Vascular Function, Systemic Inflammation, and Coagulation Activation 18 Months after COVID-19 Infection: An Observational Cohort Study.

INTRODUCTION: Among its effect on virtually all other organs, COVID-19 affects the cardiovascular system, potentially jeopardizing the cardiovascular health of millions. Previous research has shown no indication of macrovascular dysfunction as reflected by carotid artery reactivity, but has shown sustained microvascular dysfunction, systemic inflammation, and coagulation activation at 3 months after acute COVID-19. The long-term effects of COVID-19 on vascular function remain unknown. MATERIALS AND METHODS: This cohort study involved 167 patients who participated in the COVAS trial. At 3 months and 18 months after acute COVID-19, macrovascular dysfunction was evaluated by measuring the carotid artery diameter in response to cold pressor testing. Additionally, plasma endothelin-1, von Willebrand factor, Interleukin(IL)-1ra, IL-6, IL-18, and coagulation factor complexes were measured using ELISA techniques. RESULTS: The prevalence of macrovascular dysfunction did not differ between 3 months (14.5%) and 18 months (11.7%) after COVID-19 infection (p = 0.585). However, there was a significant decrease in absolute carotid artery diameter change, 3.5% ± 4.7 vs. 2.7% ± 2.5, p-0.001, respectively. Additionally, levels of vWF:Ag were persistently high in 80% of COVID-19 survivors, reflecting endothelial cell damage and possibly attenuated endothelial function. Furthermore, while levels of the inflammatory cytokines interleukin(IL)-1RA and IL-18 were normalized and evidence of contact pathway activation was no longer present, the concentrations of IL-6 and thrombin:antithrombin complexes were further increased at 18 months versus 3 months (2.5 pg/mL ± 2.6 vs. 4.0 pg/mL ± 4.6, p = 0.006 and 4.9 µg/L ± 4.4 vs. 18.2 µg/L ± 11.4, p < 0.001, respectively). DISCUSSION: This study shows that 18 months after COVID-19 infection, the incidence of macrovascular dysfunction as defined by a constrictive response during carotid artery reactivity testing is not increased. Nonetheless, plasma biomarkers indicate sustained endothelial cell activation (vWF), systemic inflammation (IL-6), and extrinsic/common pathway coagulation activation (FVII:AT, TAT) 18 months after COVID-19 infection.

Investigation of Physical Phenomena Underlying Temporal-Enhanced Ultrasound as a New Diagnostic Imaging Technique: Theory and Simulations.

Temporal-enhanced ultrasound (TeUS) is a novel noninvasive imaging paradigm that captures information from a temporal sequence of backscattered US radio frequency data obtained from a fixed tissue location. This technology has been shown to be effective for classification of various in vivo and ex vivo tissue types including prostate cancer from benign tissue. Our previous studies have indicated two primary phenomena that influence TeUS: 1) changes in tissue temperature due to acoustic absorption and 2) micro vibrations of tissue due to physiological vibration. In this paper, first, a theoretical formulation for TeUS is presented. Next, a series of simulations are carried out to investigate micro vibration as a source of tissue characterizing information in TeUS. The simulations include finite element modeling of micro vibration in synthetic phantoms, followed by US image generation during TeUS imaging. The simulations are performed on two media, a sparse array of scatterers and a medium with pathology mimicking scatterers that match nuclei distribution extracted from a prostate digital pathology data set. Statistical analysis of the simulated TeUS data shows its ability to accurately classify tissue types. Our experiments suggest that TeUS can capture the microstructural differences, including scatterer density, in tissues as they react to micro vibrations.

Altered Cell-Cycle Control, Inflammation, and Adhesion in High-Risk Persistent Bronchial Dysplasia.

Persistent bronchial dysplasia is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. In this study, we hypothesized that differences in gene expression profiles between persistent and regressive bronchial dysplasia would identify cellular processes that underlie progression to SCC. RNA expression arrays comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes [ANOVA, FDR ≤ 0.05). Thirty-one pathways showed significantly altered activity between the two groups, many of which were associated with cell-cycle control and proliferation, inflammation, or epithelial differentiation/cell-cell adhesion. Cultured persistent bronchial dysplasia cells exhibited increased expression of Polo-like kinase 1 (PLK1), which was associated with multiple cell-cycle pathways. Treatment with PLK1 inhibitor induced apoptosis and G2-M arrest and decreased proliferation compared with untreated cells; these effects were not seen in normal or regressive bronchial dysplasia cultures. Inflammatory pathway activity was decreased in persistent bronchial dysplasia, and the presence of an inflammatory infiltrate was more common in regressive bronchial dysplasia. Regressive bronchial dysplasia was also associated with trends toward overall increases in macrophages and T lymphocytes and altered polarization of these inflammatory cell subsets. Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of bronchial dysplasia. These results identify alterations in the persistent subset of bronchial dysplasia that are associated with high risk for progression to invasive SCC. These alterations may serve as strong markers of risk and as effective targets for lung cancer prevention.Significance: Gene expression profiling of high-risk persistent bronchial dysplasia reveals changes in cell-cycle control, inflammatory activity, and epithelial differentiation/cell-cell adhesion that may underlie progression to invasive SCC. Cancer Res; 78(17); 4971-83. ©2018 AACR.

Detection and grading of prostate cancer using temporal enhanced ultrasound: combining deep neural networks and tissue mimicking simulations.

PURPOSE  : Temporal Enhanced Ultrasound (TeUS) has been proposed as a new paradigm for tissue characterization based on a sequence of ultrasound radio frequency (RF) data. We previously used TeUS to successfully address the problem of prostate cancer detection in the fusion biopsies. METHODS  : In this paper, we use TeUS to address the problem of grading prostate cancer in a clinical study of 197 biopsy cores from 132 patients. Our method involves capturing high-level latent features of TeUS with a deep learning approach followed by distribution learning to cluster aggressive cancer in a biopsy core. In this hypothesis-generating study, we utilize deep learning based feature visualization as a means to obtain insight into the physical phenomenon governing the interaction of temporal ultrasound with tissue. RESULTS  : Based on the evidence derived from our feature visualization, and the structure of tissue from digital pathology, we build a simulation framework for studying the physical phenomenon underlying TeUS-based tissue characterization. CONCLUSION  : Results from simulation and feature visualization corroborated with the hypothesis that micro-vibrations of tissue microstructure, captured by low-frequency spectral features of TeUS, can be used for detection of prostate cancer.

Impaired gastrointestinal mucosal defense in Hirschsprung's disease: a clue to the pathogenesis of enterocolitis?

Twelve patients with Hirschsprung's disease were studied to investigate why some children develop enterocolitis. Previous studies have failed to explain this adequately; they have also failed to explain why enterocolitis can occur many years after definitive surgery. Six of the 12 patients had enterocolitis. By assessing immunological mucosal defense, it was shown that these patients had a marked deficiency in transfer of secretory IgA across the gastrointestinal mucosal cell, and thus were prone to mucosal invasion of both pathogenic and commensal organisms. The abnormalities were detected upon initial investigation (at presentation) prior to the onset of enterocolitis, and persisted into later life. The significance of these findings with reference to predicting which children are prone to develop enterocolitis and their long-term susceptibility to recurrence are discussed.

The laparoscope and the undescended testis.

An empty scrotum with an impalpable testis/testes presents a difficult diagnostic and therapeutic problem. Many methods have been used in an attempt at, or as an aid to, the localization of these gonads including venography, ultrasonography, hormone manipulation, and surgical exploration. Laparoscopy has been recommended as an aid to diagnosis. We reviewed our experience with the laparoscope in the diagnosis and management of this problem over a 7-year period. Laparoscopy permitted planning of the approach to orchidopexy, depending on whether the vessels entered the deep inguinal ring. In the latter group 48% of the testes were found to be atrophic. We also found the laparoscope to be of value in performing the first stage of the Fowler-Stephens long loop vas orchidopexy in three cases, with long-term viability of the testes in two of these.

Transitional cell papillary bladder neoplasm in a girl: an unusual presentation.

An 8-year-old girl presented with the clinical features of acute appendicitis. The removed appendix was normal but the abdominal pain persisted. There were no urinary symptoms and bacteriological examination of the urine was negative. An ultrasound scan showed an intravesical tumor that was subsequently excised. Histology showed a grade 1 transitional cell papillary bladder carcinoma of low grade malignancy. All previously reported cases have presented with urinary tract symptoms, usually hematuria.

Troubles with the foreskin: one hundred consecutive referrals to paediatric surgeons.

To assess the reasons for and outcomes of referrals concerning the foreskin, 100 consecutive patients seen in paediatric clinics were followed to discharge. 18 referrals were for circumcision on religious grounds. Of the other 82, the main reason for referral was non-retractability or phimosis. At clinic, 24 (29%) of these were deemed normal for age, 31 (38%) were treated with topical steroid (successfully in 25), 9 (11%) were listed for preputioplasty, 7 (9%) were listed for adhesiolysis, 7 (9%) were listed for circumcision, and 4 were listed for other forms of surgery. 6 patients were identified as having balanitis xerotica obliterans (BXO), a condition that had not been suggested on referral. With the advent of new treatments for foreskin disorders, circumcision is decreasingly necessary. Knowledge of the natural history of the foreskin, and the use of topical steroids, could shift the management of paediatric foreskin problems from the hospital outpatient department to primary care. BXO is not sufficiently recognized as a form of phimosis that requires operation.

Early appendicitis--a safe diagnosis?

INTRODUCTION: Serosal inflammation of the appendix in association with a significant peritoneal exudate can be mistaken for early acute appendicitis. We highlight the importance of looking for other sources of intra-abdominal sepsis in this clinical setting. CLINICAL PICTURE: We present 3 cases of so-called "mild" appendicitis with serosal inflammation that was ultimately shown to be caused by Meckel's diverticulitis. TREATMENT: All 3 patients initially underwent an appendicectomy. In 2 of these cases, a further laparotomy and excision of a Meckel's diverticulum was carried out. All 3 made an uneventful recovery. CONCLUSION: Meckel's diverticulitis can mimic acute appendicitis in clinical history, physical findings and operative findings. It is important to always consider this as a possible cause for an acute abdomen.

Thoraco-abdominal birth injury--presentation, diagnosis and management in an unusual case.

As a result of a traumatic delivery a newborn male child developed thoracic and intra-abdominal problems. Haemoperitoneum and chylous ascites were diagnosed; from a scrotal enlargement secondary to bilateral patent processus vaginalis and a chylothorax became apparent during investigation of the scrotal swellings. We discuss the presentation, diagnosis and management of the case and review the literature.

An unusual 'appendix' testis.

A six-week-old infant was seen with bilateral inguinal herniae. It was noted that the position of the right testis within the scrotum varied with the degree of inguinal herniation. At exploration the appendix was found lying within the patent processus vaginalis with its tip firmly adherent to the upper pole of the right testis. Appendicectomy was performed through the same incision. This unusual finding should be considered by the clinician if presented with a child with easily reducible inguinal herniae and a fluctuating testicular position.

Urethral valves--treatment, results and urodynamic assessment.

Posterior urethral valves is an uncommon condition, but it poses many diagnostic and therapeutic problems. Long term follow up of these patients revealed that the majority of these boys have long term problems. In depth assessment of 10 boys with this problem revealed that their upper urinary tracts remained stable whereas urodynamic studies showed gross micturition abnormalities. Most methods of assessing the urinary tracts in these boys are invasive (eg. Intravenous urography, micturating cystography) and may indeed show no change in upper tract radiology despite marked abnormalities of micturition detected by urodynamics and which may require further investigation and treatment. We therefore recommend regular urodynamic assessment of these boys as it is accurate and initially non-invasive. Those boys with a detectable abnormality can progress to further studies.

Surgical treatment of ingrown toenails in children: what is best practice?

INTRODUCTION: Surgery for ingrowing toenails carries a significant re-operation rate. We reviewed our departmental figures to assess the optimal management of these patients. PATIENTS AND METHODS: We performed a 10-year retrospective review of all patients undergoing surgery for ingrown toenails (IGTN) in order to determine the operations most commonly used and the re-operation rate of each of these procedures. RESULTS: A total of 880 procedures were performed on 414 patients. The median age at operation was 8.5 years. About half (48%) of children underwent two or more procedures with wedge excision and phenol application being the most common initial and repeat procedure. Recurrent surgery was most likely following plain avulsion or wedge avulsion without phenol application. Excision of the nailbed with phenol application had the lowest recurrence rate at 18.4%. CONCLUSIONS: We recommend wedge resection with phenol application as first-line treatment with simple avulsion reserved for severely infected toes. Total nail bed excisions should be reserved for patients with significant on-going morbidity associated with IGTN. Families must be made aware of the likely outcome of IGTN surgery and the choice of operation must be tailored to the individual.

Scrotal swellings in the under 5s.

Scrotal swelling is a common cause of referral to the paediatric surgical services in Edinburgh, constituting 12% of total admissions. Of these, 2818 (65%) were in boys under the age of 5 years, with a wide variety, including inguinal hernias, hydroceles, testicular torsion, tumours, and some interesting but uncommon conditions. A retrospective study was performed over a 12 year period to assess the incidence, aetiology, mode of presentation, disease, and management of scrotal swellings in boys under 5. Although most of the causes of these swellings were easily elucidated from a history and clinical examination, it was apparent that a high level of suspicion was also necessary to ensure that more serious problems did not go undetected.

Just a 'wee prick' with a needle.

Difficulty with vascular access is a common problem in neonatal medicine and surgery. Recent advances in parenteral therapy/nutrition and manufacture of high quality intravenous lines have enabled smaller infants to survive. Thus, in the small surgical neonate, the insertion of an indwelling intravenous long line (either percutaneously or at cut down) is a frequent occurrence. This procedure is not without its complications and it is thus necessary for the clinician inserting these lines to be aware of this and fully understand the regional anatomy of the area being used. I wish to report an unusual complication which posed several diagnostic and management problems.

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).

A child of 11 years with a solitary involvement of the right radius by sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is presented. The literature of bone involvement in this condition is reviewed.

Microbiological studies of the enterocolitis of Hirschsprung's disease.

The results of a prospective study of 20 cases of newly diagnosed Hirschsprung's disease (nine of whom developed enterocolitis) and 10 normal controls showed no variations in the bacterial flora (including Clostridium difficile) in the stools of the groups studied. Viral studies showed that rotavirus was present in the stools of seven of the nine cases of enterocolitis during the episode. We suggest that Hirschsprung's enterocolitis may have a complex infective aetiology and that rotavirus plays a part.

Ante-natal testicular torsion: only one cause of the testicular regression syndrome?

It has been suggested that the most likely cause of the Testicular Regression Syndrome (TRS) is ante-natal torsion of the testis. As testicular torsion is twice as common on the left this theory cannot explain the incidence of right sided or bilateral cases. From a 5-year retrospective surgical and pathological review, we confirmed that the left testis was the most commonly affected, that boys with TRS tended to be delivered closer to term, and that frequently both testes were present at birth, but one or both subsequently vanished. We also found that direct trauma can produce histological findings indistinguishable from TRS. Close to term, fetal testes are liable to be intrascrotal and therefore susceptible to direct trauma. As the left testis descends into the scrotum at an earlier stage than the right, it is therefore at greater risk of injury. Since the findings of TRS can be produced by direct trauma, we suggest that intra-partum trauma may predispose to the TRS.