Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia / RYR1 myopathies in childhood: phenotype-genotype correlation and incidence

Introducción: Las miopatías relacionadas con el receptor de rianodina de tipo 1 (RYR1-RM) constituyen la categoría más frecuente de miopatías congénitas. La introducción de técnicas genéticas ha cambiado el paradigma diagnóstico y sugiere la prioridad de estudios moleculares sobre biopsias. Este estudio busca explorar las características clinicoepidemiológicas de pacientes con variantes del gen RYR1 en un hospital pediátrico de tercer nivel con el objetivo de ampliar la comprensión de la correlación genotipo-fenotipo en las RYR1-RM. Pacientes y métodos: Estudio observacional, descriptivo y transversal, de pacientes menores de 14 años con síntomas miopáticos y variantes potencialmente patógenas del gen RYR1 entre enero de 2013 y diciembre de 2023, considerando variables como sexo, edad, desarrollo motor, variantes genéticas, patrón de herencia y otras manifestaciones. Todas las variables fueron tabuladas frente a la variante genética. Resultados: De los nueve pacientes incluidos, la incidencia estimada fue de aproximadamente 1/10.000 nacidos vivos. La mediana en el momento del diagnóstico fue de 6 años, con una variabilidad fenotípica significativa. Se observaron síntomas comunes, como debilidad y retraso del desarrollo motor. Las variantes genéticas afectaron al gen RYR1 de manera diversa, y hubo cinco variantes previamente no descritas. La biopsia muscular se realizó en cinco pacientes, en dos de ellos de tipo miopatía central core; en uno, multiminicore; en uno, desproporción congénita de fibras; y en otro, de patrón inespecífico. Conclusiones: Las RYR1-MR de nuestra serie ofrecieron variabilidad fenotípica y de afectación, con una incidencia en nuestra área de en torno a 1/10.000 recién nacidos. La mayoría de los casos fueron varones, de variantes missense dominantes. Aportamos cinco variantes genéticas no descritas con anterioridad.(AU)

Introduction: Ryanodine receptor type 1-related myopathies (RYR1-RM) represent the most prevalent category of congenital myopathies. The introduction of genetic techniques has shifted the diagnostic paradigm, suggesting the prioritization of molecular studies over biopsies. This study aims to explore the clinical and epidemiological characteristics of patients with RYR1 gene variants in a tertiary pediatric hospital, intending to enhance the understanding of the genotype-phenotype correlation in RYR1-RM. Patients and methods: An observational, descriptive, and cross-sectional study was conducted on patients under 14 years old with myopathic symptoms and potentially pathogenic RYR1 gene variants from January 2013 to December 2023. Variables such as gender, age, motor development, genetic variants, inheritance pattern, and other manifestations were considered. All variables were tabulated against the genetic variant. Results: Of the nine included patients, the estimated incidence was approximately 1 in 10,000 live births. The median age at diagnosis was six years, with significant phenotypic variability. Common symptoms such as weakness and delayed motor development were observed. Genetic variants affected the RYR1 gene diversely, including five previously undescribed variants. Muscle biopsy was performed in five patients, revealing central core myopathy in two, multiminicore in one, congenital fiber-type disproportion in one, and a nonspecific pattern in another.(AU)

The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients.

Cytochromes P450 (CYPs) play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75% of the total metabolism of commercially available drugs, including chemotherapeutics. The gene expression and enzyme activity of CYPs are variable between individuals, which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics, as well as differences in the efficacy and toxicity of clinically used drugs. This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients, as well as the clinical outcome after receiving cyclophosphamide chemotherapy. DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex- and age-matched healthy individuals. The presence of the CYP2B6*9 (G516T) polymorphism was examined by PCR-based allele specific amplification (ASA). Patients were further indicated for receiving chemotherapy, and then they were followed up. The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models, comprising allelic (T-allele vs. G-allele, OR = 4.8, p < 0.001) and dominant (GT + TT vs. GG, OR = 5.4, p < 0.001) models. Following cyclophosphamide chemotherapy, we found that the patients with variant genotypes (GT + TT) were less likely to achieve remission compared to those with the wild-type genotype (GG), with a response percentage of (37.5% vs. 83%, respectively). In conclusion, our findings showed that the CYP2B6*9 (G516T) polymorphism is associated with B-CLL susceptibility among Egyptian patients. This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

Epidemiology of and programmatic response to tuberculosis in Solomon Islands: analysis of surveillance data, 2016-2022.

Objective: To identify progress and challenges in the national response to tuberculosis (TB) in Solomon Islands through an epidemiological overview of TB in the country. Methods: A descriptive analysis was conducted using the national TB surveillance data for 2016-2022. Case notifications, testing data, treatment outcomes and screening activities were analysed. Results: The number of case notifications was 343 in 2022, with an average annual reduction of the case notification rate between 2016 and 2022 of 4.7%. The highest case notification rate was reported by Honiara City Council (126/100 000 population) in 2022. The number of people with presumptive TB tested by Xpert® rapidly increased from zero in 2016 to 870 in 2022. Treatment success rate remained consistently high between 2016 and 2022, ranging from 92% to 96%. Screening for HIV and diabetes mellitus (DM) among TB patients in 2022 was 14% and 38%, respectively. Most patients (97%) were hospitalized during the intensive phase of treatment in 2022; in contrast, during the continuation phase, the proportion of patients treated at the community level increased from 1% in 2016 to 63% in 2022. Despite an increase in household contact investigations, from 381 in 2016 to 707 in 2021, the uptake of TB preventive treatment (TPT) was minimal (7% among eligible child contacts). Discussion: This epidemiological analysis in Solomon Islands reveals both notable achievements and challenges in the country's TB programme. One major achievement is a potential actual reduction in TB incidence. Challenges identified were potential underdetection of cases in rural areas, suboptimal community-based care, and insufficient contact tracing and uptake of TPT. It is crucial to address these challenges (e.g. by optimizing resources) to advance the national TB response.

[Screening for cutaneous melanoma: little impact, major challenges]. / Dépistage du mélanome : peu d'impact, beaucoup de défis.

Routine screening for melanoma has never been shown to be effective. Here, we revisit this debate and the preconceived notion that the increased detection of early-stage melanoma should necessarily be followed within the same population by a reduction in the incidence of advanced stages, which is not supported by any evidence. The issue of overdiagnosis, which has been debated for several decades, is discussed in the light of screening practices. We illustrate with two of its common motives, why this practice is ineffective. Finally, we suggest that the risk of overdiagnosis has probably reached its climax over the last two decades, as the increasing sensitivity of skin-imaging tools has not been followed by a refinement of histopathologic diagnostic criteria.

Le dépistage systématique du mélanome n'a jamais fait la preuve de son efficacité. Nous rediscutons ici de cette question en revenant sur l'idée reçue que le dépistage accru des stades précoces de mélanome au sein d'une population devrait engendrer une diminution des formes avancées de la maladie, ce qui ne se vérifie pas dans les faits. La question débattue depuis plusieurs décennies du surdiagnostic est également discutée à la lumière des pratiques de dépistage. Nous illustrons par deux motifs fréquents de dépistage pourquoi cette pratique est inefficace. Nous suggérons que le risque de surdiagnostic a atteint son paroxysme au cours des deux dernières décennies dans la mesure où la sensibilité croissante des outils d'imagerie cutanée n'a pas été suivie d'un affinement des critères diagnostiques histopathologiques.

Understanding the impact of adult pertussis and current approaches to vaccination: A narrative review and expert panel recommendations.

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.

Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study.

BACKGROUND: The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk. METHODS: The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan-Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count. RESULTS: During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan-Meier curves. The adjusted HR (95% CI) for incident CVD in Q2-Q4, compared with Q1, was 1.47 (1.12-1.93), 1.91 (1.44-2.54) and 2.24 (1.63-3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease. CONCLUSIONS: The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.

Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis.

INTRODUCTION: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer. METHODS AND ANALYSIS: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis. ETHICS AND DISCLOSURE: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235163.

Incidence, treatment, and factors associated with survival of out-of-hospital cardiac arrest attended by Spanish emergency services: report from the Out-of-Hospital Spanish Cardiac Arrest Registry for 2022. / Incidencia, tratamiento y factores asociados con la supervivencia de la parada cardiaca extrahospitalaria atendida por los servicios de emergencias en España: informe 2022 del registro OHSCAR.

SUMMARY: Out-of-hospital cardiac arrest is a serious public health problem worldwide. The annual incidence is estimated at around 400 000 cases in Europe and the United States, and survival rates scarcely reach 10%. However, there is considerable variation between countries and even between regions that share a similar health care system within a single country. Information recorded by the Out-of-Hospital Spanish Cardiac Arrest Registry (OHSCAR) provides information on care provided by emergency ambulance services, final health outcomes after cardiac arrest cases (including variations), the possibility of organ donation, and the impact of the COVID-19 pandemic. This paper presents the OHSCAR report for Spanish emergency services for the year 2022.

RESUMEN: La parada cardiorrespiratoria extrahospitalaria (PCREH) es un grave problema de salud pública mundial, con una incidencia anual estimada entorno a entorno a los 350.000 y 400.000 casos de PCERH en Europa y Estados Unidos, respectivamente. La supervivencia final se sitúa en porcentajes que apenas alcanzan el 10%, aunque existe una importante variabilidad entre países e incluso entre regiones del mismo país con modelos de atención similares. En España, el Registro Español de Parada Cardiaca Extrahospitalaria (acrónimo OHSCAR) ha ofrecido información sobre la asistencia a la PCRE prestada por los servicios de emergencias (SEM) y sus resultados finales en salud, así como sobre variabilidad, posibilidades de programas de donación o impacto de la pandemia COVID-19. A continuación se presenta el informe OHSCAR correspondiente a la asistencia a la PCRE por los SEM españoles durante el año 2022.

Have the recent advancements in cancer therapy and survival benefitted patients of all age groups across the Nordic countries? NORDCAN survival analyses 2002-2021.

BACKGROUND: Since the early 2000s, overall and site-specific cancer survival have improved substantially in the Nordic countries. We evaluated whether the improvements have been similar across countries, major cancer types, and age groups. MATERIAL AND METHODS: Using population-based data from the five Nordic cancer registries recorded in the NORDCAN database, we included a cohort of 1,525,854 men and 1,378,470 women diagnosed with cancer (except non-melanoma skin cancer) during 2002-2021, and followed for death until 2021. We estimated 5-year relative survival (RS) in 5-year calendar periods, and percentage points (pp) differences in 5-year RS from 2002-2006 until 2017-2021. Separate analyses were performed for eight cancer sites (i.e. colorectum, pancreas, lung, breast, cervix uteri, kidney, prostate, and melanoma of skin). RESULTS: Five-year RS improved across nearly all cancer sites in all countries (except Iceland), with absolute differences across age groups ranging from 1 to 21 pp (all cancer sites), 2 to 20 pp (colorectum), -1 to 36 pp (pancreas), 2 to 28 pp (lung), 0 to 9 pp (breast), -11 to 26 pp (cervix uteri), 2 to 44 pp (kidney), -2 to 23 pp (prostate) and -3 to 30 pp (skin melanoma). The oldest patients (80-89 years) exhibited lower survival across all countries and sites, although with varying improvements over time. INTERPRETATION: Nordic cancer patients have generally experienced substantial improvements in cancer survival during the last two decades, including major cancer sites and age groups. Although survival has improved over time, older patients remain at a lower cancer survival compared to younger patients.

Impact of the COVID-19 pandemic on lymphoma incidence and short-term survival - a Swedish Lymphoma Register Study.

BACKGROUND & PURPOSE: The COVID-19 pandemic posed a large challenge for healthcare systems across the world. Comprehensive data on the impact of the COVID-19 pandemic on incidence and mortality in lymphoma are lacking. PATIENTS/METHODS: Using data from the Swedish lymphoma register, we compare incidence and 1-year survival of lymphoma patients in Sweden before (2017-2019) and during the pandemic (2020 and 2021). RESULTS: Fewer patients were diagnosed with lymphomas during March-June 2020, but the annual incidence rates for 2020 and 2021 were similar to those of 2017-2019. A larger proportion of patients presented with stage IV disease during 2021. There were no differences in other base-line characteristics nor application of active treatment in pre-pandemic and pandemic years. One-year overall survival was not inferior among lymphoma patients during the pandemic years compared to pre-pandemic years i.e., 2017-2019. INTERPRETATION: The COVID-19 pandemic had limited impact on the incidence and mortality of lymphoma in Sweden.

Preservation of the celiac branch of the vagus nerve reduces the incidence of postoperative diarrhea in gastric cancer: a cohort study.

BACKGROUND: To investigate the short-term and long-term outcomes of preserving the celiac branch of the vagus nerve during laparoscopic distal gastrectomy. METHODS: A total of 149 patients with prospective diagnosis of gastric cancer who underwent laparoscopic-assisted distal gastrectomy (LADG) combined with Billroth-II anastomosis and D2 lymph node dissection between 2017 and 2018 were retrospectively analyzed. The patients were divided into the preserved LADG group (P-LADG, n = 56) and the resected LADG group (R-LADG, n = 93) according to whether the vagus nerve celiac branch was preserved. We selected 56 patients (P-LADG, n = 56) with preservation of the celiac branch of the vagus nerve and 56 patients (R-LADG, n = 56) with removal of the celiac branch of the vagus nerve by propensity-matched score method. Postoperative nutritional status, weight change, short-term and long-term postoperative complications, and gallstone formation were evaluated in both groups at 5 years of postoperative follow-up. The status of residual gastritis and bile reflux was assessed endoscopically at 12 months postoperatively. RESULTS: The incidence of diarrhea at 5 years postoperatively was lower in the P-LADG group than in the R-LADG group (p < 0.05). In the multivariate logistic analysis, the removal of vagus nerve celiac branch was an independent risk factor for the occurrence of postoperative diarrhea (odds ratio = 3.389, 95% confidential interval = 1.143-10.049, p = 0.028). In the multivariate logistic analysis, the removal of vagus nerve celiac branch was an independent risk factor for the occurrence of postoperative diarrhea (odds ratio = 4.371, 95% confidential interval = 1.418-13.479, p = 0.010). CONCLUSIONS: Preservation of the celiac branch of the vagus nerve in LADG reduced the incidence of postoperative diarrhea postoperatively in gastric cancer. TRIAL REGISTRATION: This study was registered with the Ethics Committee of the First Affiliated Hospital of Dalian Medical University in 2014 under the registration number: LCKY2014-04(X).

Occupational accidents in Slovak Military Forests and Estates: incidence, timing, and trends over 10 years.

Introduction: Forestry provides a wide range of employment opportunities worldwide and is seen as one of the high-risk industries in terms of occupational accidents. Objectives: The submitted study analyzed the injury rate in the Military Forests and Estates of the Slovak Republic (62.6 thousand ha) between 2013 and 2022. Methods: The data analyses included regression and correlation analyses, χ2 tests to analyze the relationships between studied variables, and incidence rates. Results: During the observed period, employees suffered 26 occupational accidents, of which 19.2% were light, 57.7% were registered, 23.1% were severe, and 0% were fatal. For every 1 million m3 of harvested timber, 7.7 accidents occurred. The incidence rate during the observed period was 672.1/100,000 employees. The highest proportion of accidents was in the age group 51-60 years and in employees with the lowest length of work experience <5 years. Regarding time, the highest proportion of occupational accidents occurred between 8:01 and 10:00 AM (53.8%) and day-wise on Thursdays (46.2%). The highest proportion of accidents occurred among forest workers (65.3%) during pruning and silviculture activities (42.3%). The most common injury site was forest stands (65.3%). Superficial injuries (34.6%) were the most common, mainly affecting the lower limbs (50%). The most frequent material agents causing the accidents were work and transport areas as sources of worker fall (38.5%), and the most frequent reason for an accident to occur was the lack of personal requirements for proper work performance (92.4%), whereas only (3.8%) of accidents occurred due to the use of forbidden or hazardous working procedures. Conclusion: The presented study identified the most vulnerable worker groups and provided an overview of the overall injury rate at the state forest company in Slovakia. The documentation can be incorporated into the safety strategies of forest enterprises.

Incidence of mental disorders in soldiers deployed to Afghanistan who have or have not experienced a life-threatening military incident-a quasi-experimental cohort study.

Introduction: There is very good international research on deployment-related mental disorders in military personnel. The incidence rates show a very wide range. A new strategy is therefore proposed in order to achieve better standardization and thus better comparability of the studies. In addition to a non-deployed comparison group, we propose to compare deployed soldiers with and without critical military incidents during the deployment. This additional distinction makes it possible to differentiate between the influencing variables of actual threat and general deployment stress. Methods: N = 358 male combat soldiers deployed to Afghanistan were included in the study. Clinical interviews were conducted several days before deployment and after deployment. Of them, n = 80 soldiers suffered a life-threatening military incident during deployment, whereas 278 soldiers did not. Odds ratios (OR) were calculated for the groups with and without critical military incidents and the new onset for PTSD, anxiety disorders and depressive disorders. Results: When comparing both groups, we found significantly higher 1-year incidence rates in the group with critical military incidents: 6.4% vs. 1.1% (OR 6.2) for post-traumatic stress disorder (PTSD); 7.0% vs. 1.1% (OR 6.5) for depression; and 15.9% vs. 2.8% (OR 6.6) for anxiety disorders. The 1-year incidence rate of mental multimorbidity (PTSD with anxiety or depression) was 4.8% vs. 0.4% (OR 12.0). Discussion: These results indicate that life-threatening military incidents during military deployment are important to mental health. As the different threat levels of the various missions are taken into account, additional predictors could be determined more precisely in further research.

Incidence and predictors of mortality among neonates admitted with birth asphyxia to neonatal intensive care unit of West Shewa Zone Public Hospitals, Central Ethiopia.

BACKGROUND: Birth asphyxia is still one of the primary causes of newborn mortality worldwide. Similarly, the risk of newborn asphyxia in Ethiopia remains unacceptably high. Thus, studies on the incidence and predictors of mortality among newborns admitted with birth asphyxia are crucial to addressing this problem. As a result, the purpose of this study was to assess the incidence and predictors of mortality among neonates admitted with birth asphyxia to the neonatal intensive care units (NICUs) of West Shewa Zone Public Hospitals in Central Ethiopia. METHODS: An institution-based retrospective cohort study was conducted among 760 asphyxiated neonates admitted to the NICUs of West Shewa Zone Public Hospitals between 30 March 2021 and 30 April 2023. The data were collected using CSEntry and analysed bu using Stata V.17. Bivariate and multivariate Cox proportional hazard regression analyses were carried out, and significant predictors were found using a 95% CI and a p<0.05. RESULTS: A total of 760 asphyxiated neonates were followed for a total of 6880 neonatal days. At the end of follow-up, 263 (34.6%) of the neonates died (95% CI 31.3% to 38.1%), which resulted in a mortality incidence of 10.6/100 person-days of observation. Chewing khat (adjusted HR, AHR 2.21; 95% CI 1.13 to 4.31), home delivery (AHR 1.45, 95% CI 1.1 to 1.9), lack of antenatal care follow-up (AHR 1.44, 95% CI 1.08 to 1.89), hypothermia (AHR 1.56, 95% CI 1.12 to 2.17), hypoglycaemia (AHR 2.23, 95% CI 1.91 to 2.25) and obstructed labour (AHR 1.4, 95% CI 1.02 to 1.91) were found to be the significant predictors of neonatal mortality among asphyxiated neonates at a p≤0.05. CONCLUSION AND RECOMMENDATION: The magnitude of neonatal mortality among asphyxiated neonates in the study area was high. Therefore, in order to significantly reduce the risks of birth asphyxia and subsequent newborn death, all interested stakeholders should take these predictors into consideration.

Real-World Evidence of the Impact of a Novel Surgical Irrigant on Surgical Site Infections in Primary Total Knee Arthroplasty Performed at an Ambulatory Surgery Center.

Background: Total knee arthroplasty (TKA) is one of the most common inpatient and outpatient surgical procedures performed in the United States and is predicted to increase 401% by 2040. Surgical site infections (SSIs) at an incidence rate of approximately 2% are costly post-operative complications in TKA. Intra-operative surgical irrigants are used to decrease contaminating microbial bioburden within the surgical site to prevent SSI. The primary objective of this retrospective study was to evaluate the impact of a novel surgical irrigant called XPERIENCE® Advanced Surgical Irrigation (XP; Next Science, Jacksonville, FL) on SSI incidence in primary TKA performed at an ambulatory surgery center (ASC). Patients and Methods: Primary TKAs were performed at a free-standing ASC. The novel surgical irrigant was used intra-operatively to rinse away debris and micro-organisms from the surgical site. Retrospective data collation included SSI rates, complication rates, and re-admissions due to SSI within 90 days of index surgery. Results: Among the 524 primary TKA surgeries, one peri-prosthetic joint infection (PJI) was diagnosed within 90 days of index surgery and one superficial incisional SSI was diagnosed within 30 days of index surgery. The PJI was attributed to an exogenously acquired upper respiratory tract infection rather than due to the failure of intra-operative regimes. The 0.19% PJI incidence rate indicated significant efficacy of XP in decreasing PJI. An overall complication rate of 7.82% was noted with none of the complications associated with usage of the novel surgical irrigant. Conclusions: XPERIENCE is a promising intra-operative antimicrobial irrigant that can be easily incorporated into a broader infection prevention strategy.

Trends and geospatial distribution of stillbirths in Uganda, 2014-2020.

INTRODUCTION: Uganda with 17.8 stillbirths per 1,000 deliveries in 2021, is among the countries with a high burden of stillbirths globally. In 2014, Uganda adopted the World Health Organization Every New-born Action Plan (ENAP), which targets < 10 stillbirths per 1,000 deliveries by 2035. Little is known about the trends of stillbirth burden since ENAP was introduced. We assessed the temporal, and spatial distribution of stillbirths, in Uganda, 2014-2020, to inform programming for safe pregnancies and deliveries. METHODS: We obtained and analysed stillbirth surveillance data from the District Health Information System, 2014-2020. A stillbirth was defined as the death of a foetus > 28 weeks of pregnancy or weighing > 1000 g before or during birth and reported to a health facility. We calculated annual incidence rates of stillbirths per 1,000 deliveries at district, regional, and national levels. We used logistic regression to determine the significance of trends. RESULTS: The overall national annual incidence of stillbirths decreased from 24/1,000 deliveries in 2014 to 17/1,000 deliveries in 2020. During the same period, reporting rates declined from 71% in 2014 to 46% in 2020. The central region continuously had the highest incidence rate for the past 5 years despite the largest decline (OR = 0.79; CI = 0.77-0.83, P < 0.001) while the eastern region had the smallest decline (OR = 0.59; CI = 0.57-0.61, P < 0.001). Districts with persistently high annual incidence rates of stillbirths (> 30/1000) included Mubende, Kalangala, Hoima, and Nebbi. There was no difference in the reporting rates of the most- vs. least-affected districts. CONCLUSION: Even with suboptimal reporting, the incidence of stillbirths remained above the national target. Specific areas in the country appear to have particularly high stillbirth rates. We recommend continuous capacity building in managing pregnant women with an emphasis on the most affected districts, and investigation into the reasons for low reporting.

Incidence of sick leave and disability pension in adults with musculoskeletal pain and co-occurring long-term conditions: data from the Norwegian HUNT study and national registries.

BACKGROUND: Musculoskeletal pain is one of the leading causes of work productivity loss. Long-term conditions (LTCs) commonly occur alongside musculoskeletal pain. However, the incidence of sick leave and disability pension according to LTC status in people with musculoskeletal pain has not been previously described. METHODS: Working-age participants (20-65 years) with persistent musculoskeletal pain who participated in the HUNT3 Study (1995-97) were included. Twenty-five LTCs were classified into 8 LTC groups according to the International Classification of Diseases version 11. Data on sickness and disability benefits were obtained from the National Insurance Database and linked to the HUNT3 data using participants' personal identification number. Age-adjusted incidence rates (IRs) (per 10,000 person-years) and hazard ratios (HRs) of sick leave during 5-year follow-up and disability pension during ~ 25-year follow-up were estimated with 95% confidence intervals (CIs) and presented according to LTC status. RESULTS: Overall, 11,080 participants with musculoskeletal pain were included. Of those, 32% reported one LTC and 45% reported ≥ 2 LTCs. During the follow up period, 1,312 participants (12%) received disability pension due to musculoskeletal conditions. The IR of sick leave and disability pension due to musculoskeletal conditions increased with number of LTCs. Specifically, the IR of sick leave was 720 (95% CI 672 to 768) in participants without any LTCs and 968 (95% CI 927 to 1,009) if they had ≥ 2 LTCs. The IRs of disability pension were 87 (95% CI 75 to 98) and 167 (95% CI 154 to 179) among those with no LTCs and ≥ 2 LTCs, respectively. The incidence of sick leave and disability pension due to musculoskeletal conditions was largely similar across LTCs, although the incidence of disability pension was somewhat higher among people with sleep disorders (IR: 223, 95% CI 194 to 252). CONCLUSIONS: Among people with persistent musculoskeletal pain, the incidence of prematurely leaving the work force due to musculoskeletal conditions was twice as high for those with multiple LTCs compared to those without any LTCs. This was largely irrespective of the type of LTC, indicating that the number of LTCs are an important feature when evaluating work participation among people with musculoskeletal pain.

High incidence of imperforate vagina in ADGRA3-deficient mice.

BACKGROUND: Ten percent of the female population suffers from congenital abnormalities of the vagina, uterus, or oviducts, with severe consequences for reproductive and psychological health. Yet, the underlying causes of most of these malformations remain largely unknown. ADGRA3 (GPR125) is involved in WNT signaling and planar cell polarity, mechanisms vital to female reproductive tract development. Although ADGRA3 is a well-established spermatogonial stem cell marker, its role within the female urogenital system remains unclear. RESULTS: In this study, we found Adgra3 to be expressed throughout the murine female urogenital system, with higher expression pre-puberty than after sexual maturation. We generated a global Adgra3-/- mouse line and observed imperforate vagina in 44% of Adgra3-/- females, resulting in distension of the reproductive tract and infertility. Ovarian morphology, plasma estradiol, ovarian Cyp19a1, and vaginal estrogen receptor α (Esr1) expression were unaffected. However, compared to controls, a significantly lower bone mineral density was found in Adgra3-/- mice. Whereas vaginal opening in mice is an estrogen-dependent process, 17ß-estradiol treatment failed to induce vaginal canalization in Adgra3-/- mice. Furthermore, a marked reduction in vaginal and ovarian progesterone receptor expression was observed concomitant with an upregulation of apoptotic regulators Bcl2, Bid, and Bmf in adult Adgra3-/- females with a closed vagina. CONCLUSIONS: Our collective results shed new insights into the complex mechanisms by which the adhesion receptor ADGRA3 regulates distal vaginal tissue remodeling during vaginal canalization via altered sex hormone responsiveness and balance in apoptotic regulators. This highlights the potential of ADGRA3 as a target in diagnostic screening and/or therapy for obstructive vaginal malformations in humans.