Temporal trends in infection-related hospitalizations among patients with heart failure: A Danish nationwide study from 1997 to 2017.

BACKGROUND: Despite improved survival, hospitalization is still common among patients with heart failure (HF). OBJECTIVE: This study aimed to examine temporal trends in infection-related hospitalization among HF patients and compare it to temporal trends in the risk of HF hospitalization and death. METHODS: Using Danish nationwide registers, we included all patients aged 18 to 100 years, with HF diagnosed between January 1, 1997 and December 31, 2017, resulting in a total population of 147.737 patients. The outcomes of interest were primarily infection-related hospitalization and HF hospitalization and secondarily all-cause mortality. The Aalen Johansen's estimator was used to estimate 5-year absolute risks for the primary outcomes. Additionally, cox analysis was used for adjusted analyses. RESULTS: The population had a median age of 74 [64, 82] years and 57.6 % were males. Patients with HF had a higher risk of infection over time 16.4 % (95% CI 16.0-16.8) in 1997 to 2001 vs 24.5% (95% CI 24.0-24.9) in 2012 to 2017. In contrast, they had a lower risk of HF hospitalization 26.5% (95% CI 26.1-27.0) in 1997 to 2001 vs 23.2% (95% CI 22.8-23.7) in 2012 to 2017. The risk of infection stratified by infection type showed similar trends for all infection types and marked the risk of pneumonia infection as the most significant in all subintervals. CONCLUSION: In the period from 1997 to 2017, we observed patients with HF had an increased risk of infection-related hospitalization, driven by pneumonia infections. In contrast, the risk of HF hospitalization decreased over time.

Radiofrequency as a method of localizing impalpable breast lesions.

BACKGROUND: The incidence of early stage breast cancer has risen as a result of increased detection of non-palpable tumors through the implementation of screening programs and greater public awareness. Performing breast-conserving surgery can be challenging due to the need for accurate localization of non-palpable breast lesions, particularly given the logistical difficulties associated with wire localization. After implementing a new technique for localizing non-palpable breast lesions (LOCalizerTM Radiofrequency identification TAG-Hologic®), a radiofrequency identification tag localization device manufactured by Hologic, Inc. in Marlborough, MA, was launched in 2017, our objective was to investigate its impact on surgical outcomes, whether there was an increase in re-excision rates for positive margins and whether the attainment of clear margins was dependent on the exact positioning of the RFID device. METHOD: A single-center single-arm interventional study, data were gathered both in a forward-looking manner for 1 year (prospectively) and by looking back at past records for 1 year (retrospectively) for a total period of two years. Individuals who were diagnosed with non-palpable breast lesions, as confirmed by histological analysis, or invasive breast cancer and who were scheduled to undergo breast-conserving surgery were eligible for inclusion in the study. The RFID (Radiofrequency Identification) method was used to localize the lesions prior to surgery. Either with a mammogram or ultrasound scan position of the Tag was recorded, including the distance of the lesion from the center of the lesion and the lesion depth from the skin in millimeters. The rate of re-excision was documented and examined in relation to the parameters mentioned above. RESULTS: Two hundred and twenty RFID Tags were inserted in two hundred and seventeen (three patient had bilateral tags insertion), patients aged between 30 and 85 had a localizer Tag inserted between Oct 2020 and Oct 2022. Three patients had non-palpable breast lesions in both breasts. Fourteen were inserted under stereotactic guidance and two hundred and six under ultrasound guidance. Ten patients subsequently had wire insertion also due to Tag position. Of 210 procedures, RFIF Tags within the lesion was seen in hundred and sixty patients (76.19 %). An additional 50 procedures were performed using the RFID Tag system, which were not directly related to the lesion but were deemed appropriate to proceed with. Out of a total of 220 procedures, positive margins were observed in 38 cases (17.27 %). Among these cases, eleven (28.94 %) involved the use of the RFID Tag system, not within the lesion but adjacent to it (within 15 mm surrounding the lesion). CONCLUSION: RFID is a good alternative to wire localization of non-palpable breast lesions. Re-excision rates are higher in patients with Tag outside the lesion compared to those with Tag within the lesion.

Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.

OBJECTIVES: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ. METHODS: Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse. RESULTS: 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse. CONCLUSION: Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients.

Duodenal ulcer perforation and its consequences.

Duodenal ulcer perforation, a frequent surgical emergency, needs simple closure with indirect Graham's Omentopexy which is effective with excellent results in majority of cases despite patients' late presentation. The objective of the study was to determine the frequency of postoperative complications of perforated duodenal ulcer, conducted in the Surgery Department, Jinnah Postgraduate Medical Centre, Karachi, from March 20, 2018 to September 20, 2018. The study was a descriptive case series of 108 patients of both genders with perforated duodenal ulcer > 1 week old with ASA score I & II. Patients with trauma and comorbidities were excluded. The patients underwent laparotomy and peritoneal toilet, and after noting the site of perforation indirect Graham's Omentopexy was performed. Complications like duodenal fistula, peritonitis, and paralytic ileus, and patient's death within 10 days of surgery were noted. Age ranged from 18 to 50 years with mean age of 35.027±5.13 years, mean weight 71.120±12.77 kg, mean height 1.541 ±0.09 metres, mean BMI 29.975±4.99 kg/m2, and the mean duration of complaint was 4.194±1.30 weeks. Male predominance in 75 (69.4%) patients. Duodenal fistula was seen in 10 (9.3%) patients, peritonitis 12 (11.1%), paralytic ileus 14 (13%) and mortality was in 11 (10.2%) patients.

Approaches towards improving the quality of maternal and newborn health services in South Asia: challenges and opportunities for healthcare systems.

BACKGROUND: South Asia is experiencing a dismal state of maternal and newborn health (MNH) as the region has been falling behind in reducing the levels of maternal and neonatal mortality. Most of the efforts are focused on enhancing coverage of MNH services; however, quality remains a serious concern if the region is to achieve expected outcomes in terms of standardised MNH services within healthcare delivery systems. This research consists of a review of South Asian quality improvement (QI) approaches/interventions, specifically implemented for MNH improvement. METHODS: A literature review of QI approaches/interventions was conducted using the PRISMA guidelines. Online databases, including PubMed, the Cochrane Library and Google Scholar, were searched. Primary studies published between 1998 and 2013 were considered. Studies were initially screened and selected based upon the selection criteria for data extraction. A thematic synthesis/analysis was performed to organise, group and interpret the key findings according to prominent themes. RESULTS: Thirty studies from six South Asian countries were included in the review. Findings from these selected studies were grouped under eight broad, cross-cutting themes, which emerged from a deductive approach, representing the most commonly employed QI approaches for improving MNH services within different geographical settings. These consist of capacity building of healthcare providers on clinical quality, clinical audits and feedback, financial incentives to beneficiaries, pay-for-performance, supportive supervision, community engagement, collaborative efforts and multidimensional interventions. CONCLUSIONS: Employing and documenting QI approaches is essential in order to measure the potential of an intervention, considering its cost-effectiveness, feasibility and acceptability to communities. This research concluded that QI approaches are very diverse and cross-cutting, because they are subject to the varied requirements of regional health systems. This high level of variability leads to implementation and knowledge-management challenges for MNH programme planners and managers in the countries of the South Asia region.

Small ubiquitin-like modifier (SUMO)-mediated repression of the Xenopus Oocyte 5 S rRNA genes.

The 5 S rRNA gene-specific transcription factor IIIA (TFIIIA) interacts with the small ubiquitin-like modifier (SUMO) E3 ligase PIAS2b and with one of its targets, the transcriptional corepressor, XCtBP. PIAS2b is restricted to the cytoplasm of Xenopus oocytes but relocates to the nucleus immediately after fertilization. Following the midblastula transition, PIAS2b and XCtBP are present on oocyte-type, but not somatic-type, 5 S rRNA genes up through the neurula stage, as is a limiting amount of TFIIIA. Histone H3 methylation, coincident with the binding of XCtBP, also occurs exclusively on the oocyte-type genes. Immunohistochemical staining of embryos confirms the occupancy of a subset of the oocyte-type genes by TFIIIA that become positioned at the nuclear periphery shortly after the midblastula transition. Inhibition of SUMOylation activity relieves repression of oocyte-type 5 S rRNA genes and is correlated with a decrease in methylation of H3K9 and H3K27 and disruption of subnuclear localization. These results reveal a novel function for TFIIIA as a negative regulator that recruits histone modification activity through the CtBP repressor complex exclusively to the oocyte-type 5 S rRNA genes, leading to their terminal repression.

Inducible NOS-induced chloride intracellular channel 4 (CLIC4) nuclear translocation regulates macrophage deactivation.

Nuclear translocation of cytosolic CLIC4 is an essential feature of its proapoptotic and prodifferentiation functions. Here we demonstrate that CLIC4 is induced concurrently with inducible nitric oxide synthase (iNOS) and S-nitrosylated in proinflammatory peritoneal macrophages. Chemical inhibition or genetic ablation of iNOS inhibits S-nitrosylation and nuclear translocation of CLIC4. In macrophages, iNOS-induced nuclear CLIC4 coincides with the pro- to anti-inflammatory transition of the cells because IL-1ß and CXCL1 mRNA remain elevated in CLIC4 and iNOS knockout macrophages at late time points, whereas TNFα mRNA is elevated only in the iNOS knockout macrophages. Active IL-1ß remains elevated in CLIC4 knockout macrophages and in macrophages in which CLIC4 nuclear translocation is prevented by the NOS inhibitor l-NAME. Moreover, overexpression of nuclear-targeted CLIC4 down-regulates IL-1ß in stimulated macrophages. In mice, genetically null for CLIC4, the number of phagocytosing macrophages stimulated by LPS is reduced. Thus, iNOS-induced nuclear CLIC4 is an essential part of the macrophage deactivation program.

Determining the potential scalability of transport interventions for improving maternal, child, and newborn health in Pakistan.

BACKGROUND: Pakistan is far behind in achieving the Millennium Development Goals regarding the reduction of child and maternal mortality. Amongst other factors, transport barriers make the requisite obstetric care inaccessible for women during pregnancy and at birth, when complications may become life threatening for mother and child. The significance of efficient transport in maternal and neonatal health calls for identifying which currently implemented transport interventions have potential for scalability. METHODS: A qualitative appraisal of data and information about selected transport interventions generated primarily by beneficiaries, coordinators, and heads of organizations working with maternal, child, and newborn health programs was conducted against the CORRECT criteria of Credibility, Observability, Relevance, Relative Advantage, Easy-Transferability, Compatibility and Testability. Qualitative comparative analysis (QCA) techniques were used to analyse seven interventions against operational indicators. Logical inference was drawn to assess the implications of each intervention. QCA was used to determine simplifying and complicating factors to measure potential for scaling up of the selected transport intervention. RESULTS: Despite challenges like deficient in-journey care and need for greater community involvement, community-based ambulance services were managed with the support of the community and had a relatively simple model, and therefore had high scalability potential. Other interventions, including facility-based services, public-sector emergency services, and transport voucher schemes, had limitations of governance, long-term sustainability, large capital expenditures, and need for management agencies that adversely affected their scalability potential. CONCLUSION: To reduce maternal and child morbidity and mortality and increase accessibility of health facilities, it is important to build effective referral linkages through efficient transport systems. Effective linkages between community-based models, facility-based models, and public sector emergency services should be established to provide comprehensive coverage. Voucher scheme integrated with community-based services may bring improvements in service utilization.

Lost Connection: A Case Report of Interrupted Pituitary Stalk Syndrome.

Pituitary stalk interruption syndrome is a triad of thin (<1 mm) or complete absence of the pituitary stalk with either an aplastic or ectopic posterior lobe of the pituitary gland and a hypoplastic or absent anterior lobe of the pituitary. Patients present with growth retardation, short height, seizures, intellectual disability, and absence of sexual maturation at the expected time. Here, we presented a case of a 12-year-old male with stunted growth. Upon examination, there was reduced height, more than 3 standard deviations below the average for his chronological age. Laboratory results showed reduced levels of growth hormone and thyrotropin. Dual-energy X-ray absorptiometry revealed osteoporosis, while an X-ray of the wrist for bone age corresponded to seven years. MRI imaging confirmed the classical triad of findings for pituitary stalk interruption syndrome. Consequently, the patient was referred back to the endocrinology clinic for further management.

Chest Wall Synovial Sarcoma: A Unique Encounter at the Breast Base.

Synovial sarcomas most commonly arise in the para-articular locations of the extremities, such as the upper limbs, thigh, knee, ankle, and foot. Thoracic synovial sarcomas are a rare entity that can arise in the chest wall, pleura, lung, heart, or mediastinum. We present a case of a 23-year-old female with a complaint of swelling of the left breast. Examination demonstrated an enlarged left breast and a hard-fixed swelling without overlying skin changes or nipple retraction. Ultrasound showed a well-defined, solid-appearing lesion deep in the left breast parenchyma, which was adherent to the underlying left chest wall musculature and seemed to be displacing the breast parenchyma anteriorly. Contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) confirmed the lesion centered at the left pectoralis major and minor muscles, confirming the chest wall's origin. Histopathology findings favored monophasic synovial sarcoma.