Incidence of medullary thyroid carcinoma and Hirschsprung disease based on the cosmos database.

PURPOSE: Multiple endocrine neoplasia Type 2A (MEN2A) can occur with Hirschsprung disease (HD) due to mutation in the RET proto-oncogene, with the majority developing medullary thyroid carcinoma (MTC). Given the comorbidity, many parents have contacted us to share concerns and unfortunate experiences about the prevalence rates of MEN2A/MTC in patients with HD. The aim is to determine the prevalence rate of patients with HD and MEN2A or medullary thyroid carcinoma, respectively. METHODS: This is a cross-sectional study of the COSMOS database from January 01, 2017, to March 08, 2023. The database was searched for patients diagnosed with MEN2A, MTC, and HD. IRB exemption was provided (COMIRB #23-0526). RESULTS: The database contained 183,993,122 patients from 198 contributing organizations. The prevalence of HD and MEN2A was 0.00002%, and for HD and MTC was 0.000009%. One in 66 patients (1.5%) with MEN2A also had HD. One in 319 patients (0.3%) in the HD group had MEN2A. One in 839 patients (0.1%) within the HD population had MTC. CONCLUSION: The prevalence of MTC and HD or MEN2A and HD in the study population was low. Considering that almost all MEN2A patients have a positive family history, this data does not support the general genetic testing of HD patients.

Standardization of radiograph readings during bowel management week.

INTRODUCTION: During "bowel management week," abdominal radiographs are used to monitor the amount and location of stool. A radiologist familiar with the treatment plan can provide an improved interpretation. The goal of this paper is to standardize the radiological reports during a bowel management week. METHODS: We saw 744 patients during bowel management week from May 2016 until March 2023. Diagnosis included: anorectal malformation (397), idiopathic constipation (180), Hirschsprung disease (89), and spina bifida (78). Laxatives were the treatment for 51% of patients, and 49% received enemas. Characteristic radiographs were selected for each treatment group for a proposed reading standardization. RESULTS: When the stool is visualized, it is crucial to report its location. Having a contrast enema helps with the correct interpretation of the colonic anatomy. It is also essential to always compare the amount of stool with the radiograph from the previous day to determine if there is an increase or decrease in stool. Examples of radiographs are shown to guide the use of the preferred proposed terminology. CONCLUSION: Providing information regarding which treatment modality the patient is receiving and stating that a patient is on a bowel management week treatment is crucial for the radiologist to provide adequate interpretation. The radiologist must be familiar with the treatment goals and purpose of the daily radiograph.

Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in "22-23" week and "24-26" infants.

The hemodynamically significant patent ductus arteriosus (hsPDA) is a controversial topic in neonatology, particularly among neonates at the earliest gestational ages of 22+0-23+6 weeks. There is little, to no data on the natural history or impact of the PDA in extremely preterm babies. In addition, these high-risk patients have typically been excluded from randomized clinical trials of PDA treatment. In this work, we present the impact of early hemodynamic screening (HS) of a cohort of patients born 22+0-23+6 weeks gestation who either were diagnosed with hsPDA or died in the first postnatal week as compared to a historical control (HC) cohort. We also report a comparator population of 24+0-26+6 weeks gestation. All patients in the HS epoch were evaluated between 12-18h postnatal age and treated based on disease physiology whereas the HC patients underwent echocardiography at the discretion of the clinical team. We demonstrate a two-fold reduction in the composite primary outcome of death prior to 36 weeks or severe BPD and report a lower incidence of severe intraventricular hemorrhage (n=5, 7% vs n=27, 27%), necrotizing enterocolitis (n=1, 1% vs n=11, 11%) and first-week vasopressor use (n=7, 11% vs n=40, 39%) in the HS cohort. HS was also associated with an increase in survival free of severe morbidity from the already high rate of 50% to 73% among neonates <24 weeks gestation. We present a biophysiological rationale behind the potential modulator role of hsPDA on these outcomes and review the physiology relevant to neonates born at these extremely preterm gestations. These data highlight the need for further interrogation of the biological impact of hsPDA and impact of early echocardiography directed therapy in infants born less than 24 weeks gestation.

Do adult patients with congenital colorectal conditions know their diagnosis?

PURPOSE: Limited research exists about the knowledge that adult patients have about their congenital colorectal diagnosis. METHODS: This was an IRB approved, prospective study of patients in the Adult Colorectal Research Registry who completed surveys between October 2019 and March 2022. Surveys were administered through REDCap after patients consented to being contacted for research purposes. Patients provided demographic data, which was linked to surgical records, and the diagnoses provided by patients were compared with diagnoses recorded by the original surgeons. RESULTS: One hundred and thirty-one questionnaires were collected, 115 patients had anorectal malformations (ARM) and 16 had Hirschsprung disease (HD). Seven patients who had ARM were unaware that they had an ARM or HD. The type of ARM recorded by the surgeon was unavailable for comparison with the patient's reported diagnosis in four cases. Of the 111 remaining patients with ARM, only 32 of them (29%) knew what their own type of anomaly was. Female patients recalled their diagnosis more often than male patients (42.4% vs 13.5%). All 16 participants with HD correctly identified their diagnosis severity as HD with or without total colonic aganglionosis. CONCLUSION: The results of this study demonstrate patient's limited understanding of their type of ARM and highlight the urgent need to enhance communication and education strategies, such as issuing patients with medical diagnosis identification cards. It is critical for clinicians to better communicate with patients to ensure that they and their relatives truly understand their precise diagnosis. Adequately informed patients can better advocate for themselves, adhere to treatments and precautionary recommendations and navigate the complexities of transitional care. Consequently they can more effectively manage their lifelong complications.

[Cystic fibrosis and computed tomography of the lungs]. / Computertomographie der Lunge bei Mukoviszidose.

With its high detail of morphological changes in lung parenchyma and airways as well as the possibilities for three-dimensional reconstruction, computed tomography (CT) represents a solid tool for the diagnosis and follow-up in patients suffering from cystic fibrosis (CF). Guidelines for standardized CT image acquisition in CF patients are still missing. In the mostly younger CF patients, an important issue is the well-considered use of radiation in CT imaging. The use of intravenous contrast agent is mainly restricted to acute emergency diagnostics. Typical morphological findings in CF lung disease are bronchiectasis, mucus plugging, or signs of decreased ventilation (air trapping) which can be detected with CT even in early stages. Various scoring systems that have become established over time are used to grade disease severity and for structured follow-up, e.g., in clinical research studies. With the technical development of CT, a number of postprocessing software tools were developed to help clinical reporting and overcome interreader differences for a standardized quantification. As an imaging modality free of ionizing radiation, magnetic resonance imaging (MRI) is becoming increasingly important in the diagnosis and follow-up of CF patients and is already frequently a substitute for CT for long-term follow-up at numerous specialized centers.

Tethered cord in children with anorectal malformations with emphasis on rectobladder neck fistula.

PURPOSE: To find the incidence of tethered cord (TC) in patients with anorectal malformations (ARM) and to determine the relationship between bowel/urinary control and TC in a subset of patients with rectobladder neck fistula (RBNF). METHODS: The database of a tertiary medical center was retrospectively collected for all patients treated for ARM from 1980 to 2012. All patients with TC and RBNF were identified. RESULTS: Among 790 patients, who underwent screening for TC, 285(36%) were diagnosed with TC. Eleven of 37 screened patients with RBNF were diagnosed with TC. The median follow-up period was 49 months (range 2-222 months). TC was diagnosed in 3/18(16.6%) patients with sacral ratio (SR) ≥ 0.7; 4/12(33.3%) with SR 0.41-0.69; and 4/7(57.1%) patients with SR 0-0.4. The association of TC in RBNF patients had a negative influence in the prognosis for bowel and urinary control. CONCLUSION: The incidence of TC among patients with ARM is 36%. Incidence of TC among patients with RBNF correlates with SR value and is higher with lower SR. Patients with RBNF and TC have dismal prognosis for bowel control, unrelated to their SR status. Many unresolved questions related to the management of ARM patients with asymptomatic TC still remain.

The fetal programming of food preferences: current clinical and experimental evidence.

Increased energy consumption is one of the major factors implicated in the epidemic of obesity. There is compelling evidence, both clinical and experimental, that fetal paucity of nutrients may have programming effects on feeding preferences and behaviors that can contribute to the development of diseases. Clinical studies in different age groups show that individuals born small for their gestational age (SGA) have preferences towards highly caloric foods such as carbohydrates and fats. Some studies have also shown altered eating behaviors in SGA children. Despite an apparent discrepancy in different age groups, all studies seem to converge to an increased intake of palatable foods in SGA individuals. Small nutrient imbalances across lifespan increase the risk of noncommunicable diseases in adult life. Homeostatic factors such as altered responses to leptin and insulin and alterations in neuropeptides associated with appetite and satiety are likely involved. Imbalances between homeostatic and hedonic signaling are another proposed mechanism, with the mesocorticolimbic dopaminergic pathway having differential reward and pleasure responses when facing palatable foods. Early exposure to undernutrition also programs hypothalamic-pituitary-adrenal axis, with SGA having higher levels of cortisol in different ages, leading to chronic hyperactivity of this neuroendocrine axis. This review summarizes the clinical and experimental evidence related to fetal programming of feeding preferences by SGA.

The Gonzalez hernia revisited: use of the ischiorectal fat pad to aid in the repair of rectovaginal and rectourethral fistulae.

INTRODUCTION: During the development of the posterior sagittal approach to anorectal malformations a vital technical challenge was a precise midline dissection, which if off, allowed for the ischiorectal fat pad to bulge into the wound. This occurrence became affectionately known as a "Gonzalez hernia", after a trainee of Dr Pena's (and a co-author of this paper). We describe here an innovative use of the ischiorectal fat pad to aid in the repair of acquired rectovaginal and rectourethral fistulae. METHODS: Patients with recurrent vaginal or urethral fistulae were selected for review. The ischiorectal fat pad was deliberately mobilized (via a posterior sagittal or transanal approach) and used to buttress the repair of the posterior vagina or urethra. RESULTS: The ischiorectal fat pad technique was used in 9 patients. All had an acquired fistula (6 rectovaginal fistula, 3 rectourethral fistulas). We used the posterior sagittal approach in 7 and in 2 the transanal approach. Six patients had had at least two prior attempts at fistula repair. Six patients had a stoma, and 3 did not. There were no recurrences in greater than six month follow-up. DISCUSSION: The ischiorectal fat pad is easily visualized and mobilized, either via a posterior sagittal or transanal approach, providing excellent coverage with native, well-vascularized tissue, in an area that is difficult to heal. It is an excellent option for recurrent rectovaginal and rectovaginal fistulae and may have other additional creative applications.

Antibiotic use during pregnancy alters the commensal vaginal microbiota.

Antibiotics may induce alterations in the commensal microbiota of the birth canal in pregnant women. Therefore, we studied the effect of antibiotic administration during pregnancy on commensal vaginal bacterial colonization at gestational week 36. Six hundred and sixty-eight pregnant women from the novel unselected Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010 ) pregnancy cohort participated in this analysis. Detailed information on oral antibiotic prescriptions during pregnancy filled at the pharmacy was obtained and verified prospectively. Vaginal samples were obtained at pregnancy week 36 and cultured for bacteria. Women who received oral antibiotics during any pregnancy trimester had an increased rate of colonization by Staphylococcus species in the vaginal samples as compared with samples obtained from women without any antibiotic treatment during pregnancy (adjusted OR 1.63, 95% CI 1.06-2.52, p 0.028). Oral antibiotic administration in the third trimester were also associated with increased colonization by Staphylococcus species (adjusted OR 1.98, 95% CI 1.04-3.76, p 0.037). These bacteriological changes were associated with urinary tract infection antibiotics. Women treated in the third trimester of pregnancy were more often colonized by Escherichia coli than women without antibiotic treatment in the third trimester (adjusted OR 1.91, 95% CI 1.04-3.52, p 0.038). This change was associated with respiratory tract infection (RTI) antibiotics. We did not observe any significant changes in vaginal Streptococcus agalactiae (group B streptoccocus) or Staphylococcus aureus colonization following antibiotic treatment in pregnancy. Antibiotic administration during pregnancy leads to alterations in the vaginal microbiological ecology prior to birth, with potential morbidity, and long-term effects on the early microbial colonization of the neonate.

Deep phenotyping of the unselected COPSAC2010 birth cohort study.

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.

The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens junctions integrity.

Epithelial cell-cell contacts are mediated by E-cadherin interactions, which are regulated by the balanced local activity of Rho GTPases. Despite the known function of Rho at adherens junctions (AJs), little is known about the spatial control of Rho activity at these sites. Here we provide evidence that in breast epithelial cells the Deleted in Liver Cancer 3 (DLC3) protein localizes to AJs and is essential for E-cadherin function. DLC3 is a still poorly characterized RhoA-specific GTPase-activating protein that is frequently downregulated in various types of cancer. We demonstrate that DLC3 depletion leads to mislocalization of E-cadherin and catenins, which was associated with impaired cell aggregation and increased migration. This is explained by aberrant local Rho signaling because ROCK inhibition restored cell-cell contacts in DLC3 knockdown cells. We thus identify DLC3 as a novel negative regulator of junctional Rho and propose that DLC3 loss contributes to carcinogenesis by compromising epithelial integrity.

[Serotonin receptor 1A-modulated dephosphorylation of glycine receptor α3: a new molecular mechanism of breathing control for compensation of opioid-induced respiratory depression without loss of analgesia]. / Die von Serotoninrezeptor 1A modulierte Dephosphorylierung des Glyzinrezeptors α3: Ein neuer molekularer Mechanismus der Atmungskontrolle zur Kompensation opioidinduzierter Atemdepression ohne Verlust der Analgesie.

To control the breathing rhythm the medullary respiratory network generates periodic salvo activities for inspiration, post-inspiration and expiration. These are under permanent modulatory control by serotonergic neurons of the raphe which governs the degree of phosphorylation of the inhibitory glycine receptor α3. The specific activation of serotonin receptor type 1A (5-HTR(1A)), which is strongly expressed in the respiratory neurons, functions via inhibition of adenylate cyclase and the resulting reduction of the intracellular cAMP level and a gradual dephosphorylation of the glycine receptor type α3 (GlyRα3). This 5-HTR(1A)-GlyRα3 signal pathway is independent of the µ-opioidergic transduction pathway and via a synaptic inhibition caused by an increase in GlyRα3 stimulates a disinhibition of some target neurons not only from excitatory but also from inhibitory neurons. Our physiological investigations show that this 5-HTR(1A)-GlyRα3 modulation allows treatment of respiratory depression due to opioids without affecting the desired analgesic effects of opioids. The molecular mechanism presented here opens new pharmacological possibilities to treat opioid-induced respiratory depression and respiratory disorders due to disturbed inhibitory synaptic transmission, such as hyperekplexia.

Which techniques are relevant in the surgical management of the nasal tip?

In this article, we give an overview of safe and consistent techniques for nasal tip surgery. A change in the morphology of the tip has an impact on the profile of the face. A knowledge of facial proportions is therefore important when performing rhinoplastic surgery. We prefer an external approach because it provides the best overview and because the possibility of bimanual working makes manipulation of the lower lateral cartilages easier. The techniques described here can be used to alter the nasal tip in a controllable way.

Knee arthroplasty for spontaneous osteonecrosis of the knee: unicompartimental vs bicompartimental knee arthroplasty.

Spontaneous osteonecrosis of the knee (SON) is an osteonecrosis that mainly affects the medial femoral condyle. In endstage SON, knee arthroplasty is the therapy of choice. Because of the unicompartimental nature of the knee, unicondylar knee arthroplasty is considered an ideal implant for treatment of this condition. The purpose of this study was to prove that the long-term results of unicondylar implants are better than the results of bicondylar implants for the treatment of SON. All patients treated for SON between 1984 and 2000 have been recorded. Two groups were formed according to the implant used. In all patients the preoperative radiograph was analyzed according to stage and size of the osteonecrotic lesion and the osteoarthritic changes. Postoperatively, the Knee Society Score and the radiograph were recorded. Thirty-nine patients were included in this study, of which 23 patients were treated by a unicondylar implant and 16 by a bicondylar implant. On a short-term basis, unicondylar implants had better clinical results; however, on a long-term basis bicondylar implants were better. In comparison, only unicondylar implants had to be revised. Radiolucency lines were mainly observed in patients with unicondylar impants and large areas of osteonecrosis. Our long-term results suggest that patients with SON are better treated by bicondylar implants. The reasons for the higher failure rate for unicondylar implants are poor bone stock and secondary arthritic changes.