Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

BACKGROUND: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. METHODS: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. RESULTS: The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. CONCLUSIONS: Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.

Completion of isoniazid preventive therapy for latent tuberculosis infection among children and adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: Little is known about isoniazid preventive therapy (IPT) completion rates among children or adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: We conducted a retrospective cohort analysis including children, adolescents, and adults living with HIV who were treated at FHI360 and partners-implemented HIV care programs at six health zones in Kinshasa, DRC, from 2004 to 2020. The primary outcome was the proportion of children, adolescents versus adults who did complete 6 months of daily self-administered IPT. Log-binomial regression assessed independent predictors of IPT non-completion and Kaplan-Meier technique for survival analysis. RESULTS: Of 11,691 eligible patients on ART who initiated IPT, 429 were children (<11 years), 804 adolescents (11-19 years), and 10,458 adults (≥20 years). The median age was 7 (IQR: 3-9) years for children, 15 (IQR: 13-17) years for adolescents, and 43 (35-51) years for adults. Among those who were initiated on IPT, 5625 out of 11,691 people living with HIV (PLHIV) had IPT completion outcome results, and an overall 3457/5625 (61.5%) completion rate was documented. Compared to adults, children and adolescents were less likely to complete IPT [104/199 (52.3%) and 268/525 (51.0%), respectively, vs. 3085/4901 (62.9%)]. After adjustment, the only independent predictors for IPT non-completion were health zone of residence and type of ART regimen. Kaplan-Meier analysis showed comparable poor survival among patients who completed IPT versus those who did not (p-value for log-rank test, 0.15). CONCLUSIONS: The overall sub-optimal IPT completion rate in adults as well as children/adolescents in this setting is of great concern. Prospective studies are needed to elucidate the specific barriers to IPT completion among children, adolescents, and adults in DRC as well as the scale-up of evidence-informed interventions to improve IPT completion, such as adoption of shorter TB preventive regimens.

Trans-Omics analysis of post injury thrombo-inflammation identifies endotypes and trajectories in trauma patients.

Understanding and managing the complexity of trauma-induced thrombo-inflammation necessitates an innovative, data-driven approach. This study leveraged a trans-omics analysis of longitudinal samples from trauma patients to illuminate molecular endotypes and trajectories that underpin patient outcomes, transcending traditional demographic and physiological characterizations. We hypothesize that trans-omics profiling reveals underlying clinical differences in severely injured patients that may present with similar clinical characteristics but ultimately have very different responses to treatment and clinical outcomes. Here we used proteomics and metabolomics to profile 759 of longitudinal plasma samples from 118 patients at 11 time points and 97 control subjects. Results were used to define distinct patient states through data reduction techniques. The patient groups were stratified based on their shock severity and injury severity score, revealing a spectrum of responses to trauma and treatment that are fundamentally tied to their unique underlying biology. Ensemble models were then employed, demonstrating the predictive power of these molecular signatures with area under the receiver operating curves of 80 to 94% for key outcomes such as INR, ICU-free days, ventilator-free days, acute lung injury, massive transfusion, and death. The molecularly defined endotypes and trajectories provide an unprecedented lens to understand and potentially guide trauma patient management, opening a path towards precision medicine. This strategy presents a transformative framework that aligns with our understanding that trauma patients, despite similar clinical presentations, might harbor vastly different biological responses and outcomes.

Keeping essential reproductive, maternal and child health services available during COVID-19 in Kenya, Mozambique, Uganda and Zimbabwe: analysis of early-pandemic policy guidelines.

BACKGROUND: The COVID-19 pandemic has disrupted the provision of essential reproductive, maternal, newborn, and child health (RMNCH) services in sub-Saharan Africa to varying degrees. Original models estimated as many as 1,157,000 additional child and 56,700 maternal deaths globally due to health service interruptions. To reduce potential impacts to populations related to RMNCH service delivery, national governments in Kenya, Mozambique, Uganda, and Zimbabwe swiftly issued policy guidelines related to essential RMNCH services during COVID-19. The World Health Organization (WHO) issued recommendations to guide countries in preserving essential health services by June of 2020. METHODS: We reviewed and extracted content related to family planning (FP), antenatal care (ANC), intrapartum and postpartum care and immunization in national policies from Kenya, Uganda, Mozambique, and Zimbabwe from March 2020 to February 2021, related to continuation of essential RMNCH services during the COVID-19 pandemic. Using a standardized tool, two to three analysts independently extracted content, and in-country experts reviewed outputs to verify observations. Findings were entered into NVivo software and categorized using pre-defined themes and codes. The content of each national policy guideline was compared to WHO guidance related to RMNCH essential services during COVID-19. RESULTS: All four country policy guidelines considered ANC, intrapartum care, FP, and immunization to be essential services and issued policy guidance for continuation of these services. Guidelines were issued in April 2020 by Mozambique, Kenya, and Uganda, and in June 2020 by Zimbabwe. Many elements of WHO's 2020 recommendations were included in country policies, with some notable exceptions. Each policy guideline was more detailed in some aspects than others - for example, Kenya's guidelines were particularly detailed regarding FP service provision, while Uganda's guidelines were explicit about immediate breastfeeding. All policy guidance documents contained a balance of measures to preserve essential RMNCH services while reducing COVID-19 transmission risk within these services. CONCLUSIONS: The national policy guidelines to preserve essential RMNCH services in these four countries reflected WHO recommendations, with some notable exceptions for ANC and birth companionship. Ongoing revision of country policy guidelines to adapt to changing pandemic conditions is recommended, as is further analysis of subnational-level policies.

Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature - The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11).

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature - The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11).

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

mTOR-driven glycolysis governs induction of innate immune responses by bronchial epithelial cells exposed to the bacterial component flagellin.

Human bronchial epithelial (HBE) cells play an essential role during bacterial infections of the airways by sensing pathogens and orchestrating protective immune responses. We here sought to determine which metabolic pathways are utilized by HBE cells to mount innate immune responses upon exposure to a relevant bacterial agonist. Stimulation of HBE cells by the bacterial component flagellin triggered activation of the mTOR pathway resulting in an increased glycolytic flux that sustained the secretory activity of immune mediators by HBE cells. The mTOR inhibitor rapamycin impeded glycolysis and limited flagellin-induced secretion of immune mediators. The role of the mTOR pathway was recapitulated in vivo in a mouse model of flagellin-triggered lung innate immune responses. These data demonstrate that metabolic reprogramming via the mTOR pathway modulates activation of the respiratory epithelium, identifying mTOR as a potential therapeutic target to modulate mucosal immunity in the context of bacterial infections.

Perceptions and understanding about mesh and hernia surgery: What do patients really think?

BACKGROUND: Surgical mesh and hernia repair have come under increasing scrutiny with large amounts of press, Internet, and social media reportage regarding ongoing mesh litigation, recalls, and patient testimonials. The aim of this study was to evaluate patient perceptions of mesh in hernia surgery. METHODS: A 16-question survey was given to patients presenting for hernia surgery at a tertiary hernia center by trained data analysts before surgeon interaction. RESULTS: Two hundred and two patients were surveyed. Patients believed mesh caused complications (45.1%) and reported concerns about mesh (38.2%). Those who performed their own research, females, and patients with recurrent hernias were more likely to have concerns about mesh (P ≤ 0.03). Most patients (81.7%) thought they were at average risk or less for complications; patients with recurrent hernias (versus primary hernias) and incisional hernias (compared with inguinal or umbilical hernias) had more negative outlooks on complications (all P < .05). Recovery expectations varied, but the failed repair and incisional hernia groups were more likely to expect prolonged recovery (>3 months) (all P < .05). After surgeon-directed education and a mesh education handout, all but one patient agreed to and underwent a mesh repair as indicated. CONCLUSION: Patients had concerns about mesh and were aware of mesh related complications. Patients performing their own research, as well as females and recurrent hernia patients, had worse perceptions of mesh. Recurrent and incisional hernia patients had greater concerns about complications, recurrence, and recovery. Preoperative education concerning mesh and mesh choice for each operation eased patient anxiety.

Preoperative patient opioid education, standardization of prescriptions, and their impact on overall patient satisfaction.

BACKGROUND: The opioid epidemic has reached a crisis level in America, and many institutions are implementing new guidelines to decrease opioid prescriptions. Although these may positively impact opioid addiction, its influence on patient satisfaction is inadequately described. The aim of the study was to evaluate the effect of standardized patient education and postoperative opioid regimens on patient satisfaction. METHODS: General surgery patients were counselled and given educational materials preoperatively regarding postoperative pain management. Inpatient discharge prescriptions were based on milligrams of oral narcotic required 24 hours before discharge. Outpatient procedure prescriptions were standardized. Postoperatively, patients received surveys regarding pain control and satisfaction. RESULTS: Of the 198 patients studied, 96% agreed or strongly agreed that they were satisfied with their pain control. 92% agreed or strongly agreed they received enough medication; 7% disagreed, and 1% strongly disagreed. Educational materials were evaluated with 97% agreeing or strongly agreeing they received appropriate information concerning when and what to take. Fifty-five patients (28%) refused opioids or did not take any. Only 10 (5%) requested a refill. CONCLUSION: Preoperative education and standardized postoperative narcotic prescribing can be highly effective while maintaining high patient satisfaction. Introduction across broad fields of surgery will allow uniformity for surgeons, trainees, nurses, pharmacists, and patients.

Sarcopenia in Patients Undergoing Open Ventral Hernia Repair.

Radiologic indicators of sarcopenia have been associated with adverse operative outcomes in some surgical populations. This study assesses the association of radiologic indicators of frailty with outcomes after open ventral hernia repair (OVHR). A prospective, institutional, hernia-specific database was queried for patients undergoing OVHR from 2007 to 2018 with preoperative CT. Psoas muscle cross-sectional area at L3 was measured and adjusted for height (skeletal muscle index (SMI)). L3 vertebral body density (L3 VBD) was measured. Demographics and outcomes were evaluated as related to SMI and L3 VBD. Of 1178 patients, 9.7 per cent of females and 15.8 per cent of males had sarcopenia and 11.6 per cent of females and 9.2 per cent of males had osteopenia. Neither sarcopenia nor osteopenia were associated with outcomes of wound infection, readmission, reoperation, hernia recurrence, or major complications. When examined as continuous variables or by quartile, SMI and L3 VBD were not associated with adverse outcomes, including in subsets of male or female patients, the elderly, contaminated cases, and the obese. Radiologic markers of sarcopenia and osteopenia are not associated with adverse outcomes after OVHR. Further study should examine age or other potential predictors of outcomes in this patient population, such as independent status.

Sustained high HIV case-finding through index testing and partner notification services: experiences from three provinces in Zimbabwe.

INTRODUCTION: Several countries in southern Africa have made significant progress towards reaching the Joint United Nations Programme on HIV/AIDS goal of ensuring that 90% of people living with HIV are aware of their status. In Zimbabwe, progress towards this "first 90" was estimated at 73% in 2016. To reach the remaining people living with HIV who have undiagnosed infection, the Zimbabwe Ministry of Health and Child Care has been promoting index testing and partner notification services (PNS). We describe the implementation of index testing and PNS under the Zimbabwe HIV Care and Treatment (ZHCT) project and the resulting uptake, HIV positivity rate and links to HIV treatment. METHODS: The ZHCT project has been implemented since March 2016, covering a total of 12 districts in three provinces. To assess the project's performance on index testing, we extracted data on HIV testing from the district health information system (DHIS 2) from March 2016 to May 2018, validated it using service registers and calculated monthly HIV positivity rates using Microsoft Excel. Data were disaggregated by district, province, sex and service delivery point. We used SPSS to assess for statistical differences in paired monthly HIV positivity rates by sex, testing site, and province. RESULTS: The average HIV positivity rate rose from 10% during the first six months of implementation to more than 30% by August 2016 and was sustained above 30% through May 2018. The overall facility HIV positivity rate was 4.1% during the same period. The high HIV positivity rate was achieved for both males and females (mean monthly HIV positivity rate of 31.3% for males and 33.7% for females), with females showing significantly higher positivity compared to males (p < 0.001). The ZHCT mean monthly HIV positivity rate from index testing (32.6%) was significantly higher than that achieved through provider-initiated testing and counselling and other facility HIV testing modalities (4.1%, p < 0.001). CONCLUSIONS: The ZHCT project has demonstrated successes in implementing index testing and PNS by attaining a high HIV positivity rate sustained over the study period. As the country moves towards HIV epidemic control, index testing and PNS are critical strategies for targeted HIV case identification.

Impact of acute kidney injury on neurological outcome and long-term survival after cardiac arrest - A 10 year observational follow up.

BACKGROUND: Acute kidney injury (AKI) may be associated with short- and long-term patient morbidity and mortality. Therefore, the impact of AKI after cardiac arrest on survival and neurological outcome was evaluated. METHODS: An observational single center study was conducted and consecutively included all out and in hospital cardiac arrest (OHCA/IHCA) patients treated with therapeutic temperature management between 2006 and 2013. Patient morbidity, mortality and neurological outcome according to the widely used Pittsburgh Cerebral Performance Category (CPC) were assessed. A good neurological outcome was defined as a CPC of 1-2 versus a poor neurological outcome with a CPC of 3-5. AKI was defined by using the KDIGO Guidelines 2012. RESULTS: 503 patients were observed in total. 29.4% (n = 148) developed AKI during their intensive care unit (ICU) stay. 70.6% (n = 355) did not experience AKI. The mean age at admission was 62 years, of those 72.8% were male and 77% experienced an out-of-hospital cardiac arrest (OHCA). AKI occurred with 41.2% more often in the group with poor neurological outcome compared to 17.1% in the group with good neurological outcome. The median survival for patients after cardiac arrest with AKI was 0.07 years compared to 6.5 years for patients without AKI. CONCLUSION: Our data suggest that AKI is a major risk factor for a poor neurological outcome and a higher mortality after cardiac arrest. Further important risk factors were age, time to ROSC and high NSE.

Classification of Ventricular Septal Defects for the Eleventh Iteration of the International Classification of Diseases-Striving for Consensus: A Report From the International Society for Nomenclature of Paediatric and Congenital Heart Disease.

The definition and classification of ventricular septal defects have been fraught with controversy. The International Society for Nomenclature of Paediatric and Congenital Heart Disease is a group of international specialists in pediatric cardiology, cardiac surgery, cardiac morphology, and cardiac pathology that has met annually for the past 9 years in an effort to unify by consensus the divergent approaches to describe ventricular septal defects. These efforts have culminated in acceptance of the classification system by the World Health Organization into the 11th Iteration of the International Classification of Diseases. The scheme to categorize a ventricular septal defect uses both its location and the structures along its borders, thereby bridging the two most popular and disparate classification approaches and providing a common language for describing each phenotype. Although the first-order terms are based on the geographic categories of central perimembranous, inlet, trabecular muscular, and outlet defects, inlet and outlet defects are further characterized by descriptors that incorporate the borders of the defect, namely the perimembranous, muscular, and juxta-arterial types. The Society recognizes that it is equally valid to classify these defects by geography or borders, so the emphasis in this system is on the second-order terms that incorporate both geography and borders to describe each phenotype. The unified terminology should help the medical community describe with better precision all types of ventricular septal defects.

Nomenclature for congenital and paediatric cardiac disease: the International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Iteration of the International Classification of Diseases (ICD-11).

An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many "short list" versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various "short lists". In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the "short list" for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.

Removal of micropollutants with coarse-ground activated carbon for enhanced separation with hydrocyclone classifiers.

One key technology to eliminate organic micropollutants (OMP) from wastewater effluent is adsorption using powdered activated carbon (PAC). To avoid a discharge of highly loaded PAC particles into natural water bodies a separation stage has to be implemented. Commonly large settling tanks and flocculation filters with the application of coagulants and flocculation aids are used. In this study, a multi-hydrocyclone classifier with a downstream cloth filter has been investigated on a pilot plant as a space-saving alternative with no need for a dosing of chemical additives. To improve the separation, a coarser ground PAC type was compared to a standard PAC type with regard to elimination results of OMP as well as separation performance. With a PAC dosing rate of 20 mg/l an average of 64.7 wt% of the standard PAC and 79.5 wt% of the coarse-ground PAC could be separated in the hydrocyclone classifier. A total average separation efficiency of 93-97 wt% could be reached with a combination of both hydrocyclone classifier and cloth filter. Nonetheless, the OMP elimination of the coarse-ground PAC was not sufficient enough to compete with the standard PAC. Further research and development is necessary to find applicable coarse-grained PAC types with adequate OMP elimination capabilities.

Complex atrial arrhythmias as first manifestation of catecholaminergic polymorphic ventricular tachycardia: an unusual course in a patient with a new mutation in ryanodine receptor type 2 gene.

Catecholaminergic polymorphic ventricular tachycardia is a rare life-threatening arrhythmogenic disorder. An association with paroxysmal atrial fibrillation and other atrial arrhythmias has been described, but in all published cases the initial manifestation of the disease was ventricular arrhythmia. This is the first report about a patient who presented with complex atrial tachycardia and sinus node dysfunction about 1 year before the typical ventricular arrhythmias were observed, leading to the diagnosis of catecholaminergic polymorphic ventricular tachycardia. In this girl, a mutation of the ryanodine receptor type 2 gene, which has not been described so far, was discovered.

The effectiveness of community based distribution of injectable contraceptives using community health extension workers in Gombe State, Northern Nigeria.

This study reports on findings of a pilot of community-based distribution (CBD) of injectable contraceptives in two local government areas (LGAs) of Gombe State, Nigeria. From August 2009 to January 2010, the project enrolled, trained and equipped community health extension workers (CHEWs) to distribute condoms, oral and injectable contraceptives in communities. The project mobilized communities and stakeholders to promote Family Planning (FP) services in the selected communities. Using anonymised unlinked routine service data, the mean couple years of protection (CYP) achieved through CBD was compared to that achieved in FP clinics. The CBD mean CYP for injectables- depo medroxy-progesterone acetate (DMPA) and norethisterone enantate was higher (27.72 & 18.16 respectively) than the facility CYP (7.21 & 5.08 respectively) (p < 0.05) with no injection related complications. The CBD's mean CYP for all methods was also found to be four times higher (11.65) than that generated in health facilities (2.86) (p < 0.05). This suggests that the CBD of injectable contraceptives is feasible and effective, even in a setting like northern Nigeria that has sensitivities about FP.

Patients' demographic and clinical characteristics and level of care associated with lost to follow-up and mortality in adult patients on first-line ART in Nigerian hospitals.

INTRODUCTION: Clinical outcome is an important determinant of programme success. This study aims to evaluate patients' baseline characteristics as well as level of care associated with lost to follow-up (LTFU) and mortality of patients on antiretroviral treatment (ART). METHODS: Retrospective cohort study using routine service data of adult patients initiated on ART in 2007 in 10 selected hospitals in Nigeria. We captured data using an electronic medical record system and analyzed using Stata. Outcome measures were probability of being alive and retained in care at 12, 24 and 36 months on ART. Potential predictors associated with time to mortality and time to LTFU were assessed using competing risks regression models. RESULTS: After 12 months on therapy, 85% of patients were alive and on ART. Survival decreased to 81.2% and 76.1% at 24 and 36 months, respectively. Median CD4 count for patients at ART start, 12, 18 and 24 months were 152 (interquartile range, IQR: 75 to 242), 312 (IQR: 194 to 450), 344 (IQR: 227 to 501) and 372 (IQR: 246 to 517) cells/µl, respectively. Competing risk regression showed that patients' baseline characteristics significantly associated with LTFU were male (adjusted sub-hazard ratio, sHR = 1.24 [95% CI: 1.08 to 1.42]), ambulatory functional status (adjusted sHR = 1.25 [95% CI: 1.01 to 1.54]), World Health Organization (WHO) clinical Stage II (adjusted sHR = 1.31 [95% CI: 1.08 to 1.59]) and care in a secondary site (adjusted sHR = 0.76 [95% CI: 0.66 to 0.87]). Those associated with mortality include CD4 count < 50 cells/µl (adjusted sHR = 2.84 [95% CI: 1.20 to 6.71]), WHO clinical Stage III (adjusted sHR = 2.67 [95% CI: 1.26 to 5.65]) and Stage IV (adjusted sHR = 5.04 [95% CI: 1.93 to 13.16]) and care in a secondary site (adjusted sHR = 2.21 [95% CI: 1.30 to 3.77]). CONCLUSIONS: Mortality was associated with advanced HIV disease and care in secondary facilities. Earlier initiation of therapy and strengthening systems in secondary level facilities may improve retention and ultimately contribute to better clinical outcomes.

Reducing mother-to-child transmission of HIV: findings from an early infant diagnosis program in south-south region of Nigeria.

BACKGROUND: Early diagnosis of HIV in infants provides a critical opportunity to strengthen follow-up of HIV-exposed children and assure early access to antiretroviral (ARV) treatment for infected children. This study describes findings from an Early Infant Diagnosis (EID) program and the effectiveness of a prevention of mother-to-child transmission (PMTCT) intervention in six health facilities in Cross-River and Akwa-Ibom states, south-south Nigeria. METHODS: This was a retrospective study. Records of 702 perinatally exposed babies aged six weeks to 18 months who had a DNA PCR test between November 2007 and July 2009 were reviewed. Details of the ARV regimen received to prevent mother-to-child transmission (MTCT), breastfeeding choices, HIV test results, turn around time (TAT) for results and post test ART enrolment status of the babies were analysed. RESULTS: Two-thirds of mother-baby pairs received ARVs and 560 (80%) babies had ever been breastfed. Transmission rates for mother-baby pairs who received ARVs for PMTCT was 4.8% (CI 1.3, 8.3) at zero to six weeks of age compared to 19.5% (CI 3.0, 35.5) when neither baby nor mother received an intervention. Regardless of intervention, the transmission rates for babies aged six weeks to six months who had mixed feeding was 25.6% (CI 29.5, 47.1) whereas the transmission rates for those who were exclusively breastfed was 11.8% (CI 5.4, 18.1). Vertical transmission of HIV was eight times (AOR 7.8, CI: 4.52-13.19) more likely in the sub-group of mother-baby pairs who did not receive ARVS compared with mother-baby pairs that did receive ARVs. The median TAT for test results was 47 days (IQR: 35-58). A follow-up of 125 HIV positive babies found that 31 (25%) were enrolled into a paediatric ART program, nine (7%) were known to have died before the return of their DNA PCR results, and 85 (67%) could not be traced and were presumed to be lost-to-follow-up. CONCLUSION: Reduction of MTCT of HIV is possible with effective PMTCT interventions, including improved access to ARVs for PMTCT and appropriate infant feeding practices. Loss to follow up of HIV exposed infants is a challenge and requires strategies to enhance retention.

The proline TP53 variant stimulates likely lymphangiogenesis in an orthotopic mouse model of pancreatic cancer.

BACKGROUND: Pancreatic cancer is a deadly disease characterised by high incidence of TP53 mutations. Restoration of TP53 function is perceived as a highly attractive therapeutic strategy, whose effects are not well characterised. METHODS: The current work adapted an inducible strategy of stage-specific reexpression of wild-type (wt) TP53 in an in vivo orthotopic mouse model of pancreatic cancer. RESULTS: The reconstitution of wt TP53 function in TP53-mutant DanG and MiaPaCa-2 cells caused G1 cell cycle arrest but no evidence of apoptosis induction. Consistent with subcutaneous xenograft models, we found that wt TP53 reduced primary tumour growth. Wt TP53 reexpression during early tumour growth led to significant increase in vascularisation. This correlated with an unexpectedly high rate of micro-metastases in lymph nodes of animals with wt TP53 induction, despite the 90% decrease in median primary tumour weight. Reexpression of wt TP53 later in tumour development did not significantly affect the number of CD31-reactive vessels, but increased lymphatic vessel density. CONCLUSION: The increased number of lymphatic vessels and micro-metastases suggests that wt TP53 induction complexly affected the biology of different tumour constituents of pancreatic cancer. Our observation suggests that combination of the inducible system with an orthotopic model can yield important insights into in vivo pancreatic cancer biology.