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To assess the prevalence of abortion among population groups and changes in rates between 2008 and 2014.We used secondary data from the Abortion Patient Survey, the American Community Survey, and the National Survey of Family Growth to estimate abortion rates. We used information from the Abortion Patient Survey to estimate the lifetime incidence of abortion.Between 2008 and 2014, the abortion rate declined 25%, from 19.4 to 14.6 per 1000 women aged 15 to 44 years. The abortion rate for adolescents aged 15 to 19 years declined 46%, the largest of any group. Abortion rates declined for all racial and ethnic groups but were larger for non-White women than for non-Hispanic White women. Although the abortion rate decreased 26% for women with incomes less than 100% of the federal poverty level, this population had the highest abortion rate of all the groups examined: 36.6. If the 2014 age-specific abortion rates prevail, 24% of women aged 15 to 44 years in that year will have an abortion by age 45 years.The decline in abortion was not uniform across all population groups.

The regenerative capabilities of the liver represent a paradigm for understanding tissue repair in solid organs. Regeneration after partial hepatectomy in rodent models is well understood, while regeneration in the context of clinically relevant chronic injuries is less studied. Given the growing incidence of fatty liver disease, cirrhosis, and liver cancer, interest in liver regeneration is increasing. Here, we will review the principles, genetics, and cell biology underlying liver regeneration, as well as new approaches being used to study heterogeneity in liver tissue maintenance and repair.

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.

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

OBJECTIVES: Following the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and the subsequent global spread of the 2019 novel coronavirus disease (COVID-19), health systems and the populations who use them have faced unprecedented challenges. We aimed to measure the impact of COVID-19 on the uptake of hospital-based care at a national level. DESIGN: The study period (weeks ending 5 January to 28 June 2020) encompassed the pandemic announcement by the World Health Organization and the initiation of the UK lockdown. We undertook an interrupted time-series analysis to evaluate the impact of these events on hospital services at a national level and across demographics, clinical specialties and National Health Service Health Boards. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from National Health Service Scotland. MAIN OUTCOME MEASURES: Accident and emergency (A&E) attendances, and emergency and planned hospital admissions measured using the relative change of weekly counts in 2020 to the averaged counts for equivalent weeks in 2018 and 2019. RESULTS: Before the pandemic announcement, the uptake of hospital care was largely consistent with historical levels. This was followed by sharp drops in all outcomes until UK lockdown, where activity began to steadily increase. This time-period saw an average reduction of −40.7% (95% confidence interval [CI]: −47.7 to −33.7) in A&E attendances, −25.8% (95% CI: −31.1 to −20.4) in emergency hospital admissions and −60.9% (95% CI: −66.1 to −55.7) in planned hospital admissions, in comparison to the 2018–2019 averages. All subgroup trends were broadly consistent within outcomes, but with notable variations across age groups, specialties and geography. CONCLUSIONS: COVID-19 has had a profoundly disruptive impact on hospital-based care across National Health Service Scotland. This has likely led to an adverse effect on non-COVID-19-related illnesses, increasing the possibility of potentially avoidable morbidity and mortality. Further research is required to elucidate these impacts.

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.

Depression and related mood disorders constitute an enormous burden on health, quality of life, and the global economy, and women have roughly twice the lifetime risk of men for experiencing depression. Here, we review sex differences in human brain physiology that may be connected to the increased susceptibility of women to major depressive disorder (MDD). Moreover, we summarize decades of preclinical research using animal models for the study of mood dysfunction that uncover some of the potential molecular, cellular, and circuit-level mechanisms that may underlie sex differences and disease etiology. We place particular emphasis on a series of recent studies demonstrating the central contribution of the circuit projecting from ventral hippocampus to nucleus accumbens and how inherent sex differences in the excitability of this circuit may predict and drive depression-related behaviors. The findings covered in this review underscore the continued need for studies using preclinical models and circuit-specific strategies for uncovering molecular and physiological mechanisms that could lead to potential sex-specific diagnosis, prognosis, prevention, and/or treatments for MDD and other mood disorders.

This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The insights provided by the growing use of next-generation sequencing (NGS) in lung cancer will be discussed, and interrelated concepts such as intertumor heterogeneity, intratumor heterogeneity, tumor mutational burden, and the advent of liquid biopsy will be explored. Moreover, this work describes how the evolving field of molecular pathology refines the understanding of different histologic phenotypes of non-small-cell lung cancer (NSCLC) and the underlying biology of small-cell lung cancer. This review will provide an appreciation for how ongoing scientific findings and technologic advances in molecular pathology are crucial for development of biomarkers, therapeutic agents, clinical trials, and ultimately improved patient care.

• 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.

• The placenta is the first organ to form in mammals and is required for establishment of a maternal–fetal vascular interface capable of supplying the bioenergetic needs of the developing conceptus. • Multiple placental cell types engage in highly varied functions, from attachment, invasion, and vascular remodeling to cell fusion, hormone production, and nutrient transport. • Multiple mechanisms allow transport of waste and nutrients across the placenta, including diffusion, transporter protein-mediated (facilitated diffusion and active transporters), and receptor-mediated mechanisms. • The placenta is not an inert transport interface. It consumes 40%–60% of the oxygen and glucose delivered to the uterus at term. Thus conditions that alter placental metabolism can indirectly affect nutrient transport to the fetus. • Maternal and fetal health alter placental function, which in turn influences fetal adaptations and contributes to in utero fetal programming. • Abnormal placentation and placental infections can lead to preeclampsia (PE), fetal growth retardation, or preterm birth, which can have lifelong bearing on health. • In the United States, iatrogenic delivery is responsible for almost half the births that occur between 28 and 37 weeks of gestation, primarily caused by placental pathologies such as PE or intrauterine growth restriction. • Efforts to standardize placental examination after delivery are in progress so that connections between specific placental problems and poor outcomes can be better defined. In parallel, new advanced imaging techniques and biomarkers for placental function are being developed.

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.

This review identifies the three-dimensional knee loads that have the highest risk of injuring the anterior cruciate ligament (ACL) in the athlete. It is the combination of the muscular resistance to a large knee flexion moment, an external reaction force generating knee compression, an internal tibial torque, and a knee abduction moment during a single-leg athletic manoeuvre such as landing from a jump, abruptly changing direction, or rapidly decelerating that results in the greatest ACL loads. While there is consensus that an anterior tibial shear force is the primary ACL loading mechanism, controversy exists regarding the secondary order of importance of transverse-plane and frontal-plane loading in ACL injury scenarios. Large knee compression forces combined with a posteriorly and inferiorly sloped tibial plateau, especially the lateral plateau-an important ACL injury risk factor-causes anterior tibial translation and internal tibial rotation, which increases ACL loading. Furthermore, while the ACL can fail under a single supramaximal loading cycle, recent evidence shows that it can also fail following repeated submaximal loading cycles due to microdamage accumulating in the ligament with each cycle. This challenges the existing dogma that non-contact ACL injuries are predominantly due to a single manoeuvre that catastrophically overloads the ACL.

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.

A new section on the approach to diagnostic histological interpretation, is the overture to this chapter on inherited and developmental disorders. This initial section is split chronologically into the early neonatal and infantile period and later childhood and adulthood; with the intention of reflecting clinical practice as closely and succinctly as possible. Disorders of the biliary tree, bile formation and secretion, and hepatocyte metabolism are the core of this chapter, a merger of chapters 3 and 4 of the previous edition. Considerations on the pathogenetic and/or clinical overlap between developmental, genetic and metabolic disorders were the rationale behind this change. The complexity of hepatocyte metabolism is reflected into the miriad of related pathological conditions. Recent technological advances, particularly in genomics in the last five years, have resulted in a plethora of new entities and changes in terminology, challenging the authors to balance detail and application to clinical practice. Tables and figures from previous editions have been largely kept due to their quality and contemporary relevance, whilst new ones have been added to accommodate new advances (e.g. classification of mitochondrial disorders), a compromise to bridge between the two editions for the accustomed reader. Liver involvement in immunodeficiency and miscellaneous disorders precede the final section on anatomical anomalies. Vascular anomalies are now included in the chapters on vascular disorders.

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).

In the general population, the construct of race is associated with disparities in cognitive aging. There are notable racial group disparities and inequities among people living with schizophrenia (PLWSz). Despite the salience of the construct of race in schizophrenia, there remains a knowledge gap about racial disparities in cognitive impairment among older adults in this vulnerable population. Our study uses mediation analysis to examine racial disparities in cognitive impairment among older adults with schizophrenia.We assess global cognition in PLWSz over age 55 with the Measurement and Treatment Research to Improve Cognition in Schizophrenia cognitive test battery in our "all-comer" sample (There was a Black/non-Black group racial disparity in global cognitive score (-2.8, 95% CI: -4.4, -1.3) after adjusting for confounding and interaction. This disparity was significantly mediated by years of education.There are notable racial disparities in cognitive impairment among older adults with schizophrenia; however, differences in cognitive scores between racial groups are mediated by level of education.Social determinants of health, particularly educational attainment, are important risk factors for cognitive impairment in PLWSz and should be considered by clinicians. Early screening and assessment of cognitive symptoms is essential to addressing health disparities/inequalities among older adults living with schizophrenia.Controlled Direct EffectsHIV: Human Immunodeficiency VirusMATRICS: Measurement and Treatment Research to Improve Cognition in SchizophreniaMCCB: MATRICS Consensus Cognitive BatteryMTE: Marginal Total EffectsNDE: Natural Direct EffectsPANSS: Positive and Negative Symptom ScalePLWSz: People with schizophrenia.

• Owing to their cutaneous, immunologic, and renal immaturity, newborns (especially premature neonates) are at increased risk of infection. • As a group of potentially life-threatening but often treatable diseases, infections must always be considered in a newborn with skin lesions. • Prompt diagnosis and initiation of therapy are crucial to prevent devastating long-term sequelae, particularly in instances of disseminated disease. • Staphylococcus aureus, Streptococcus species, Candida albicans, and herpes simplex virus are the most common causes of skin infections in the neonate.

• 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.

Occurrence of biogenic amines in fresh fish and fishery products constitute a significant safety concern. Ingestion of histamine is identified as the causative agent of several food poisoning incidences on an annual basis. In addition, cadaverine, putrescine and tyramine have been recognized as potentiators of histamine poisoning. Accumulation of biogenic amines in fresh fish and fishery products has been mainly attributed to growth of bacteria possessing amino acid decarboxylase activity, which is facilitated by lack of hygienic conditions and strict temperature control during their storage. To this end, the effectiveness of traditional and modern approaches to control biogenic amine accumulation has been in the epicenter of intensive study. The aim of the present review article is to update and integrate current knowledge regarding the biogenic amine content of fresh fish and fishery products as well as the capacity of traditional and emerging control strategies.

The average values of the seasonal flesh biochemical composition (%) of the pearl oyster Pinctada imbricata radiata originated form 2 sampling sites, the gulfs of Evoikos (E) and Saronikos (S) in the Western Aegean Sea, showed that is rich in proteins (64.00 ± 1.86 -(E), 64.67 ± 2.95-(S)) with low fat content (10.96 ± 1.04-(E), 11.86 ± 1.13-(S)) and carbohydrates (13.29 ± 2.48- (E), 9.94 ± 4.32 (S)). The condition index ranged from 26.16% ± 5.04 in the autumn in (E), to 44.73% ± 7.50 in the summer in (S). The meat yield varied from 20.49% ± 3.20% in the summer in (E) to 30.73% ± 3.47% in the summer in (S). Both results demonstrate the high nutritional profile of the pearl oyster, supporting its suitability as a potential new Mediterranean seafood source for human consumption.

Objective: Relational and emotional vulnerability represent essential problems among patients with personality disorder (PD). Group psychotherapy is a central component of evidence-based PD treatments. Generally, patient and therapist interrelationships predict improvement in therapy. However, although treatment of patients with PD is a more complex process, group processes are poorly elaborated in PD research. Documentation of the psychometric quality of group process measures in PD samples is an important precursor of such research. The Group Questionnaire—GQ is based on concepts of group cohesion and climate, empathy, and alliance and aims to capture the quality of member–member, member–group, and member–leader relationships in group therapy. A three latent factor structure (positive bond, positive work, and negative relationship) has generally been supported. This study aimed to perform a psychometric analysis of GQ administered in a clinical population of patients with PD. Method: The study included 369 patients with PDs attending group psychotherapy in 14 outpatient treatment units on a specialist mental health service level within the Norwegian Network of Personality Disorders in the period 2017–2020. Psychometric analyses included three latent factors and eight subfacets. Results: The three latent factors, positive bond, positive work, and negative relationship, were replicated. Psychometric integrity of the tripartite relationship structure—member–member, member–group, and member–leader, with eight subfacets, was supported. Conclusion: The GQ with three latent factors and eight subfacets can be recommended for future research and clinical practice in patient populations with PD.

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

Findley first proposed the presence of age-related dysfunction of the hypothalamic-neurohypophyseal-renal axis more than 60 years ago. More sophisticated studies have since corroborated his findings. As a result, it is now clear that multiple abnormalities in water homeostasis occur commonly with aging, and that the elderly are uniquely susceptible to disorders of body volume and osmolality. This article summarizes the distinct points along the hypothalamic-neurohypophyseal-renal axis where these changes have been characterized, as well as the clinical significance of these changes, with special attention to effects on cognition, gait instability, osteoporosis, fractures, and morbidity and mortality.

Background Neutrophilic dermatosis of the dorsal hands is an uncommon localised variant of Sweet syndrome first described in 1995. It is characterised by tender erythematous plaques, pustules and bullae on the dorsa of the hands. Literature Review A total of 123 cases of NDDH are included in this review. The mean patient age was 62.1 years and there was a slight female preponderance. 78.0% of cases had reported bilateral involvement and other sites were affected in almost a third of cases. Underlying disease was found in around 40% of patients, with the most common associations being haematological disorders (gammopathies, myelodysplasias or malignancies), recent infection, solid organ tumours and inflammatory bowel disease. Systemic and/or topical corticosteroids were employed in the treatment of 88.1% of cases while dapsone, colchicine and tetracyclines were the commonest steroid-sparing agents used. Improvement was often rapid and complete resolution the norm. Conclusions Whilst being uncommon, NDDH is frequently misdiagnosed and thus, its exact prevalence is probably underestimated. This may have significant implications including treatment delays or incorrect management. Moreover, recognition of NDDH is important since a correct diagnosis should trigger a search for underlying diseases and proper treatment with corticosteroids and/or steroid-sparing agents which is almost invariably curative.

PurposeStudies on the association between peripheral neuropathy (PN) and patient-reported outcomes have mostly overlooked sleep quality. Therefore, we aimed to assess the association between PN and sleep quality in a population-based sample of colorectal cancer (CRC) patients up two years after diagnosis. MethodsAll newly diagnosed CRC patients from four Dutch hospitals were eligible for participation. Patients (N=340) completed questionnaires about PN (EORTC QLQ-CIPN20) and sleep (PSQI) before initial treatment (baseline) and one and two years after diagnosis. ResultsPatients who developed sensory PN (n=76) or motor PN (n=79) after treatment more often reported poor sleeping scores (PSQI>5) compared with those who did not develop SPN or MPN at 1-year (SPN: 38% vs. 261%, MPN: 37% vs. 14%) and 2-year follow-up (SPN: 38 vs. 23%, MPN: 37% vs. 18%) (all pConclusionsBoth SPN and MPN were significantly associated with the course of sleep quality among CRC patients up to two years after diagnosis. Clinicians should be encouraged to discuss sleep quality with their patients who either report PN or are at risk of developing PN. Implications for survivors: Improving sleep quality among survivors with PN is important, either by reducing PN symptoms, or directly targeting sleep

Background Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD. Objective To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs). Methods Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib. Results Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities. Limitations This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. Conclusions With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is an X-linked disease caused by activating mutations in the arginine vasopressin (AVP) receptor-2 (AVPR2) gene. Affected patients excrete concentrated urine despite very low levels of AVP, and consequently develop euvolemic hyponatremia. Due to its low frequency, patients may be misdiagnosed and treated incorrectly. We report two related male infants with NSIAD that was initially confused with hyporeninemic hypoaldosteronism (HH). First, a 2-month-old male presented with hyponatremia, low plasma osmolality, relatively high urine osmolality, and low plasma renin-aldosterone levels. These clinical and laboratory findings were compatible with syndrome of inappropriate antidiuretic hormone secretion without apparent cause. Consequently,fludrocortisone was initiated with a presumptive diagnosis of HH While correction of hyponatremia, fludrocortisone treatment led to hypertension and discontinued in a short time. The second patient at age of 1 year was admitted with a history of oligohydramnios, four times hospitalizations due to hyponatremia since birth, and a diagnosis of epilepsy. Similarly, the second infant had clinical and laboratory findings compatible with syndrome of inappropriate antidiuretic hormone secretion with no apparent cause. Fluid restriction normalized his serum sodium despite plasma AVP level was undetectable. In both infants, AVPR2 gene analysis revealed a known mutation (c.409C>T; p.R137C) and confirmed the diagnosis of NSIAD. In conclusion, NSIAD should be considered in all patients with unexplained euvolemic hyponatremia despite high urine osmolality. In case of unawareness from NSIAD, plasma renin-aldosterone profile can be confused with HH, especially in the infants. 34645113

Variants of the melanocortin-4 receptor (MC4R) gene are the most common cause of monogenic obesity. In this situation; while obesity cannot be controlled with diet and exercise, it was shown that Glucagon-like-peptide-1 receptor agonists (GLP-1 RA) provide weight loss in short term. In this paper, we present our experience with Liraglutide treatment in an adolescent patient carrying MC4R gene variant. A female patient had admitted first at the age of 12.5 years with a complaint of progressive weight gain. She had a marked excess of appetite since infancy. In the physical examination of the pubertal female patient with a body mass index (BMI) of 36.1kg/m2 (3.48 SDS), there was no pathological finding except diffuse acanthosis nigricans. Laboratory examinations revealed only insulin resistance. Weight loss couldn't be achieved with lifestyle changes, metformin and orlistat treatments In genetic examination, a sporadic heterozygous c.206T>G(p.I69R) variant (reported previously) was found in the MC4R gene. GLP-1 RA Liraglutide treatment was initiated and a loss of 19.2% reduction was achieved in the patient's body weight and BMI at the end of 32 weeks. However, the patient, whose treatment compliance was disrupted due to significant gastrointestinal complaints, returned to her former weight within a few months after treatment was stopped. In our case carrying a pathogenic variant in the MC4R gene, decrease of appetite and weight loss were achieved with Liraglutide treatment, but this situation could not be maintained. In such cases, there is a need for effective and tolerable treatment options.

Prolyl endopeptidase-like (PREPL) deficiency (MIM#616224) is a rare congenital disorder characterised by neonatal hypotonia and feeding difficulties, growth hormone (GH) deficiency and hypergonadotropic hypogonadism. This syndrome is an autosomal recessive disease resulting from mutations in the PREPL gene (MIM#609557). Herein we report a 7-year-old female patient with biallelic mutations in PREPL (c.1528C>T in one allele and a whole gene deletion in the other) with early growth impairment in infancy. Growth hormone deficiency was confirmed at 20 months of life. Recombinant growth hormone treatment was introduced with a good response. Her clinical features were similar to those of previously reported cases. The description of new patients with PREPL deficiency syndrome is essential to better delineate the phenotypic and genotypic spectrum of the disease.

Proses dehidrasi merupakan salah satu proses yang sering dijumpai pada pabrik pengolahan gas alam. TEG (triethylene glycol) merupakan senyawa Glycol yang biasa digunakan pada proses dehidrasi gas alam. TEG dimanfaatkan sebagai absorben pada absorpsi air yang masih terkandung dalam gas alam yang bisa menyebabkan hydrate dan korosi. Proses absorpsi ini dilakukan di TEG contactor, TEG yang sudah digunakan akan dilakukan regenerasi, jika sudah di regenerasi maka TEG akan digunakan kembali. Tujuan dari penelitian ini yaitu melakukan proses estimasi temperatur yang sesuai untuk proses absorpsi unit regenerasi TEG, karena banyak TEG loss pada proses ini. TEG loss terjadi di TEG regenerator dan biasanya disebabkan oleh temperatur kondensor refluks yang kurang tepat sehingga menyebabkan TEG teruapkan keluar ke atmosfer bersama uap air. Kehilangan TEG adalah masalah bagi operasi yang penting dalam sistem dehidrasi. Langkah yang digunakan untuk mengurangi TEG loss adalah dengan melakukan estimasi temperatur dari condensor refluks dibuat menjadi 100°C dengan cara mengubah temperatur reboiler dari 190°C menjadi 197,3°C.

PURPOSE Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. PATIENTS AND METHODS This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia ( P ≤ .001); febrile neutropenia ( P = .002); and alopecia ( P < .001) were significantly lower, whereas grade 3 or 4 nausea ( P = .004) was more common. CONCLUSION In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Background Postpartum depression (PPD) has been associated with adverse health outcomes including maternal suicide. Mode of delivery has been suggested to be a risk factor for PPD, but no large cohort study has examined the association between mode of delivery and PPD. We aimed to examine the association between mode of delivery and risks of PPD at 1 and 6 months after childbirth. Methods In a nationwide study of 89,954 mothers with a live singleton birth, we examined the association between mode of delivery and risks of PPD. PPD was measured by the Edinburgh Postnatal Depression Scale (≥13) at 1 and 6 months after childbirth. Odds ratios (ORs) with 95% confidence intervals (CIs) of PPD were calculated using multivariable logistic regression analyses after adjustment of antenatal physical, socioeconomic, and mental factors. Results Among 89,954 women, 3.7% and 2.8% had PPD at 1 and 6 months after childbirth, respectively. Compared with unassisted vaginal delivery, cesarean section (CS) was marginally associated with PPD at 1 month, but not at 6 months; adjusted ORs were 1.10 (95% CI, 1.00-1.21) and 1.01 (95% CI, 0.90-1.13), respectively. The association with PPD at 1 month was evident in women with antenatal psychological distress: adjusted OR was 1.15 (95% CI, 1.03-1.28). The observed associations were attenuated after adjusting for infant feeding method. Conclusions Women who had antenatal psychological distress and underwent CS delivery may be regarded as a target for monitoring PPD.

BackgroundBreast cancer is the most common malignancy among Iranian women. In recent years, the study of dysfunction in the expression of cell-cell junction genes and the related proteins in the malignant process has been at the center of attention. MethodsIn this study, 50 patients were selected who had both cancerous tissue and adjacent healthy tissue. The expression of the desmoglein 2 gene was evaluated. Healthy and cancerous tissue were compared using routine hematoxylin and eosin staining. The total protein was also compared between these two groups. The ultrastructural examination was performed.ResultsThe real-time polymerase chain reaction results showed a decrease in the expression of the desmoglein 2 gene in all tumor samples compared to the healthy samples (p-value ConclusionOverall, the findings showed that the association between desmoglein 2 gene expression and alterations in cellular connections leads to impaired cellular connections, which is an important risk factor for breast cancer. This result proposed the understudy gene as a new biomarker in the development of breast cancer.

Responding to a healthcare crisis such as COVID-19 requires a practiced, nimble incident command structure. Our medical center is in one of the areas in the US that was hardest hit by the initial wave. Effective leadership of incident command was critical in our response.

Introduction GOLD 2017 report proposed that the combined COPD assessment should be done according only to symptom burden and exacerbation history in the previous year. Objective This study aims to investigate the change in the COPD groups after the GOLD 2017 revision and also to discuss the evaluation of group C and D as a single group after the GOLD 2019 report. Method The study was designed as a cross-sectional. 251 stable COPD patients admitted to our out-patient clinic; aged ≥40 years, at least one-year diagnosis of COPD and ≥10 pack-year smoking history were consecutively recruited for the study. Results In GOLD 2017, a significant difference was found between the distribution of all groups compared to GOLD 2011 (P = 0,001). 31 patients included in group C were reclassified into group A and 37 patients in group D were reclassified into group B. The FEV1 values of group A and B patients were significantly low and group C and D patients had had exacerbations in more frequently the previous year in GOLD 2017 compared to GOLD 2011. Conclusion After the GOLD 2017 revision, the rate of group C patients decreased even more compared to GOLD 2011 and the group C and D may be considered as a single group in terms of the treatment recommendations with the GOLD 2019 revision. We think that future prospective studies are needed to support this suggestion.

INTRODUCTION Advances in the treatment of myasthenia gravis (MG) have improved quality of life and prognosis for the majority of patients. However, 10%-20% of patients present refractory MG, with frequent relapses and significant functional limitations. PATIENTS AND METHODS Patients with refractory MG were selected from a cohort of patients diagnosed with MG between January 2008 and June 2019. Refractory MG was defined as lack of response to treatment with prednisone and at least 2 immunosuppressants, inability to withdraw treatment without relapse in the last 12 months, or intolerance to treatment with severe adverse reactions. RESULTS We identified 84 patients with MG, 11 of whom (13%) met criteria for refractory MG. Mean (standard deviation) age was 47 (18) years; 64% of patients with refractory MG had early-onset generalised myasthenia (as compared to 22% in the group of patients with MG; P