the percentage of hyperlobular ADA-deficient neutrophils, and these neutrophils demonstrated significantly reduced ability to phagocytize fluorescent microspheres. Supplementing iPSCs and methylcellulose cultures with exogenous ADA, which can correct adenosine metabolism, reversed all abnormalities, cementing the critical role of ADA in neutrophil development. Moreover, chemical inhibition of the ribonucleotide reductase (RNR) enzyme, using hydroxyurea or a combination of nicotinamide and trichostatin A in iPSCs from healthy controls, led to abnormal neutrophil differentiation similar to that observed in ADA deficiency, implicating RNR inhibition as a potential mechanism for the neutrophil abnormalities. In conclusion, the findings presented here demonstrate the important role of ADA in the development and function of neutrophils while clarifying the mechanisms responsible for the neutrophil abnormalities in ADA-deficient patients.