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The airways are frequently involved in nonneoplastic lung diseases, and sometimes their involvement dominates the clinical picture. In these situations, the combination of clinical and radiologic findings is sometimes sufficient to reach a firm diagnosis; however, in a significant proportion of cases a biopsy is obtained, frequently representing a challenge for the practicing pathologists. In the present chapter, beside the description of some well defined entities, we present the most relevant morphologic features that can be encountered on small endoscopic biopsies and on surgical samples, trying to identify the elementary lesions and to correlate them with the complexity of the different clinical settings where they can be found. It is a rare case in which the morphological features are diagnostic per se of a specific disease. Conversely, the identification of a few key elementary lesions can be of help to narrow the differential diagnoses that can be offered to clinicians to complete the difficult puzzle of interstitial lung diseases.

• The presentation of urinary tract infections (UTIs) in neonates differs from that seen in older children. • The type and route of infection also differ in neonates, when compared with older children. • An appropriate urine sample for diagnosis is needed, but treatment should not be delayed. • A neonate in whom a UTI is suspected should be evaluated for sepsis, including invasive cultures. • After a documented neonatal UTI, a radiologic work-up is warranted to detect anatomic anomalies. • Vesicoureteral reflux (VUR) is diagnosed in 30%–50% of neonates with proven UTI. • Voiding cystourethrogram is the gold standard for the diagnosis of VUR and should be performed on high-risk neonates. • Treatment of VUR should be tailored to each patient's individual risk of UTI recurrence, with the goals of preventing future UTIs and renal scar formation.

Routine blood culture is used for the detection of bloodstream infections by aerobic and anaerobic bacteria and by common pathogenic yeasts. A retrospective study was conducted in a public hospital in Maceió-AL, by collecting data of all medical records with positive blood cultures. Out of the 2,107 blood cultures performed, 17% were positive with Staphylococcus coagulase negative (51.14%), followed by Staphylococcus aureus (11.21%) and Klebsiella pneumoniae (6.32%). Gram-positive bacteria predominated among positive blood cultures, highlighting the group of Staphylococcus coagulase-negative. While Gram-negative bacteria had a higher number of species among positive blood cultures. Resumo A cultura sanguínea de rotina é usada para a detecção de infecções na corrente sanguínea por bactérias aeróbias e anaeróbias e por leveduras patogênicas comuns. Estudo retrospectivo realizado em hospital público de Maceió-AL, por meio da coleta de dados de todos os prontuários com culturas sanguíneas positivas. Das 2.107 culturas sanguíneas realizadas, 17% foram positivas com Staphylococcus coagulase negativo (51,14%), seguido por Staphylococcus aureus (11,21%) e Klebsiella pneumoniae (6,32%). As bactérias Gram-positiva predominaram entre as culturas de sangue positivas, destacando-se o grupo das Staphylococcus coagulase-negativo. Enquanto as bactérias Gram-negativas apresentaram um número maior de espécies entre as culturas de sangue positivas.

• Current American Urological Association guidelines do not recommend ultrasound for the evaluation of undescended testicles. • Children with an undescended testicle should be referred to a pediatric urologist at approximately 6 months of age. • Infants with bilateral nonpalpable testicles should be evaluated for possible congenital adrenal hyperplasia. • Infants with hypospadias and unilateral or bilateral undescended testicles should be evaluated for disorder of sexual development. • Repair of hypospadias is recommended at between 6 months and 1 year of age. • Bladder exstrophy repairs are currently delayed to 3 months of age. • A voiding cystourethrogram should be performed in infants with high-grade hydronephrosis and bilateral hydronephrosis. • Most hydroceles in infants are noncommunicating, and infants should be referred to a urologist if they fluctuate in size suggesting a communicating hydrocele. • Vesicoureteral reflux is more common in male infants and has a high rate of resolution.

Optimal specimen handling is essential for the accurate interpretation of biopsies and cytologic preparations obtained in the course of evaluating the patient with lung disease. Sampling techniques available include bronchoscopy, transthoracic needle core biopsy or aspiration, and surgical wedge biopsy of peripheral lung through a transthoracic approach. In this chapter specimen characteristics and processing steps are presented for each of the common lung samples taken in the course of clinical evaluation for pulmonary disease. Also, for each type of sample the benefits and limitations are reviewed. Such a working knowledge of specimen handling for each procedure ensures the greatest likelihood of success in establishing a specific diagnosis and, in the end, a rational treatment plan. The addition of clinical information dramatically increases the likelihood of a meaningful and accurate pathologic diagnosis, especially in the setting of biopsies for diffuse lung disease (interstitial lung disease).

Alzheimer’s disease (AD) is a neurodegenerative disorder known to affect functional connectivity (FC) across many brain regions. Linear FC measures have been applied to study the differences in AD by splitting neurophysiological signals, such as electroencephalography (EEG) recordings, into discrete frequency bands and analysing them in isolation from each other. We address this limitation by quantifying cross-frequency FC in addition to the traditional within-band approach. Cross-bispectrum, a higher-order spectral analysis approach, is used to measure the nonlinear FC and is compared with the cross-spectrum, which only measures the linear FC within bands. This work reports the reconstruction of a cross-frequency FC network where each frequency band is treated as a layer in a multilayer network with both inter- and intra-layer edges. Cross-bispectrum detects cross-frequency differences, mainly increased FC in AD cases inδ-θcoupling. Overall, increased strength of low-frequency coupling and decreased level of high-frequency coupling is observed in AD cases in comparison to healthy controls (HC). We demonstrate that a graph-theoretic analysis of cross-frequency brain networks is crucial to obtain a more detailed insight into their structure and function. Vulnerability analysis reveals that the integration and segregation properties of networks are enabled by different frequency couplings in AD networks compared to HCs. Finally, we use the reconstructed networks for classification. The extra cross-frequency coupling information can improve the classification performance significantly, suggesting an important role of cross-frequency FC. The results highlight the importance of studying nonlinearity and including cross-frequency FC in characterising AD.

Purpose To describe with multimodal imaging including the use of ultra-widefield optical coherence tomography (OCT) imaging a distinct phenotype of autosomal recessive nanophthalmos associated with a novel mutation of the MFRP gene (membrane-type frizzled-related protein). Methods Case report and review of the relevant literature. Patients Single patient followed by the Weill Cornell Medicine Department of Ophthalmology Retina and Glaucoma Services. Results A patient with a novel homozygous mutation in the MFRP gene (c.472C>T) presented with nanophthalmos, optic disc drusen, foveal hypoplasia, and extensive peripheral retinoschisis, which was revealed to be multilevel retinoschisis on ultra-wide field OCT. Unlike other reported cases, the findings associated with this novel mutation did not include foveoschisis nor clinically obvious retinitis pigmentosa. The patient underwent prophylactic peripheral laser iridotomy in both eyes. Conclusion Here we present a patient with nanophthalmos, optic disc drusen, and foveal hypoplasia associated with extensive peripheral retinoschisis imaged by ultra-widefield OCT, but not foveal retinoschisis or prominent retinitis pigmentosa. The findings may expand the clinical spectrum of MFRP-associated nanophthalmos.

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy.

Background Coma is one of the frequently encountered clinical conditions in any intensive care unit (ICU), which is responsible for considerable morbidity and mortality. Therefore, this study was designed to look at the clinical and EEG profile of Nonconvulsive Status Epilepticus (NCSE) in comatose ICU patients using portable electroencephalography (EEG). Methods In all 102 patients of unresponsive coma (GCS ≤ 8), who remained in poor sensorium despite 48 h of optimum treatment in ICU, were included in the study. All patients underwent 1 h of electroencephalography (EEG) monitoring with a portable EEG machine. All EEGs were screened according to Salzburg Consensus Criteria (SCC) for Nonconvulsive Status Epilepticus (NCSE). Patients with evidence of NCSE were administered parenteral Antiepileptic Drugs (AED). A repeat EEG was done after 24 h of baseline to ascertain the effect of AED. The primary outcome was the recognition of patients with NCSE on the basis of established EEG criteria. The secondary outcome measure was the Glasgow outcome scale (GOS) at the time of discharge. Results Out of 102 cases enrolled, 12 (11.8%) cases were detected to have NCSE on portable EEG. The mean age of patients with NCSE was 52.2 years. In terms of gender distribution, 2/12 (17%) were female, and 10/12 (83%) were male (M: F = 5:1). Median GCS was 6 (range 3–8). Looking at CNS infections, 4/12 (33.3%) had evidence of some form of CNS infection in the NCSE group, compared to 16/90 (18%) in the group without NCSE. This difference was statistically significant (P-value 2 points) after administration of AED’ was noted with good clinical outcomes (GOS 5). In five of these 12 cases, death was the final outcome (GOS 1). Conclusions NSCE should be considered in the differential diagnosis of all unresponsive comatose ICU patients. In resource-limited settings, where continuous EEG monitoring may not be feasible, bedside portable EEG testing can be used to diagnose patients with NCSE. Treating NCSE reverses epileptiform EEG changes and improves clinical outcomes in a subset of comatose ICU patients.

Introduction and Objectives Obstructive sleep apnea (OSA) is a prevalent sleep condition which is very heterogeneous although not formally characterized as such, resulting in missed or delayed diagnosis. Cluster analysis has been used in different clinical domains, particularly within sleep disorders. We aim to understand OSA heterogeneity and provide a variety of cluster visualizations to communicate the information clearly and efficiently. Materials and Methods We applied an extension of k-means to be used in categorical variables: k-modes, to identify OSA patients’ groups, based on demographic, physical examination, clinical history, and comorbidities characterization variables (n = 40) obtained from a derivation and validation cohorts (211 and 53, respectively) from the northern region of Portugal. Missing values were imputed with k-nearest neighbours (k-NN) and a chi-square test was held for feature selection. Results Thirteen variables were inserted in phenotypes, resulting in the following three clusters: Cluster 1, middle-aged males reporting witnessed apneas and high alcohol consumption before sleep; Cluster 2, middle-aged women with increased neck circumference (NC), non-repairing sleep and morning headaches; and Cluster 3, obese elderly males with increased NC, witnessed apneas and alcohol consumption. Patients from the validation cohort assigned to different clusters showed similar proportions when compared with the derivation cohort, for mild (C1: 56 vs 75%, P = 0.230; C2: 61 vs 75%, P = 0.128; C3: 45 vs 48%, P = 0.831), moderate (C1: 24 vs 25%; C2: 20 vs 25%; C3: 25 vs 19%) and severe (C1: 20 vs 0%; C2: 18 vs 0%; C3: 29 vs 33%) levels. Therefore, the allocation supported the validation of the obtained clusters. Conclusions Our findings suggest different OSA patients’ groups, creating the need to rethink these patients’ stereotypical baseline characteristics.

Purpose To describe central serous chorioretinopathy (CSCR) cases presenting as uveal effusion syndrome, providing new insights into "pachychoroid spectrum" diseases. Methods Clinical charts, color fundus photographs, fluorescein angiography, indocyanine green angiography, optical coherence tomography, ultrasound imaging, cerebral magnetic resonance imaging and biometry of four eyes of three patients were assessed. A literature review was conducted. Results The three patients had peripheral choroidal detachment and inferior bullous retinal detachment associated with CSCR features detected using multimodal imaging, including fluorescein and indocyanine green angiography. The choroid was thick in the three patients, and uveal effusion occurred after steroid treatment in all cases. Subretinal fluid drainage and deep sclerectomy with flaps of 4x4 mm in both inferior quadrants were performed in 3 eyes of 2 patients with good outcomes. One patient was treated with photodynamic therapy. All three patients developed a typical leopard-spot pigmentary pattern in the fundus. Conclusion A severe presentation of highly exudative CSCR may occur in rare cases with a peripheral choroidal detachment mimicking uveal effusion syndrome. These severe cases highlighted the role of choroidal thickening and hyperpermeability, choroidal vein dilation and possible scleral thickening in both entities.

Uterine contractions during labor and engagement of the fetus in the birth canal can compress the fetal head. Its impact on the fetus is unclear and still controversial. In this integrative physiological review, we highlight evidence that decelerations are uncommonly associated with fetal head compression. Next, the fetus has an impressive ability to adapt to increased intracranial pressure through activation of the intracranial baroreflex, such that fetal cerebral perfusion is well-maintained during labor, except in the setting of prolonged systemic hypoxemia leading to secondary cardiovascular compromise. Thus, when it occurs, fetal head compression is not necessarily benign but does not seem to be a common contributor to intrapartum decelerations. Finally, the intracranial baroreflex and the peripheral chemoreflex (the response to acute hypoxemia) have overlapping efferent effects. We propose the hypothesis that these reflexes may work synergistically to promote fetal adaptation to labor.

Malakoplakia is a rare granulomatous inflammatory disorder. Its diagnosis depends on histopathological findings; however, high-quality literature regarding proper medical/surgical treatment is lacking. A 38-year-old diabetic female patient was admitted to the emergency room with a history of lower gastrointestinal hemorrhage. Colonoscopy revealed a lesion in the descending colon, and abdominal computed tomography revealed a splenic flexure mass involving the lower pole of the spleen and upper pole of the left kidney. Biopsies confirmed the diagnosis of malakoplakia. After completing antibiotic treatment, a restaging computed tomography revealed a discrete mass increase; hence, the patient underwent laparoscopic en bloc colectomy and partial nephrectomy. Postoperatively, the patient developed a pancreatic fistula, which was successfully treated with percutaneous drainage and antibiotics. The presence of pathognomonic Michaelis-Gutmann inclusions on histopathology is frequently reported as the key to diagnosing malakoplakia. Herein, we present a successful, minimally invasive surgical treatment for colonic malakoplakia.

Purpose: Intestinal fibrosis is a common complication of inflammatory bowel diseases. However, the possible involvement of epithelial-mesenchymal transition (EMT) has been scarcely investigated. This systematic review aims to search through research papers that are focusing on messenger RNA (mRNA) and protein expression profile in EMT in fistula or in intestinal fibrosis.Methods: Electronic exploration was performed until April 24, 2019 through PubMed, Ovid, Science Direct, and Scopus databases with the terms of “fistula” OR “intestinal fibrosis” AND “epithelial-mesenchymal transition”. Two independent reviewers scrutinized the suitability of the title and abstract before examining the full text that met the inclusion criteria. For each study, the sample types that were used, methods for analysis, and genes expressed were identified. The list of genes was further analyzed using DAVID (Database for Annotation, Visualization, and Integrated Discovery) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway.Results: There were 896 citations found; however, only 3 studies fulfilled the requirements. Among the EMT-related genes, 5 were upregulated genes at mRNA level while 6 were at protein level. However, only 2 downregulated genes were found at each mRNA and protein level. Of the 4 inflammation-related genes found, 3 genes were upregulated at mRNA level and 1 at protein level. These genes were confirmed to be involved in the development of inflammatory induced fibrosis and fistula through EMT. Results from quantitative real-time polymerase chain reaction analysis were consistent with the process of EMT, confirmed by the western blot protein analysis.Conclusion: Many significant genes which are involved in the process of EMT in fistula and intestinal fibrosis have been identified. With high-end technology many more genes could be identified. These genes will be good molecular targets in the development of biomarkers for precision drug targeting in the future treatment of intestinal fibrosis and fistula.

The amplitude envelope of speech is crucial for accurate comprehension. Considered a key stage in speech processing, the phase of neural activity in the theta-delta bands (1-10 Hz) tracks the phase of the speech amplitude envelope during listening. However, the mechanisms underlying this envelope representation have been heavily debated. A dominant model posits that envelope tracking reflects entrainment of endogenous low-frequency oscillations to the speech envelope. Alternatively, envelope tracking reflects a series of evoked responses to acoustic landmarks within the envelope. It has proven challenging to distinguish these two mechanisms. To address this, we recorded MEG while participants (n= 12, 6 female) listened to natural speech, and compared the neural phase patterns to the predictions of two computational models: an oscillatory entrainment model and a model of evoked responses to peaks in the rate of envelope change. Critically, we also presented speech at slowed rates, where the spectro-temporal predictions of the two models diverge. Our analyses revealed transient theta phase-locking in regular speech, as predicted by both models. However, for slow speech, we found transient theta and delta phase-locking, a pattern that was fully compatible with the evoked response model but could not be explained by the oscillatory entrainment model. Furthermore, encoding of acoustic edge magnitudes was invariant to contextual speech rate, demonstrating speech rate normalization of acoustic edge representations. Together, our results suggest that neural phase-locking to the speech envelope is more likely to reflect discrete representation of transient information rather than oscillatory entrainment.SIGNIFICANCE STATEMENTThis study probes a highly debated topic in speech perception: the neural mechanisms underlying the cortical representation of the temporal envelope of speech. It is well established that the slow intensity profile of the speech signal, its envelope, elicits a robust brain response that “tracks” these envelope fluctuations. The oscillatory entrainment model posits that envelope tracking reflects phase alignment of endogenous neural oscillations. Here the authors provide evidence for a distinct mechanism. They show that neural speech envelope tracking arises from transient evoked neural responses to rapid increases in the speech envelope. Explicit computational modeling provides direct and compelling evidence that evoked responses are the primary mechanism underlying cortical speech envelope representations, with no evidence for oscillatory entrainment.

Background: Cardiac magnetic resonance imaging (CMR) remains underutilized as an exercise imaging modality, mostly because of the limited availability of MR-compatible exercise equipment. This study prospectively evaluates the clinical feasibility of a newly developed MR-conditional pedal ergometer for exercise CMR Methods: Ten healthy volunteers (mean age 44 ± 16 years) and 11 patients (mean age 60 ± 9 years) with known or suspected coronary artery disease (CAD) underwent rest and post-exercise cinematic 3T CMR. Visual analysis of wall motion abnormalities (WMA) was rated by 2 experienced radiologists, and volumes and ejection fractions (EF) were determined. Image quality was assessed by a 4-point Likert scale for visibility of endocardial borders. Results: Median subjective image quality of real-time Cine at rest was 1 (IQR 1–2) and 2 (IQR 2–2.5) for post-exercise real-time Cine (p = 0.001). Exercise induced a significant increase in heart rate (62 [62–73] to 111 [104–143] bpm, p < 0.0001). Stroke volume and cardiac index increased from resting to post-exercise conditions (85 ± 21 to 101 ± 19 mL and 2.9 ± 0.7 to 6.6 ± 1.9 L/min/m 2 , respectively; both p < 0.0001), driven by a reduction in end-systolic volume (55 ± 20 to 42 ± 21 mL, p < 0.0001). Patients (2/11) with inducible regional WMA at high-resolution post-exercise cine imaging revealed significant coronary artery stenosis in subsequently performed invasive coronary angiography. Conclusion: Exercise-CMR using our newly developed 3T MR-conditional pedal ergometer is clinically feasible. Imaging of both cardiac response and myocardial ischemia, triggered by dynamic stress, is rapidly conducted while the patient is near their peak heart rate.

Percutaneous sacroiliac screw is one of the main methods to treat unstable posterior pelvic ring injury. However, complexity of pelvic anatomical structure increases the difficulty and risk with freehand operation. Besides, S2 screw fixation began to receive attention. The purpose of the current study was to evaluate the safety, accuracy, efficiency and clinical outcome of robot-assisted S2 screw fixation for posterior pelvic ring injury.We reviewed 128 cases of unstable posterior pelvic ring injury treated by percutaneous sacroiliac screw fixation in our hospital from January 2016 to January 2020. All cases were divided into robot-assisted S1 group (RAS1), robot-assisted S2 group (RAS2), freehand group S1 group (FHS1) and freehand group S2 group (FHS2). The mean times of fluoroscopy per screw and adjustment per guide wire were used to evaluate radiation exposure and the efficiency of screw placement, respectively. The final position of the screw was evaluated with postoperative CT to illustrate security and accuracy. 108 patients (84.38%) were followed up for 5~24 months and the Majeed scores were compared among groups.A total of 180 screws were inserted. In comparison of the mean times of fluoroscopy per screw and adjustment per guide wire, RA group was significant less than FH group, further comparison revealed that freehand S2 placement need more fluoroscopy and adjustment times compared with freehand S1 placement, but for robot-assisted procedure, there was no difference between placing S1 and S2. Screw penetration was found in the FHS1(3/48) and FHS2(2/14) and none in RAS1 or RAS2, which means robot-assisted groups were more safety and accurate (P0.001). The mean Majeed score in RAS1 (83.33±13.47) and RAS2 (82.32±11.42) was higher than in FHS1 (80.43±12.25) and FHS2 (75.08±18.47), but this difference failed to reach significant.Compared with the freehand operation, TiRobot increased the safety and accuracy, reduced radiation exposure, and improved the efficiency. TiRobot could reduce the risk of S2 placement and provide a safe and feasible way for clinical practice.

Abstract: In this study, children with vitamin B12 deficiency anemia (V-B12DA) and control subjects were evaluated for erythrocyte glutathione peroxidase, catalase and superoxide dismutase enzyme activities, glutathione, malondialdehyde, serum total sialic acid, total antioxidant status, cobalt, chromium, copper, selenium, vanadium, zinc, iron, lead, magnesium, calcium, sodium, potassium, chloride, phosphorus levels, and the associations of these variables were assessed. The study included 50 children with V-B12DA and 50 control subjects. It was found that the V-B12DA group was significantly lower than the control group, with regard to the mean±the standard error of the mean levels of cobalt (0.089±0.009; 0.058±0.0063 μmol/L, p12 (427.20±21.45; 157.08±3.96 pg/mL, p12DA, significantly linear correlations were observed between cobalt – vitamin B12 (r=0.334; p=0.025), vanadium – MCV (r=0.315; p=0.017), vitamin B12 – MCV (r=−0.297; p=0.026). The findings of the study indicated that the levels of cobalt, vanadium significantly associated with traditional vitamin B12-deficiency parameters. Vitamin B12 and MCV should be measured together with cobalt, vanadium for monitoring the vitamin B12 deficiency anemia.

Clinician perceptions of risk factors influencing biologic complications with dental implants are poorly understood but are relevant to how clinicians manage conversations with patients seeking dental implant therapy.The purpose of this clinician survey was to assess the relative ranking of biologic risk factors with dental implants identified via the history, clinical examination, and clinical decisions and postimplant placement findings.A 10-item survey instrument was tested, refined, and distributed to past participants of the Future Leaders in Prosthodontics (FLIP) workshop series asking for their opinion on the relative ranking of commonly identified risk factors in the areas of patient history, clinical examination, and clinical decisions and postimplant placement findings. Descriptive statistics and frequency tables were developed to identify age groupings, geographic work location, and gender. Group differences with respect to risk factor rankings were identified by using Kruskal-Wallis H tests, and, if significant, paired comparisons were conducted using the Mann-Whitney U test with adjustments for Type I error (α=.05).Significant differences were found by gender, age, and geographic work location. Women viewed "implant placement in site of previous implant loss" (P=.013) and "treated moderate or severe chronic periodontitis" (P=.021) as having significantly greater relative importance than did men, yet men ranked "implant position closer than 1.5 mm from adjacent tooth" (P=.023), "currently using selective serotonin reuptake inhibitor drugs (SSRI)" (P=.001), and "heavy plaque index (PI50%)" (P=.023) as having significantly greater relative importance than did women. Significant differences were found by geographic work location of practice with respondents from Australasia viewing "treatment plan includes prostheses that limit access for cleaning resulting in an increase in bacterial load" as having greater relative importance than did respondents from Africa (P.001) and from South America (P.001). Respondents from South America viewed "implant lacks 2.0 mm of attached tissue around implants" as having greater relative importance than did respondents from Australasia (P.002) or Asia (P.001).Clinicians viewed the relative importance of risk factors for biologic complications with dental implants differently, and those differences varied by clinicians' age, gender, and geographic location of practice.

Economic evaluation of early surgery compared to the endoscopy-first approach in chronic pancreatitis.In patients with painful chronic pancreatitis and a dilated main pancreatic duct, early surgery, as compared with an endoscopy-first approach, leads to more pain reduction with fewer interventions. However, it is unknown if early surgery is more cost-effective than the endoscopy-first approach.The multicenter Dutch ESCAPE trial randomized patients with chronic pancreatitis and a dilated main pancreatic duct between early surgery (surgery within 6 weeks) or the endoscopy-first approach in 30 centers (April 2011 - September 2016). Healthcare utilization was prospectively recorded up to 18 months after randomization. Unit costs of resources were determined, and cost-effectiveness and cost-utility analyses were performed from societal and healthcare perspectives. Primary outcomes were the costs per unit decrease on the Izbicki pain score and per gained quality-adjusted life-year.In total, 88 patients were included in the analysis, with 44 patients randomized to each group. Total costs were lower in the early surgery group but did not reach statistical significance (mean difference €????4,815 (95 per cent bias-corrected and accelerated confidence interval €????13,113 to €3,411; P=0.25). Early surgery had a probability percentage of 88.4% of being more cost-effective than the endoscopy-first approach at a willingness-to-pay threshold of €0 per day per unit decrease on the Izbicki pain score. The probability percentage per additional gained QALY was 75.7% at a willingness-to-pay threshold of €50,000.In patients with painful chronic pancreatitis and a dilated main pancreatic duct, early surgery was more cost-effective than the endoscopy-first approach.

Objective To characterize the multimodal retinal findings of myopic macular pits, a feature of myopic degeneration. Methods A case series of patients with myopic macular pits were studied with multimodal imaging including color fundus photography, fundus autofluorescence (FAF), near infrared reflectance (NIR), spectral domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICG). Results Nine eyes of 6 patients with myopic macular pit were examined. Four patients presented with multiple pits and 3 with bilateral involvement. All pits were localized in a region of severe macular chorioretinal atrophy associated with myopic posterior staphyloma. In 3 eyes, the entrance of the posterior ciliary artery through the sclera was noted at the base of the pit. Schisis overlying the pit or adjacent to the pit was identified in 3 patients. Conclusion Myopic macular pits are an additional rare sign of myopic degeneration, developing in regions of posterior staphyloma complicated by severe chorioretinal atrophy and thin sclera.

Objective To evaluate the long-term structural and microvascular retinal effects of internal limiting membrane peeling for full-thickness macular hole (FTMH) using en face adaptive optics optical coherence tomography (AO-OCT), conventional OCT, and OCT angiography (OCTA). Design Interventional case series. Participants Patients with FTMH treated with vitrectomy, internal limiting membrane peeling, and gas tamponade. Methods Eleven eyes with FTMH that had at least 12 months of postoperative follow-up were enrolled in the study. En face AO-OCT was used to image the superficial retina in the peeled and nonpeeled areas. En face structural OCT was performed to image the inner retinal dimples (IRDs), macular thickness, and retinal nerve fibre layer (RNFL). En face OCTA was used to examine the integrity of the peripapillary nerve fibre layer (NFL) plexus. Results AO-OCT showed RFNL wrapping around the IRDs, and no obvious peripapillary NFL plexus dropout was seen with OCTA. Scattered hyper-reflective dots were observed on the surface of the peeled retina in all patients imaged with AO-OCT. No significant differences were found in IRD number (91.5 ± 24.4 versus 77.2 ± 14.7; P = 2.07), IRD proportionate area (8.36 ± 3.34 versus 7.53 ± 2.60; P = 0.159), or macular thickness between the 6- and 12-month (or greater) postoperative visits. Conclusion IRDs do not to progress beyond 6 months postoperatively, and no obvious damage to RFNL and peripapillary NFL plexus was detected. Hyper-reflective dots on the surface of the retina suggestive of possible Muller cell reactive gliosis were identified with AO-OCT.

Objective This study aimed to analyze our outcomes of primary premaxillary ostectomy and setback combined with lip adhesion as the first stage in repair of the bilateral cleft lip with fly-away premaxilla. Methods This retrospective study included all patients who required primary premaxillary setback by a single surgeon to achieve successful lip repair between 2011 and 2017 at a tertiary children's hospital. All patients had bilateral cleft lip and complete cleft palate with significant premaxillary protrusion. All patients either had failed presurgical orthodontic manipulation or were thought to be poor candidates because of the rigidity of the premaxilla on clinical examination. Patient data were obtained from review of medical records and photographs. Surgical technique is described. Results Eleven patients with bilateral cleft lip, all of whom also had complete cleft palate, underwent primary premaxillary setback and lip adhesion at an average age of 8.2 months. The mean follow-up was 1.9 years (range, 139 days to 4.5 years). All patients subsequently completed formal lip repair, of which 10 have undergone palatoplasty. Serial photography documented stable premaxillary position and successful lip repair within the follow-up time frame. No patient had postoperative premaxillary instability or vascular compromise. One patient had dehiscence of the lip adhesion requiring reoperation. Conclusions Primary premaxillary ostectomy and setback allows for successful staged formal lip repair in patients with bilateral cleft lip and palate who have failed presurgical infant orthopedics. Further research is required regarding long-term follow-up with respect to midfacial growth.

Cystic hydatid disease or cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval cyst stage of the tapeworm Echinococcus granulosus. Concomitant presence of CE and hepatocellular carcinoma (HCC) is a rare clinical scenario. A 70-year-old male patient presented with acute abdominal pain to the surgical outpatient department. On evaluation, a cystic lesion with solid components and free fluid in the abdomen was observed, which led to multiple differentials in the working diagnosis. A CT showed the mass to have a delayed enhancement. Surgical exploration revealed a partially ruptured hydatid cyst with daughter cysts in the abdominal cavity and a solid-component mass lesion. We proceeded with a right partial hepatectomy. Pathological evaluation revealed a pale mass lesion with a large collapsed cyst. HCC with unusual dense fibrillar fibrosis and cystic interface with normal parenchyma was observed. This case connects the multimodal assessment of radiology, surgery and pathology.

Background Five to ten percent of the global population have unruptured intracranial aneurysms, and ruptured brain aneurysms cause approximately 500,000 deaths a year. Flow-diverting stent treatment is a less invasive intracranial aneurysm treatment that induces aneurysm thrombosis. The imaging characteristics of a novel primarily bioresorbable flow-diverting stent (BFDS) are assessed in comparison to the leading metal stent using fluoroscopy, CT, and MRI. Methods X-ray/fluoroscopic images of stents were taken using a human cadaveric skull model. CT and MRI were acquired using silicone flow models of residual aneurysms. Images were analyzed with Likert scales in anonymous surveys by neurointerventionalists. Quantitative measurements of radiographic density (CT) and artifact boundary size (CT & MRI) were also obtained. Results Visibility of the BFDS on X-ray was less than the metal stent but deemed adequate for deployment and intraprocedural assessment. The metal stent was more radiopaque than the BFDS on CT, but qualitative assessment was not significantly different for the two stents. MRI imaging was significantly better using the BFDS in terms of overall artifact and intraluminal assessment. Conclusions The BFDS has adequate visualization on X-ray/fluoroscopy and should be clinically acceptable for fluoroscopic deployment. On MRI, there is less quantitative artifact as well as overall improved qualitative assessment that will allow for more detailed non-invasive imaging follow-up of treated aneurysms, potentially reducing the need for digital subtraction catheter angiography.

A 74-year-old woman presents with a 7-day history of increasing lower abdominal pains and reduced bowel movements; resulting in absolute constipation.Twenty-four hours prior to admission she also had symptoms of nauseous and significant abdominal distention. Her past medical history included; diverticulitis, type 2 diabetes, hypercholesterolemia, an ultrasound scan in 2005 confirming gallstones, but no previous abdominal surgery.She was initially treated for bowel obstruction and a CT arranged. CT showed a 4.5 cm gallstone in mid-sigmoid colon and a cholecystocolonic fistula. She was booked for colonoscopy±laparotomy, but on the morning of her planned procedure she repeatedly opened her bowels. Subsequent colonoscopy was negative and repeat CT confirmed the stone was no longer within the gastrointestinal tract.

Most patients with cystic fibrosis (CF) develop multisystemic clinical manifestations, the minority having mild or atypical symptoms. We describe an adolescent with chronic cough and purulent rhinorrhoea since the first year of life, with diagnoses of asthma, allergic rhinitis and chronic rhinosinusitis. Under therapy with long-acting bronchodilators, antihistamines, inhaled corticosteroids, antileukotrienes and several courses of empirical oral antibiotic therapy, there was no clinical improvement. There was no reference to gastrointestinal symptoms. Due to clinical worsening, extended investigations were initiated, which revealed Pseudomonas aeruginosa in sputum culture, sweat test with a positive result and heterozygosity for F508del and R334W mutations in genetic study which allowed to confirm the diagnosis of CF. In this case, heterozygosity with a class IV mutation can explain the atypical clinical presentation. It is very important to consider this diagnosis when chronic symptoms persist, despite optimised therapy for other respiratory pathologies and in case of isolation of atypical bacterial agents.

Neonatal lupus is an uncommon entity. The main manifestations are cutaneous and cardiac. It is caused by transplacental passage of maternal antibodies (anti-Ro/SSA or anti-La/SSB), and the diagnosis is made by its detection in the mother or child. The authors present a case of a 4-month-old female infant, with a cutaneous eruption since she was 2 months old. She had no relevant personal or family history. Analytically she had an increase in liver enzymes. The histological aspect of the skin biopsy led to an autoimmunity study on the mother and infant, both of which had positive anti-Ro/SSA antibodies, confirming the diagnosis of neonatal lupus. Cardiological study was normal. The skin lesions resolved during the first year of life. Skin lesions are the most frequent non-cardiac clinical manifestation of neonatal lupus, and they are self-limited. When there is no family history, nor cardiac involvement, the diagnosis can be challenging.

Brachial plexus injury is a rare but potentially serious complication of laparoscopic surgery. Loss of motor and/or sensory innervation can have a significant impact on the patient’s quality of life following otherwise successful surgery. A 38-year-old underwent elective laparoscopic management of severe endometriosis during which she was placed in steep head-down tilt Lloyd-Davies position for a prolonged period. On awakening from anaesthesia, the patient had no sensation or movement of her dominant right arm. A total plexus brachialis injury was suspected. As advised by a neurologist, an MRI brachial plexus, nerve conduction study and electromyography were requested. She was managed conservatively and made a gradual recovery with a degree of residual musculocutaneous nerve neuropathy. The incidence of brachial plexus injury following laparoscopy is unknown but the brachial plexus is particularly susceptible to injury as a result of patient positioning and prolonged operative time. Patient positioning in relation to applied clinical anatomy is explored and risk reduction strategies described.

Functional metastatic pheochromocytoma (PCC) is a very rare tumour and cytoreductive adrenalectomy with oligo metastatectomy is recommended in cases of low tumour burden. We report a rare case of metastatic PCC with an incidentally detected suspicious nodule seen on the anterior surface of the right lobe of the liver. The adrenal and the lesion were excised and sent for histopathology which was reported as a metastasis from PCC. This lesion was not visualised preoperatively on DOTA-PET-CT, highlighting the importance of keeping a low threshold for suspicion of metastasis in abnormal lesions and taking a biopsy during surgery. Inspection of the liver and rest of the abdomen for any abnormality should be done even when operating for any apparently benign lesions.

A 60-year-old man presented with severe abdominal pain, two episodes of massive haematemesis and chest discomfort. CT angiography showed a saccular aneurysm of the juxtaphrenic aorta with possible oesophageal erosion. Upper GI endoscopy revealed external compression of the lower oesophagus—near total luminal obstruction with impending rupture of the aortic aneurysm. Emergency aneurysmal repair by interposition grafting using 20 mm Dacron graft with oesophageal–gastric reconstruction done. Postoperative period was uneventful

Mycotic aneurysms are rare and if left untreated, can have devastating outcomes. In this case, a 72-year-old man presented to hospital with fevers, night sweats and abdominal pain. A CT scan revealed the development an infrarenal pseudoaneurysm over the course of 8 weeks, increasing from 2.8 cm to a 3.1 cm. The aneurysm was not present on a CT scan performed 6 months earlier. The patient underwent an emergency endovascular repair of the aortic aneurysm (EVAR) and was placed on broad-spectrum antibiotics. Intra-aortic blood cultures aspirated adjacent to the aneurysm and tissue biopsy confirmed tuberculosis bovis as the cause of the mycotic aneurysm. The patient had been treated with intravesical BCG for transitional cell carcinoma of the bladder several months prior. The patient was treated with an extended course of antituberculosis medication. He recovered well and was back to his baseline function within weeks.

We report a case of a 60-year-old man who struggled with frequent migraines for 12.5 years, which were refractory to all conventional therapies. Six months before initial consultation, these migraines become chronic. The patient was then advised to follow the Low Inflammatory Foods Everyday (LIFE) diet, a nutrient-dense, dark green leafy vegetable-rich, whole food plant-based diet. Within 2 months, his headache frequency declined from 18 to 24 headache days per month to 1, and he discontinued his preventive and abortive migraine medications. After 3 months, the patient had no headaches. These results far exceed the goal of migraine treatment with medication, which is to reduce migraine frequency by >50% per month. In addition, the results were durable; this patient has been migraine-free for 7.5 years. Serum beta-carotene more than tripled after the patient started the LIFE diet, consistent with its high content of dark green leafy vegetables. Weight, high-sensitivity C-reactive protein (hsCRP), complete blood count (CBC), hydration status, sodium and other electrolytes remained constant throughout the study.

A 36-year-old man with peptic ulcer disease presented to the emergency department with a 2-day history of haemoptysis and cough. Though he had no prior pulmonary symptoms, he noted progressive chest tightness and shortness of breath. He had no fever or night sweats. Vital signs were afebrile and

A young woman presented to neurology with a 1 month history of progressive diplopia on lateral gaze and a 1 week history of headaches. On examination she was found to have complex ophthalmoparesis with binocular horizontal diplopia, failure of abduction bilaterally and limited upgaze with convergence-retraction nystagmus. The rest of the neurological examination was normal. She was admitted for investigations: blood, CT brain, MR brain and lumbar puncture results were normal. Anti-GD1a antibodies were strongly positive; anti-GM1, anti-GM2 and anti-GD1b were also positive. On follow-up 3 weeks later, the complex ophthalmoplegia persisted. It was decided to treat with intravenous immunoglobulins (IVIgs) with good response but recurrence at 2 weeks post infusion. She was treated with 4 weekly IVIg courses and remains responsive and controlled over 1 year since presentation but becomes symptomatic in the week running up to each dose; thus, disease modifying treatment is currently being considered.

A 75-year-old man presented with a 3-week history of melaena and right upper quadrant pain. This was on a background of significant alcohol intake and a complex medical history. He was haemodynamically unstable with investigations indicating a new iron-deficiency anaemia. After resuscitation, urgent intervention was required under general anaesthesia. This involved a triple phase abdominal CT, followed by emergency oesophagogastroduodenoscopy. This revealed deep ulceration with extension to the pancreatic head and common bile duct. There was also evidence of pneumobilia on CT, secondary to a choledochoduodenal fistula. Treatment encompassed an invasive and medical approach. Following treatment, the patient was stable, with follow-up endoscopy exhibiting good duodenal mucosal healing.

An autoamputated ovary (AO) is an extremely rare circumstance with a few reports in the literature. We present a case of a 3-month-old girl with a history of vague abdominal symptoms as well as a known ovarian mass, which was initially suspected to be benign and regressing. On laparoscopy for pain and obstructive symptoms, she was found to have an AO. The pathology was consistent with necrotic and torsed ovarian tissue with superimposed infection and possibly a cystic non-malignant teratoma. AOs are thought to originate from a torsion and are typically diagnosed incidentally. This is an interesting case of an AO causing a partial small bowel obstruction.

Iliopsoas abscesses (IPA) are uncommon, with an associated mortality rate of up to 20%. We describe the case of a 55-year-old man war veteran who presented with an unusual cause of IPA secondary to retained foreign body (FB). His initial trauma 30 years before was a result of a blast injury with shrapnel penetration suffered after inadvertently driving over a landmine as an ambulance driver in a conflict region. A CT scan was performed, revealing a 13 mmx8 mm radio-opaque FB within the right psoas at the level of the fifth lumbar vertebra with a surrounding collection. Subsequent open surgical exploration removed two gravel fragments. Given the knowledge of a traumatic blast injury with retained FB and repeated episodes of sepsis, surgical exploration is warranted. To our knowledge, this is the first case of recurrent IPA secondary to a retained FB from a historical trauma.

Hepatic artery pseudoaneurysm (HAP) is mostly encountered secondary to trauma or iatrogenic causes. HAP associated with cholangitic liver abscess is a rare complication. We present a case of gallstone disease and choledocholithiasis who developed moderate cholangitis and a liver abscess. A small HAP was detected incidentally on a biphasic CT done to evaluate the biliary system. Repeat CT after management with endoscopic retrograde cholangiopancreatography and antibiotics showed resolution of cholangitic abscess with spontaneous thrombosis of HAP.

Disseminated histoplasmosis is a life-threatening condition in immunocompromised patients. The majority of healthy persons have benign disease not requiring treatment. However, in persons living with HIV, mortality is high and accurate diagnosis is paramount. We present a case of a 48-year-old HIV-positive woman who presented with haematuria and flank pain. She had a history of recurrent urinary tract infection and nephrolithiasis with obstructive hydronephrosis. During cystoscopy, a bladder lesion was found. Pathological evaluation demonstrated abundant intracellular organisms with apparent budding. Subsequent urine histoplasma antigen was negative. Given the high index of suspicion for histoplasmosis based on the surgical pathology findings and epidemiological history, the patient was started immediately on antifungal therapy. One week later, PCR results of the bladder lesion confirmed the presence of Histoplasma capsulatum. This case highlights a rare presentation of genitourinary histoplasmosis and the utility of surgical pathology evaluation and PCR for diagnosis.

Torcular dural sinus malformations (tDSMs) represent a rare subset of paediatric cerebrovascular malformations and are often diagnosed antenatally via ultrasound. The management of these in utero lesions remains controversial as previous studies suggested elective termination of the pregnancy because of their presumably high mortality and severe long-term morbidity. However, more recent evaluations have suggested that the overall prognosis for infants harbouring these lesions may be much better than previously believed. As such, we present the case of a neonate with a giant tDSM, diagnosed in utero, who was treated postnatally via staged transarterial and transvenous embolisation to alleviate worsening obstructive hydrocephalus and brainstem compression. We provide details regarding the surgical approach and long-term neurological outcomes for this patient. To the best of our knowledge, this is one of the largest reported tDSM presented in the literature.

Various bowel preparation agents have been developed for effective and safe bowel cleansing before colonoscopy. Polyethylene glycol (PEG) is widely used in the elderly. A 2 L PEG solution with ascorbic acid (PEG-Asc) was developed to reduce the volume of standard 4 L PEG. Several cases of

A 67-year-old man was referred to the renal team following an episode of acute kidney injury on a background of chronic kidney disease. He had a 9-year history of steroid-sensitive arthritis, epigastric pain and isolated submandibular gland enlargement. He was noted to have a raised eosinophil count, total serum protein and total immunoglobulin G4 (IgG4) level as well as a serum hypocomplementaemia. A renal biopsy showed a tubulointerstitial nephritis with lymphoplasmacytic infiltrates, fibrosis and IgG4-positive plasma cells on immunohistochemistry. A diagnosis of IgG4-related disease was made based on clinical presentation and pathology. Renal function improved with glucocorticoids and the patient was successfully transitioned to azathioprine as a steroid-sparing agent.

A 53-year-old woman without medical problems presented with 5-month history of dizziness, difficulty speaking, severe ataxia, which worsened a day before admission to inability to stand unsupported. An extensive workup was initiated to find the cause of ataxia. The laboratory investigations and imaging of the brain and whole spine revealed no lesions. She was found to have autoimmune thyroiditis, positive coeliac disease antibodies without clinical features and vitamin D deficiency. No intravenous steroids or immunosuppressive therapy was given. Cerebrospinal fluid showed lymphocytic pleocytosis. The workup for the cause of severe ataxia revealed an oropharyngeal lesion with cervical lymph nodes, and the biopsy showed classical Hodgkin’s lymphoma of mixed cellularity. She was treated with chemotherapy followed by radiation therapy and made a remarkable recovery, and currently, she is in remission without distant metastases, 5 years after the initial diagnosis. Her neurological status improved, and she remained with mild ataxia.

Few cases of programmed death-ligand 1 inhibitor-induced scleroderma have been reported and their clinical features remain unpublished. Optimal management is, therefore, unknown and an autoantibody association has yet to be identified. We present the case of a female in her 60s who developed skin thickening after starting atezolizumab for metastatic non-small cell lung cancer. Skin biopsy 7 months after symptom onset showed histological changes consistent with scleroderma. Anti-PM/SCL-75 antibody was positive. Atezolizumab was discontinued and treatment was started with mycophenolate mofetil. After 5 months, she experienced mild improvement in skin thickening. Earlier identification of this complication may limit morbidity in this disease process, which otherwise has limited treatment options. In suspected cases, obtaining scleroderma-associated autoantibodies may help with earlier diagnosis.

Renal cell carcinoma (RCC) frequently presents with osseous metastasis, predominantly lytic and prone to pathological fracture. The metastatic lesion in the extremity presents with local swelling, pain and immobility due to pathological fracture. The solitary or oligometastatic lesions should be treated with curative intent, which can help the patient to lead a more prolonged and disability-free life. The RCCs and their metastases are hypervascular with an exuberant arterial supply. Surgery can lead to uncontrolled life-threatening haemorrhage. Preoperative transarterial embolisation reduces tumour vascularity significantly and reduces intraoperative blood loss. We present a 46-year-old male patient with solitary hypervascular metastatic recurrence of RCC with a pathological femoral fracture with an infeasible initial surgery due to profuse haemorrhage. He was successfully treated by preoperative transarterial embolisation, followed by surgical resection and implantation of a megaprosthesis. Multidisciplinary management reduces patient morbidity and mortality with successful treatment in solitary hypervascular metastasis from RCC.

Liver involvement in Graves’ disease can be seen as a part of autoimmune process or rarely, due to the direct effects of thyrotoxicosis on liver. Hyperthyroidism can also have gastrointestinal manifestations like frequent bowel movements, diarrhoea, even malabsorption with steatorrhoea. We report a 36-year-old man with hyperthyroidism, presenting with cholestatic jaundice and persistent small bowel diarrhoea. He was diagnosed to have Graves’ disease and after ruling out more common causes, the cause of cholestatic jaundice was supposed to be Graves’ disease. Considering this possibility, the patient was started on treatment with carbimazole. As patient’s thyroid function tests started improving, he showed significant clinical and biochemical improvement from liver point of view as well.

The uterine myometrium is the rarest location for an ectopic pregnancy resulting in the so-called ‘intramural or intramyometrial ectopic pregnancy’. It presents a particular diagnostic and therapeutic challenge for the treating physician. If passed undiagnosed can lead to life-threatening uterine rupture, which may warrant hysterectomy, leaving the woman with irreversible infertility. Different treatment modalities have been proposed for the management of this condition. In this case report, we are describing a rare case of intramural ectopic pregnancy and reporting the use of hysteroscopy for the surgical management of this case for the first time in the literature.

A 30-year-old man was referred by a general ophthalmologist for retina examination owing to his high myopia status. His presenting visual acuity in the right eye was 6/6 with a refraction of −2.75 dioptre sphere (DS), −2.75 dioptre cylinder (DC) at 170° and that in the left eye was 6/9 with a