Prevalence, characteristics and risk factors of frequently readmitted patients to an internal medicine service.

BACKGROUND: Unplanned hospital readmissions (HRA), which have been used as key performance index of healthcare quality, are becoming more prevalent. They are associated with substantial financial burden to hospital systems and considerable impacts on patients' physical and mental health. Patients with frequent readmissions are not well studied. AIMS: To determine the prevalence, characteristics and risk factors associated with frequent readmissions (FRA) to an internal medicine service at a tertiary public hospital. METHOD: A retrospective observational study was conducted at an internal medicine service in a tertiary teaching hospital between 1 January 2010 and 30 June 2016. FRA was defined as four or more readmissions within 12 months of discharge from the index admission (IA). Demographic and clinical characteristics and potential risk factors were evaluated. RESULTS: A total of 50 515 patients was included; 1657 (3.3%) had FRA and were associated with nearly 2.5 times higher in 12-month mortality rates. They were older, had higher rates of indigenous Australians (3.2%), more disadvantaged status (index of relative socio-economic disadvantage decile of 5.3) and more comorbidities (mean Charlson comorbidity index 1.4) in comparison, to infrequent readmission group. The mean length of hospital stay during the IA was 6 days for FRA group (21.4% staying more than 7 days) with higher incidence of discharge against medical advice (2.0% higher). Intensive care unit admission rate was 6.6% for FRA group compared with 3.9% for infrequent readmission group. Multivariate analysis showed mental disease and disorders, neoplastic, alcohol/drug use and alcohol/drug-induced organic mental disorders are associated with FRA. CONCLUSION: The risk factors associated with FRA were older age, indigenous status, being socially disadvantaged, having higher comorbidities and discharging against medical advice. Conditions that lead to FRA were mental disorders, alcohol/drug use and alcohol/drug-induced organic mental disorders and neoplastic disorders.

Who Should be Following the Trans-Female Patient Pre and Post Vaginoplasty? An Argument for the Pediatric Gynaecologist.

Increasing numbers of transgender patients are opting for gender-affirming care. Since pediatric and adolescent gynaecology (PAG) providers perform the majority of vaginoplasty procedures for developmental anomalies of the female reproductive tract (such as vaginal agenesis), this commentary supports the position that PAG providers should be involved in the pre- and postoperative care of trans women.

Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control.

Virus-specific CD8+ T cells probably mediate control over HIV replication in rare individuals, termed long-term nonprogressors (LTNPs) or elite controllers. Despite extensive investigation, the mechanisms responsible for this control remain incompletely understood. We observed that HIV-specific CD8+ T cells of LTNPs persisted at higher frequencies than those of treated progressors with equally low amounts of HIV. Measured on a per-cell basis, HIV-specific CD8+ T cells of LTNPs efficiently eliminated primary autologous HIV-infected CD4+ T cells. This function required lytic granule loading of effectors and delivery of granzyme B to target cells. Defective cytotoxicity of progressor effectors could be restored after treatment with phorbol ester and calcium ionophore. These results establish an effector function and mechanism that clearly segregate with immunologic control of HIV. They also demonstrate that lytic granule contents of memory cells are a critical determinant of cytotoxicity that must be induced for maximal per-cell killing capacity.

Adolescent pregnancy outcomes in the province of Ontario: a cohort study.

OBJECTIVE: Few Canadian studies have examined the association between adolescent pregnancy and adverse pregnancy outcomes. The objective of this cohort study was to characterize the association between adolescent pregnancy and specific adverse maternal, obstetrical, and neonatal outcomes, as well as maternal health behaviours. METHODS: We conducted a retrospective population-based cohort study of all singleton births in Ontario between January 2006 and December 2010, using the Better Outcomes Registry and Network database. Outcomes for pregnant women < 20 years of age (adolescent) were compared with those of women 20 to 35 years old (adult). RESULTS: This study included 551 079 singleton birth records, 23 992 (4.35%) of which derived from adolescent pregnancies. Adolescents had a higher rate of smoking and substance use than adult women and were within the lowest education and family income quintiles. Adolescents had a significantly lower risk of gestational hypertension (adjusted relative risk [aRR] 0.73) and gestational diabetes (aRR 0.34), placental abruption (aRR 0.80), and placenta previa (aRR 0.36), but their risk of preterm premature rupture of membranes was significantly higher (RR 1.16). Adolescents had a significantly higher proportion of spontaneous vaginal delivery (aRR 1.76), significantly lower rates of use of epidural analgesia (aRR 0.93), of Caesarean section (aRR 0.57), and of assisted vaginal delivery (aRR 0.76), but a significantly higher risk of emergency CS (aRR 1.31). Neonates with an adolescent mother had significantly higher risks of admission to NICU (aRR 1.08) and very preterm birth (aRR 1.16). There was no significant difference between the two groups in rates of small for gestational age babies, low birth weight, preterm birth, and fetal death. Adolescents had significantly lower rates of prenatal class attendance, prenatal visits in the first trimester, and breastfeeding. CONCLUSION: This large Canadian cohort study confirms that, compared with adults, adolescents have improved outcomes such as lower rates of gestational hypertension, gestational diabetes, antepartum hemorrhage, and operative deliveries. However, adolescents also have higher sociodemographic risk factors and seek prenatal care later than adults. These risk factors in combination with young age, lead to other important maternal, obstetrical, and neonatal adverse outcomes. These findings highlight the importance of multidisciplinary prenatal management in the adolescent population to address their high-risk needs, to ensure healthy pregnancies, and to reduce adverse perinatal outcomes.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) in pregnancy: a case series of nine patients and review of literature.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by myocardial necrosis and fibrofatty substitution of the myocardium, predominantly of the right ventricle. The evaluation of risk associated with gestation and delivery in patients with ARVC is difficult due to the small number of already reported cases. We present our experience of patients with ARVC who completed a pregnancy and delivery. METHODS: A case series of nine women in Calgary, Canada, from 2013 to 2018, who were diagnosed with ARVC before or during pregnancy. Patients were identified using our Cardiac-Obstetrics database, and information was collected through electronic charts and patient recollection. RESULTS: All pregnancies reported were singleton with an average maternal age of 31 years. Six patients had a related genetic mutation. Beta blockers were being used by eight, and five had an implantable cardioverter-defibrillator (ICD) prior to the pregnancy. None of the patients developed heart failure during pregnancy, but one had a complicated antepartum and postpartum course. All pregnancies delivered at term with eight receiving neuroaxial analgesia. Five patients delivered vaginally. Those without an ICD had continuous cardiac monitoring intrapartum. The incidence of small for gestational age (33%) was higher than the general population. All of the patients breastfed the newborns. CONCLUSIONS: Pregnancies in these patients with ARVC were generally well tolerated. Given the rarity of the disease and absence of any clinical guidelines, multidisciplinary care is essential in the management of these patients.

Pregnancy and Placenta Increta in a Noncommunicating Uterine Horn.

BACKGROUND: We present a rare case of pregnancy and invasive placentation in a unruptured, noncommunicating rudimentary uterine horn at 20 weeks' gestation. CASE: The patient was followed with ultrasound throughout early pregnancy and initial imaging for dating purposes showed a pregnancy within a communicating right horn of the uterus. At the 18-week anatomy ultrasound, the pregnancy was discovered to be within the noncommunicating, rudimentary left horn of the uterus. This was confirmed using pelvic magnetic resonance imaging. The patient opted for surgical management and subsequently underwent laparotomy and removal of the noncommunicating uterine horn and pregnancy. Placental tissue was adherent to the level of the serosa during surgery and pathologic diagnosis was significant for a placenta increta. SUMMARY AND CONCLUSION: The patient recovered well from surgery and subsequently went on to have a successful term pregnancy delivered via cesarean section for breech in the right horn 15 months later.

Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy.

Identifying the functions of human immunodeficiency virus (HIV)-specific CD8+ T cells that are not merely modulated by the level of virus but clearly distinguish patients with immune control from those without such control is of paramount importance. Features of the HIV-specific CD8+ T-cell response in antiretroviral-treated patients (designated Rx <50) and untreated patients (long-term nonprogressors [LTNP]) matched for very low HIV RNA levels were comprehensively examined. The proliferative capacity of HIV-specific CD8+ T cells was not restored in Rx <50 to the level observed in LTNP, even though HIV-specific CD4+ T-cell proliferation in the two patient groups was comparable. This diminished HIV-specific CD8+ T-cell proliferation in Rx <50 was primarily due to a smaller fraction of antigen-specific cells recruited to divide and not to the numbers of divisions that proliferating cells had undergone. Exogenous interleukin-2 (IL-2) induced proliferating cells to divide further but did not rescue the majority of antigen-specific cells with defective proliferation. In addition, differences in HIV-specific CD8+ T-cell proliferation could not be attributed to differences in cellular subsets bearing a memory phenotype, IL-2 production, or PD-1 expression. Although polyfunctionality of HIV-specific CD8+ T cells in Rx <50 was not restored to the levels observed in LTNP despite prolonged suppression of HIV RNA levels, per-cell cytotoxic capacity was the functional feature that most clearly distinguished the cells of LTNP from those of Rx <50. Taken together, these data suggest that there are selective qualitative abnormalities within the HIV-specific CD8+ T-cell compartment that persist under conditions of low levels of antigen.

Comparisons of CD8+ T cells specific for human immunodeficiency virus, hepatitis C virus, and cytomegalovirus reveal differences in frequency, immunodominance, phenotype, and interleukin-2 responsiveness.

To better understand the components of an effective immune response to human immunodeficiency virus (HIV), the CD8(+) T-cell responses to HIV, hepatitis C virus (HCV), and cytomegalovirus (CMV) were compared with regard to frequency, immunodominance, phenotype, and interleukin-2 (IL-2) responsiveness. Responses were examined in rare patients exhibiting durable immune-mediated control over HIV, termed long-term nonprogressors (LTNP) or elite controllers, and patients with progressive HIV infection (progressors). The magnitude of the virus-specific CD8(+) T-cell response targeting HIV, CMV, and HCV was not significantly different between LTNP and progressors, even though their capacity to proliferate to HIV antigens was preserved only in LTNP. In contrast to HIV-specific CD8(+) T-cell responses of LTNP, HLA B5701-restricted responses within CMV pp65 were rare and did not dominate the total CMV-specific response. Virus-specific CD8(+) T cells were predominantly CD27(+)45RO(+) for HIV and CD27(-)45RA(+) for CMV; however, these phenotypes were highly variable and heavily influenced by the degree of viremia. Although IL-2 induced significant expansions of CMV-specific CD8(+) T cells in LTNP and progressors by increasing both the numbers of cells entering the proliferating pool and the number of divisions, the proliferative capacity of a significant proportion of HIV-specific CD8(+) T cells was not restored with exogenous IL-2. These results suggest that immunodominance by HLA B5701-restricted cells is specific to HIV infection in LTNP and is not a feature of responses to other chronic viral infections. They also suggest that poor responsiveness to IL-2 is a property of HIV-specific CD8(+) T cells of progressors that is not shared with responses to other viruses over which immunologic control is maintained.

Difficulties in Transition of Care from Pediatric to Adult Gynecology Providers: Should We Maintain Care into Adulthood?

There is evidence that transfer of care for older adolescent patients to adult care is associated with a deterioration in health, especially in those with chronic conditions. Because several specific conditions in pediatric and adolescent gynecology continue into adulthood, it is important that patients have a seamless healthcare transition. In this commentary, it is argued that instead of arranging transfer, long-term retention of patients by the same physician or physician team may be the more caring, patient-centered approach.

Learning by looking: Infants' social looking behavior across the transition from crawling to walking.

This study investigated how infants gather information about their environment through looking and how that changes with increases in motor skills. In Experiment 1, 9.5- and 14-month-olds participated in a 10-min free play session with both a stranger and ambiguous toys present. There was a significant developmental progression from passive to active social engagement, as evidenced by younger infants watching others communicate more and older infants making more bids for social interaction. Experiment 2 examined longitudinally the impact of age and walking onset on this progression. The transition to independent walking marked significant changes in how often infants watched others communicate and made active bids for social interaction. Results suggest that infants transition from passive observers as crawlers to active participants in their social environment with the onset of walking.

Differential CMV-specific CD8+ effector T cell responses in the lung allograft predominate over the blood during human primary infection.

Acquisition of T cell responses during primary CMV infection in lung transplant recipients (LTRs) appear critical for host defense and allograft durability, with increased mortality in donor+/recipient- (D+R-) individuals. In 15 D+R- LTRs studied, acute primary CMV infection was characterized by viremia in the presence or absence of pneumonitis, with viral loads higher in the lung airways/allograft compared with the blood. A striking influx of CD8+ T cells into the lung airways/allograft was observed, with inversion of the CD4+:CD8+ T cell ratio. De novo CMV-specific CD8+ effector frequencies in response to pooled peptides of pp65 were strikingly higher in lung mononuclear cells compared with the PBMC and predominated over IE1-specific responses and CD4+ effector responses in both compartments. The frequencies of pp65-specific cytokine responses were significantly higher in lung mononuclear cells compared with PBMC and demonstrated marked contraction with long-term persistence of effector memory CD8+ T cells in the lung airways following primary infection. CMV-tetramer+CD8+ T cells from PBMC were CD45RA- during viremia and transitioned to CD45RA+ following resolution. In contrast, CMV-specific CD8+ effectors in the lung airways/allograft maintained a CD45RA- phenotype during transition from acute into chronic infection. Together, these data reveal differential CMV-specific CD8+ effector frequencies, immunodominance, and polyfunctional cytokine responses predominating in the lung airways/allograft compared with the blood during acute primary infection. Moreover, we show intercompartmental phenotypic differences in CMV-specific memory responses during the transition to chronic infection.

Aprt/Opn double knockout mice: osteopontin is a modifier of kidney stone disease severity.

BACKGROUND: Osteopontin (OPN) is reported to have two distinct functions in kidney disease: Promotion of inflammation at sites of tissue injury, and inhibition of calcium oxalate monohydrate stone formation. However, many of the studies supporting these functions were carried out in animal models of acute renal injury or in cultured cells; thus, the role of OPN in chronic renal disease is not well defined. We examined the role of OPN in adenine phosphoribosyltransferase (Aprt) knockout mice, in which inflammation and formation of 2,8-dihydroxyadenine (DHA) kidney stones are prominent features, by generating Aprt/Opn double knockout mice. METHODS: We characterized the phenotypes of six- and 12-week-old Aprt-/- Opn-/-, Aprt-/- Opn+/+, Aprt+/+ Opn-/-, and Aprt+/+ Opn+/+ male and female mice using biochemical, histologic, immunohistochemical, and in situ hybridization techniques. RESULTS: At 6 weeks of age, there was no difference in phenotype between double knockout and Aprt knockout mice. At 12 weeks, there was increased adenine and DHA excretion, renal crystal deposition, and inflammation in double knockout versus Aprt knockout male mice. Double knockout and Aprt knockout female mice at 12 weeks had less pathology than their male counterparts, but kidneys from double knockout females showed more inflammation compared with Aprt knockout females; both genotypes had similar levels of DHA crystal deposition. CONCLUSION: We conclude that (1) OPN is a major inhibitor of DHA crystal deposition and inflammation in male mice; and (2) OPN is a major modifier of the inflammatory response but not of crystal deposition in female mice. Thus, separate mechanisms appear responsible for the tissue changes seen in DKO males versus females.