Search

Objective: To evaluate the effects of uncoupling protein (UCP) 1, UCP2 and UCP3 gene variants on body composition and metabolic changes in response to chronic overfeeding and the recovery after the period of overfeeding. Subjects and design: Twenty-four normal weight men (21±2 y), who constituted 12 pairs of identical twins, ate a 4.2 MJ/day energy surplus, 6 days a week, during a period of 100 days. The subjects were asked to return to the laboratory for testing at 4 months and for a final examination 5 y after completion of the overfeeding protocol. Methods: Resting metabolic rate (RMR) measurements were performed before and after overfeeding. A 4.2 MJ test meal was consumed, after which calorimetric measurements were continued for 240 min. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Polymorphisms were typed by PCR and PCR-RFLP-techniques. Thyroid stimulating hormone (TSH) concentrations after a thyrotropin releasing hormone (TRH) injection were measured by radioimmunoassay (RIA). Results: The changes in body weight and adiposity were not different between UCP1 Bcl I, UCP2 alanine to valine (A55V), UCP2 insertion/deletion (I/D) or UCP3 Rsa I genotypes. However, the recovery from overfeeding was worse among G-allele carriers of the UCP1 Bcl I, I allele non-carriers of the UCP2 I/D, AV heterozygote subjects of the UCP2 A55V and CC subjects of the UCP3 Rsa I polymorphisms. RMR was lower both before (P=0.01) and after (P=0.001) overfeeding in subjects with the CC genotype of the UCP3 Rsa I polymorphism. Moreover, after overfeeding, the UCP2 A55V heterozygote and UCP3 Rsa I CC homozygote subjects had significantly higher respiratory quotient (RQ) values at rest (P

Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14–1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12–1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08–1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00–4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation. European Journal of Clinical Nutrition (2001) 55, 1000–1007

Objective: To demonstrate sexual dimorphism in serum leptin levels not only during puberty, but also in childhood in Japan. Design: Cross-sectional study. Setting: Hamamatsu-Hokuen study in Japan. Subjects: Body weight and height were measured in normal-weight Japanese children and adolescents (143 boys, 178 girls), and 161 boys and 129 girls whose percentage of overweight for the standard (%Wt) was more than+25%. Serum leptin levels were compared with %Wt. Subjects were divided into group 1 (6–10 y of age) and group 2 (11–15 y of age) according to their age. Results: In overweight subjects, leptin was more highly correlated with %Wt in boys of group 2 (r=0.67, P

Females have long been underrepresented in preclinical research and clinical drug trials. Directives by the U.S. National Institutes of Health have increased female participation in research protocols, although analysis of outcomes by sex remains infrequent. The long-held view that traits of female rats and mice are more variable than those of males is discredited, supporting equal representation of both sexes in most studies. Drug pharmacokinetic analysis reveals that, among subjects administered a standard drug dose, women are exposed to higher blood drug concentrations and longer drug elimination times. This contributes to increased adverse drug reactions in women and suggests that women are routinely overmedicated and should be administered lower drug doses than men. The past decade has seen progress in female inclusion, but key subsequent steps such as sex-based analysis and sex-specific drug dosing remain to be implemented.

Aims: To determine the efficacy of XPro1595 to improve pathophysiological and functional outcomes in a mouse model of traumatic brain injury (TBI). Background: Symptoms associated with TBI can be debilitating, and treatment without off-target side effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI. Objectives: Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation and dendritic plasticity and associated functional impairments. Methods: Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically relevant window (60 minutes post-injury). The animals were assessed for differences in neurological function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as neuronal degeneration and plasticity. Results: We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology’s within the hippocampus consistent with the observed neurological outcomes, including glial reactivity, enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity (spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were prevented in mice treated with XPro1595. Conclusion: Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use in patients with TBI.

Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.

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.

This review will detail the embryology and morphology of the heart. We will begin with the heart's origin in the lateral plate mesoderm of the early embryo, review its fusion into a linear heart tube, followed by looping and remodeling to create a four-chambered organ with pulmonary and systemic venous inflow and pulmonary and systemic arterial outflow. We will discuss important concepts in heart development at genetic, cellular, and physiologic levels and review some key experimental models and methods important to the study of cardiac development. This review will also serve to introduce some of the congenital heart defects that can result from abnormalities in development and some of the genetic syndromes that are linked to congenital heart defects.

• 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.

• Papulopustular lesions on the palms and/or soles in the first month of life likely represent a self-limited inflammatory process such as eosinophilic pustular folliculitis or infantile acropustulosis – but scabies should be ruled out. • Neonatal acne (aka cephalic pustulosis) is typically multifactorial and self-limited. Treatment is not necessary but topical agents aimed at reduction of the commensal yeast Malassezia can be beneficial. • Evidence suggests that early use of emollients in infants at risk of developing atopic dermatitis may prevent later disease. • Subcutaneous fat necrosis of the newborn is generally benign and self-limited but when extensive can cause hypercalcemia.

Thrombocytopenia is, after anemia, the most frequent hematological problem among sick neonates. In this population, thrombocytopenia has traditionally been defined as a platelet count 9 /L, and has been classified as mild (100–150 × 10 9 /L), moderate (50–99 × 10 9 /L), and severe ( 9 /L). However, large population-based studies have shown that platelet counts increase with advancing gestational age, and platelet counts between 100 and 150 × 10 9 /L are more frequent among otherwise healthy extremely preterm infants than among full term neonates or older children. This suggests that different definitions of thrombocytopenia and thrombocytosis should be applied to preterm infants. The diagnostic approach to a thrombocytopenic neonate is facilitated if the thrombocytopenia is categorized as “early onset” (within the first 72 hours of life, usually secondary to congenital or intrauterine abnormalities) or “late onset” (after 72 hours, usually due to acquired conditions). Importantly, infection/sepsis should always be considered near the top of the differential diagnosis, as any delay in diagnosis and treatment can have life-threatening consequences. While in vitro studies have clearly shown that neonatal platelets are hyporesponsive to most agonists, this platelet hyporeactivity is well compensated by factors in neonatal blood that increase clotting (i.e. high hematocrit, high VWF concentrations), resulting in adequate primary hemostasis. The risk of bleeding in thrombocytopenic neonates is poorly predicted by the platelet count; gestational age

• An understanding of thyroid embryogenesis and the physiology of the thyroid gland in the perinatal period is important for proper interpretation of abnormal laboratory results and initiation of appropriate treatment. • Appropriate thyroid hormone function is essential for normal neurodevelopment in infancy and childhood. Hypothyroidism in the first year of life can result in significant deleterious effects on growth and neurologic injury. • Delay in treatment of congenital hypothyroidism (CH) is the most common preventable cause of mental retardation. • Neonatal screening can provide early diagnosis and can prevent delays in treatment. Newborn screening methods differ and may possibly miss rare forms of congenital hypothyroidism. • Eighty-five percent of cases of permanent CH are associated with abnormal development of the thyroid gland. • In preterm newborns, thyroid hormone levels may fall because of immaturity of the thyroid gland, but these changes may be exacerbated by complications of prematurity. • Thyroid metabolism can be affected by exogenous sources of iodine, dopamine infusions, blood transfusion, and glucocorticoid treatment. • The clinical manifestations of Graves disease in the newborn include irritability, flushing, diarrhea, vomiting, tachycardia, hypertension, poor weight gain, thyroid enlargement, and exophthalmos. • There is concern for neurologic damage in infants with hemangiomas when hypothyroidism is occult and untreated.

Chronic diffuse lung diseases involve a spectrum of nonneoplastic inflammatory conditions that affect the lung parenchyma. This chapter reviews the spectrum of disease including idiopathic interstitial pneumonias, pulmonary manifestations of systemic collagen vascular disease, diffuse eosinophilc lung disease, drug-associated lung disease, diffuse granulomatous lung disease, and a variety of miscellaneous diseases that defy classification. Individual entities are reviewed, followed by a section highlighting a practical approach to the four most common patterns of injury encountered in practice.

Background Thumb carpometacarpal (CMC) joint arthroplasty is a common procedure in the surgical management of symptomatic thumb basal joint arthritis. Following trapeziectomy, a number of suspensionplasty techniques are often used, but limited comparative evidence exists between these techniques. The central aim of this study was to prospectively compare the outcomes of 2 suspensionplasty techniques following trapeziectomy: suture button (TightRope) versus ligament reconstruction and tendon interposition (LRTI). Methods Prospective data were collected on 112 consecutive patients with Eaton stage III-IV thumb CMC arthritis who underwent open trapeziectomy and suspensionplasty. There were 53 LRTI and 59 TightRope suspensionplasty procedures. Outcomes were measured using the Quick Disabilities of the Arm, Shoulder, and Hand ( QuickDASH) questionnaire, Visual Analogue Scale (VAS) for pain, radiographic analysis, and lateral pinch strength. Patient demographic data and complications were also recorded. Results Patients undergoing TightRope suspensionplasty had significantly higher trapeziometacarpal index and thus less subsidence than the LRTI group at 2 weeks (0.22 vs 0.17 [ P < .0001]) and 3 months (0.17 vs 0.15 [ P < .05]) postoperatively. TightRope suspensionplasty also had a significantly lower QuickDASH score at 2 weeks (64.7 vs 74.6 [ P < .05]), 3 months (20.7 vs 32.5 [ P < .05]), and 1 year postoperatively (7.57 vs 21.5 [ P < .05]) compared with the LRTI group. However, there was no difference in VAS pain, lateral pinch strength, reoperation, or complications at any time point between groups. Conclusions Thumb CMC joint arthroplasty performed with a TightRope suspensionplasty versus LRTI yielded short-term improved resistance to subsidence, long-term greater improvement in clinical outcome by QuickDASH, and no difference in pain or complication rates.

• 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).

• Infants born with ambiguous genitalia or nonpalpable testes need to be evaluated for congenital adrenal hyperplasia as it can be life threatening. • Adrenal steroid levels vary with gestational age. • Adrenal insufficiency should be treated with hydrocortisone to avoid adrenal crisis. High doses of hydrocortisone contain mineralocorticoid activity.

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.

A term large-for-gestational-age neonate was born via an uncomplicated normal vaginal delivery at a peripheral hospital. The neonate was referred to our tertiary centre due to concerns regarding the appearance of the right hand. On examination at 6 hours of life there was cyanotic discolouration

Myasthenia gravis (MG) is an autoimmune condition affecting the neuromuscular junction characterised by weakness and fatiguability, carrying a high morbidity if treatment is delayed. A clear association with thymoma has led to management with thymectomy as a common practice, but MG presenting post-thymectomy has rarely been reported. We present a case of an 82- year-old woman developing fatigue, ptosis and dysarthria 3 months after thymectomy. After a clinical diagnosis of MG was made, she responded well to prompt treatment with prednisolone and pyridostigmine. Her anti-acetylcholine receptor antibody (anti-AChR) subsequently came back positive. Our systematic review reveals that post-thymectomy MG can be categorised as early-onset or late-onset form with differing aetiology, and demonstrated correlation between preoperative anti-AChR titres and post-thymectomy MG. The postulated mechanisms for post-thymectomy MG centre around long-lasting peripheral autoantibodies. Clinicians should actively look for MG symptoms in thymoma patients and measure anti-AChR preoperatively to aid prognostication.

Chemotherapy can result in toxic side effects in the brain. Intake of marine-based omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), alter brain fatty acids, potentially improving brain function. However, it is unclear if alpha-linolenic acid (ALA), the plant-based n-3, affects brain PUFAs during chemotherapy. The objective of this study was to examine the effects of dietary ALA, EPA and DHA, with high or low sucrose, on brain PUFAs in a mouse model of chemotherapy. Secondarily, the use of liver PUFAs as surrogate measures of brain PUFAs was examined. Lipid peroxidation (4-HNE) and neurotrophic markers (BDNF) were assessed. Female C57Bl/6 mice (n = 90) were randomized to 1 of 5 diets (high EPA + DHA/high or low sucrose, high ALA/high or low sucrose, or control with no EPA + DHA/low ALA/low sucrose) and injected with doxorubicin-based chemotherapy or saline. Brain EPA and DHA were greater (p < 0.0001) with high EPA + DHA diets, regardless of sucrose; there were no significant differences in brain PUFAs between high ALA diets and control. Chemotherapy-treated mice had higher brain and liver DHA (p < 0.05) and lower brain and liver linoleic acid (p < 0.0001). Brain n-3 and n-6 PUFAs were strongly correlated with liver n-3 (r = 0.8214, p < 0.0001) and n-6 PUFAs (r = 0.7568, p < 0.0001). BDNF was correlated with brain total PUFAs (r = 0.36; p < 0.05). In conclusion, dietary ALA in proportions approximately two times greater than consumed by humans did not appreciably increase brain n-3 PUFAs compared to low ALA intake. Liver PUFAs may be a useful surrogate marker of brain PUFAs in this mouse model.

The lateral step-down test is used to appraise movement quality in patients with patellofemoral pain (PFP), however, it is unclear if reliability of the test is affected by physical therapist experience.Determine if there is a difference in reliability between 'experienced' and 'novice' physical therapists appraising movement quality of patients with PFP during the lateral step-down test.Three 'experienced' and 3 'novice' physical therapists analyzed movement quality of 22 participants [mean age (SD) 28.25 (6.5) years] with PFP. Physical therapists viewed two-dimensional videos of participants performing the lateral step-down test and appraised the quality with a score (0-1 = 'good'; 2-3 = 'fair', and 4-5 = 'poor') at baseline and 1 week. Inter- and intra-rater reliability were calculated with kappa and percent agreement. Differences between the groups were assessed with the chi-square test with an a priori alpha level of0.05.Inter- and intra-rater reliability ranged from fair to moderate (ĸ = 0.40-0.65). There was no difference in reliability between 'experienced' and 'novice' physical therapists at baseline (There was no difference in reliability between 'experienced' and 'novice' physical therapists using categories to appraise movement quality during the lateral step-down test for patients with chronic PFP.

BACKGROUND: The association between obesity (body mass index (BMI) ≥ 30 kg/m(2)) and pattern of medication use during pregnancy in the United States is not well-studied. Higher prepregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. OBJECTIVES: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. METHODS: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. RESULTS: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19–29.9 kg/m(2)), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. CONCLUSION: Our findings suggest that pre-pregnancy obesity in otherwise healthy women is associated with a higher use of only selected medications (such as diabetes medications and progesterone) during pregnancy, while the intake of other more common medication types such as analgesics, antibiotics, and antacids does not vary by pre-pregnancy obesity status. As medication safety information for prenatal consumption is insufficient for many medications, these findings highlight the need for a more in-depth examination of factors associated with prenatal medication use.

Objective To compare outcomes after surgery between patients who were not prescribed opioids and patients who were prescribed opioids. Summary of background data Postoperative opioid prescriptions carry significant risks. Understanding outcomes among patients who receive no opioids after surgery may inform efforts to reduce these risks. Methods We performed a retrospective study of adult patients who underwent surgery between January 1, 2019 and October 31, 2019. The primary outcome was the composite incidence of an emergency department visit, readmission, or reoperation within 30 days of surgery. Secondary outcomes were postoperative pain, satisfaction, quality of life, and regret collected via postoperative survey. A multilevel, mixed-effects logistic regression was performed to evaluate differences between groups. Results In a cohort of 22,345 patients, mean age (standard deviation) was 52.1 (16.5) years and 13,269 (59.4%) patients were female. About 3175 (14.2%) patients were not prescribed opioids, of whom 422 (13.3%) met the composite adverse event endpoint compared to 2255 (11.8%) of patients not prescribed opioids (P = 0.015). Patients not prescribed opioids had a similar probability of adverse events {11.7% [95% confidence interval (CI) 10.2%-13.2%] vs 11.9% (95% CI 10.6%-13.3%]}. Among 12,872 survey respondents, patients who were not prescribed an opioid had a similar rate of high satisfaction [81.7% (95% CI 77.3%-86.1%) vs 81.7% (95% CI 77.7%-85.7%)] and no regret [(93.0% (95% CI 90.8%-95.2%) vs 92.6% (95% CI 90.4%-94.7%)]. Conclusions Patients who were not prescribed opioids after surgery had similar clinical and patient-reported outcomes as patients who were prescribed opioids. This suggests that minimizing opioids as part of routine postoperative care is unlikely to adversely affect patients.

Objective Intra-procedural WEB device migration is a scarcely reported complication that necessitates prompt intervention. Case Presentation Endovascular treatment of two broad necked flow-related aneurysms was planned aided by WEB-SL (Woven EndoBridge-single layer) devices in a 71-year-old female with known left temporal arteriovenous malformation. Inadvertent distal migration occurred while performing a control angiogram with an automated iodine injector. Immediate retrieval was successfully performed using a Solitaire stent-retriever. Conclusion To our knowledge, we report for the first time the successful retrieval of a distally migrated WEB using a stent-retriever device.

Objective To evaluate pre - to post-season differences in individual subtests of the Visio-Vestibular Examination (VVE) in healthy middle and high school athletes. Methods This prospective cohort study recruited participants from a private suburban United States secondary school. Participants completed a demographic questionnaire prior to the start of their season. A proxy for head impact exposure was estimated by incorporating previously published head impact frequencies by team and sport. The VVE was completed pre - and post-season and consisted of 9 subtests: smooth pursuit, horizontal/vertical saccades and gaze stability, binocular convergence, left/right monocular accommodation, and complex tandem gait. Generalized estimating equations were employed to assess the relative risk of an abnormal VVE outcome based on testing session (pre - vs. post-season). Results Participants included middle and high school athletes (n = 115; female = 59 (51.3%); median age at first assessment = 14.9 years, [IQR = 13.6, 16.0]) during 2017/18 - 2019/20 school years. During pre-season testing, accommodation (10.0%) and complex tandem gait (9.2%) had the largest proportion of abnormal outcomes, while smooth pursuits (10.6%) and convergence (9.5%) had the largest proportion of abnormal outcomes post-season. When assessing the effect of testing session on the relative risk of any abnormal VVE subtest, there were no significant findings (P ≥ 0.25). Additionally, there were no significant effects of testing session when adjusting for estimated head impact exposure for any VVE subtest (P ≥ 0.25). Conclusions Visio-vestibular function as measured by the VVE does not change from pre - to post-season in otherwise healthy adolescent athletes. Our findings suggest that the VVE may be stable and robust to typical neurodevelopment occurring in this dynamic age group and help inform post-injury interpretation of visio-vestibular impairments.

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.

Background Cerebello-pontine AVMs (CPAVMs) and petrous apex dural arteriovenous fistulae (DAVFs) are rare and sometimes difficult to distinguish. We report a fatal hemorrhagic complication after coil embolization of the petrosal vein draining a trigeminal AVM misdiagnosed as a DAVF. Case presentation A 73-year-old woman with a petrous apex arteriovenous shunt with dual dural and pial arterial supply presented with posterior fossa hemorrhage. The draining petrosal vein was catheterized and coiled via the superior petrosal sinus. Two episodes of contrast extravasation occurred during coiling, but the lesion was completely occluded at the end of the procedure. The patient developed a fatal posterior fossa hemorrhage in the recovery room. Microscopic pathology revealed numerous dilated vessels within the trigeminal nerve. Conclusion CPAVMs and DAVFs with pial drainage should be distinguished pre-operatively. Occlusion of a pial vein (as opposed to a sinus) in the treatment of an arteriovenous shunt carries hemorrhagic risk if a liquid embolic agent is not used to completely occlude all pathological vessels.

The formation of an intraperitoneal pseudocyst as a complication of ventriculoperitoneal shunts is well known. However, the formation of a pseudocyst at the subcutaneous extraperitoneal abdominal space is unusual and likely secondary to the migration of the peritoneal catheter. We present a 53-year-old male who had placement of a ventriculoperitoneal shunt for hydrocephalus secondary to a vestibular schwannoma. Five months later, he presented with an enormously distended abdomen. Investigations showed the peritoneal catheter in the extraperitoneal space within a large right lower quadrant abdominal wall pseudocyst. The patient was taken to the operating theatre, and the shunt was externalised at the original abdominal incision. Approximately 3 L of cerebrospinal fluid were aspirated from the distal peritoneal catheter. After negative cultures, a new peritoneal catheter was placed intraperitoneally at the contralateral lower abdominal quadrant. The contralateral quadrant was utilised to prevent fluid accumulation into the old extraperitoneal cavity.

Uterine rupture can be associated with severe maternal and neonatal morbidity and mortality. It should be considered as a differential diagnosis in all pregnant women who present with acute abdomen, haemoperitoneum and have specific risk factors, even during the first trimester. This is a case report of a 25-year-old woman who presented to emergency department with abdominal pain and vaginal bleeding at approximately 6–8 weeks gestation. She developed an acute surgical abdomen and required urgent surgical management. Despite intervention, she had massive haemorrhage, disseminate intravascular coagulation, admission to intensive care unit and prolonged hospital stay as complications. Posterior uterine wall rupture while rare, must be considered as a differential diagnosis as early intervention is crucial to prevent bad outcomes.

We present the case of a female teenager who sustained nitrous oxide burns to the medial aspect of both thighs from contact with a nitrous oxide canister being used to fill balloons. There was a delay in presentation as the injury was not initially recognised. These burns were initially assessed as being superficial partial-thickness burns but took a prolonged time to heal despite regular wound care. This was complicated by a lack of adherence to recommended treatment for much of the patient care as well as the patient testing positive for COVID-19 during their management, which prevented surgery and significantly extended time to healing. While small numbers of similar cases have been previously described this is the first reported case outside of the Netherlands and in a child. Being aware of such cases ensures early referral to specialist burn care for appropriate management to give patients the best possible outcome.

Summary Surgeons and their patients recognise that one of the major advances in surgical technique over the last 20 years has been the growth of minimal access surgery by means of laparoscopic and robotic approaches. Partnerships with industry have facilitated the development of advanced technical instruments, light sources, recording devices and optics which are almost out of date by the time they are introduced to surgical practice. However, lest we think that technological innovation is entirely a modern concept, we should remember that our predecessors were masters of their craft and able to apply new technologies to surgical practice. The history of minimal access surgery can be traced back to approximately 5000 years ago and this review aims to remind us of the achievements of historical doctors and engineers, as well as bring more modern developments to wider attention. This review will comprise a three-part series: Part I 3000BC to 1850 Early instruments for viewing body cavities Part II 1850 to 1990 Technological developments Part III 1990 to present Organisational issues and the rise of the robots

Objective To examine the relationship between enoxaparin dose adequacy, quantified with anti-Factor Xa (aFXa) levels, and 90-day symptomatic venous thromboembolism (VTE) and post-operative bleeding. Summary background data Surgical patients often develop "breakthrough" VTE events-those which occur despite receiving chemical anticoagulation. We hypothesize that surgical patients with low aFXa levels will be more likely to develop 90-day VTE, and those with high aFXa will be more likely to bleed. Methods Pooled analysis of eight clinical trials (N = 985) from a single institution over a four year period. Patients had peak steady state aFXa levels in response to a known initial enoxaparin dose, and were followed for 90 days. Survival analysis log-rank test examined associations between aFXa level category and 90-day symptomatic VTE & bleeding. Results Among 985 patients, 2.3% (n = 23) had symptomatic 90-day VTE, 4.2% (n = 41) had 90-day clinically relevant bleeding, and 2.1% (n = 21) had major bleeding. Patients with initial low aFXa were significantly more likely to have 90-day VTE than patients with adequate or high aFXa (4.2% vs. 1.3%, p = 0.007). In a stratified analysis, this relationship was significant for patients who received twice daily (6.2% vs. 1.5%, p = 0.003), but not once daily (3.0% vs. 0.7%, p = 0.10) enoxaparin. No association was seen between high aFXa and 90-day clinically relevant bleeding (4.8% vs. 2.9%, p = 0.34) or major bleeding (3.6% vs. 1.6%, p = 0.18). Conclusions This manuscript establishes inadequate enoxaparin dosing as a plausible mechanism for breakthrough VTE in surgical patients, and identifies anticoagulant dose adequacy as a novel target for process improvement measures.

OBJECTIVE: To evaluate whether pathologic complete response (pCR) exclusively defines major pathologic response to treatment with improved survival. SUMMARY BACKGROUND DATA: pCR following trimodality therapy for esophagogastric adenocarcinoma is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint. METHODS: We analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adenocarcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage treatment response (TR) in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis. RESULTS: Among 788 patients, median follow-up was 37.5 months (range, 0.4–210.6); median OS was 48.3 months (95% CI, 42.2–58.8). Absence of residual nodal disease was independently associated with improved survival (P

PURPOSE To determine the predictive value of International Classification of Diseases, 9th Revision (ICD-9) codes for identifying infantile eye diagnoses. METHODS Population-based retrospective cohort study of all residents of Olmsted County, Minnesota diagnosed at ≤1 year of age with an ocular disorder. The medical records of all infants diagnosed with any ocular disorder from January 1, 2005, through December 31, 2014, were identified. To assess ICD-9 code accuracy, the medical records of all diagnoses with ≥20 cases were individually reviewed and compared to their corresponding ICD-9 codes. Main outcome measures included positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of ICD-9 codes. RESULTS In a cohort of 5,109 infants with ≥1 eye-related ICD-9 code, 10 ocular diagnoses met study criteria. The most frequent diagnoses were conjunctivitis (N = 1,695) and congenital nasolacrimal duct obstruction (N = 1,250), while the least common was physiologic anisocoria (N = 23). The PPVs ranged from 8.3% to 88.0%, NPVs from 96.3% to 100%, sensitivity from 3.0% to 98.7%, and specificity from 72.6% to 99.9%. ICD-9 codes were most accurate at identifying physiologic anisocoria (PPV: 88.0%) and least accurate at identifying preseptal cellulitis (PPV: 8.3%). In eye specialists versus non-eye specialists, there was a significant difference in PPV of ICD-9 codes for conjunctivitis (26.8% vs. 63.9%, p

Background: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order. Objective: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation. Methods: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality. Results: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed. Conclusion: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Bruck syndrome is an autosomal recessive disease characterised by the clinical combination of both osteogenesis imperfecta and arthrogryposis multiplex congenita (AMC). It is caused due to collagen miss-folding and cross-linking defect resulting from a deletion in FKBP10 (OMIM #259450) and/or PLOD2

Study Design Retrospective cohort review. Objective To investigate the relationship between falls from height and facial injuries. Methods This is a retrospective cohort study, conducted over a 7-year period, of the medical records of all patients who presented to hospital for a maxillofacial injury following a fall from height. Fall heights were classified as low falls (1–3 m), high falls (3–10 m) and very high falls (≥10 m). Results A total of 111 patients with 218 facial bone fractures were identified (78 men, 33 women and mean age 50.3 years). High falls were the most common (n = 58, 52.3%). Multiple fractures were identified in 51 (46.0%) patients. Orbital and middle third fractures were the most prevalent. Nasal, mandible, bilateral and fractures involving more than one facial third, increased as fall height increased, as did the requirement for operative fixation. The majority of patients had an associated injury (n = 100, 90.1%) and overall mortality was 6.3%. Conclusions Falls from height are prevalent and there is a trend towards increased severity of facial injury, surgical intervention and associated morbidity as fall height increases. Falls from height are a significant public health concern and an important facet of maxillofacial trauma to recognise, as is the requirement for an interdisciplinary approach as they present to hospital.

Purpose To describe the use of glycerine in improving media clarity in cases with edematous cornea. Methods Retrospective case-series including patients with posterior segment pathologies needing surgical invention and having corneal edema. Each case was studied for the role of topical application of glycerine instead of viscoelastic agents and the course of surgery. The cases were followed up for minimum 3-months duration. Results Six cases with corneal edema having posterior segment pathology underwent surgery with intraoperative topical application of glycerine. The corneal edema was seen to clear with progression of surgery and was maintained until the end of surgery. Procedures like vitreoretinal surgery, identification of break, internal limiting membrane peeling, intraocular lens explantation, scleral indentation, DSEK graft removal, and subretinal band removal could be performed in these cases. Conclusion Intraoperative glycerine use during vitreoretinal surgeries is helpful in improving the corneal clarity and maintaining it till the end of surgery.

Objective The objective was to develop a novel scoring system that would be predictive of postoperative pulmonary complications in critically ill patients after cardiac and major vascular surgery. Methods A total of 17,433 postoperative patients after coronary artery bypass graft, valve, or thoracic aorta repair surgery admitted to the cardiovascular intensive care units at Cleveland Clinic Main Campus from 2009 to 2015. The primary outcome was the composite of postoperative pulmonary complications, including pneumonia, prolonged postoperative mechanical ventilation (>48 hours), or reintubation occurring during the hospital stay. Elastic net logistic regression was used on the training subset to build a prediction model that included perioperative predictors. Five-fold cross-validation was used to select an appropriate subset of the predictors. The predictive efficacy was assessed with calibration and discrimination statistics. Post hoc, of 13,353 adult patients, we tested the clinical usefulness of our risk prediction model on 12,956 patients who underwent surgery from 2015 to 2019. Results Postoperative pulmonary complications were observed in 1669 patients (9.6%). A prediction model that included baseline and demographic risk factors along with perioperative predictors had a C-statistic of 0.87 (95% confidence interval, 0.86-0.88), with a corrected Brier score of 0.06. Our prediction model maintains satisfactory discrimination (C-statistics of 0.87) and calibration (Brier score of 0.07) abilities when evaluated on an independent dataset of 12,843 recent adult patients who underwent cardiovascular surgery. Conclusions A novel prediction nomogram accurately predicted postoperative pulmonary complications after major cardiac and vascular surgery. Intensivists may use these predictors to allow for proactive and preventative interventions in this patient population.

This study examined the prospective associations among the trajectories of maternal depressive symptoms, maternal sensitivity, and child executive function (EF) across early and middle childhood, and tested the mediating role of maternal sensitivity in the links between change in maternal depressive symptoms and the growth of child EF. Participants included 1,364 children and mothers from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (NICHD SECCYD). We found that maternal depressive symptoms (from 6 months to Grade 5) and sensitivity (from 36 months to Grade 5) decreased, whereas child EF (planning skills; from Grade 1 to 5) increased over time. We also found several direct associations: (a) lower maternal depressive symptoms at 36 months predicted higher sensitivity at 54 months; (b) higher sensitivity at 54 months and a faster decrease in sensitivity from 36 months to Grade 5 predicted higher child EF in Grade 1; and (c) higher sensitivity at 54 months predicted greater growth of EF from Grade 1 to 5. In addition, two mediation effects were found as follows: Lower levels of maternal depressive symptoms at 36 months predicted both higher levels of child EF in Grade 1 and greater growth of EF from Grade 1 to 5 through higher levels of maternal sensitivity at 54 months. The results suggest that early maternal depressive symptoms may have long-term effects on the growth of EF, especially planning skills, during middle childhood, and that one important pathway that maternal depressive symptoms affect child EF outcomes through maternal sensitivity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Beta blockers, mainly propranalol, are usually administered to control heart rate in patients with thyrotoxicosis, especially when congestive heart failure presents. However, when thyrotoxicosis is not controlled, heart rate may be difficult to control even with maximal doses of propranolol. This presentation alerts physicians to the possibility of using ivabradine, a selective inhibitor of the sinoatrial pacemaker, for the control of heart rate. Case presentation: We present a 37-year-old woman with thyrotoxicosis and congestive heart failure whose heart rate was not controlled with a maximal dose of beta blockers during a thyroid storm. The addition of ivabradine, a selective inhibitor of the sinoatrial pacemaker, controlled her heart rate within 48 hours. Conclusion: Ivabradine should be considered in patients with thyrotoxicosis, including those with heart failure, in whom beta blockers are insufficient to control heart rate