Bone Anchor Fixation in the Repair of Blunt Traumatic Abdominal Wall Hernias: A Western Trauma Association Multicenter Study.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWHs) are rare but require a variety of operative techniques to repair including bone anchor fixation (BAF) when tissue tears off bony structures. This study aimed to provide a descriptive analysis of BAF technique for blunt TAWH repair. Bone anchor fixation and no BAF repairs were compared, hypothesizing increased hernia recurrence with BAF repair. METHODS: A secondary analysis of the WTA blunt TAWH multicenter study was performed including all patients who underwent repair of their TAWH. Patients with BAF were compared to those with no BAF with bivariate analyses. RESULTS: 176 patients underwent repair of their TAWH with 41 (23.3%) undergoing BAF. 26 (63.4%) patients had tissue fixed to bone, with 7 of those reinforced with mesh. The remaining 15 (36.6%) patients had bridging mesh anchored to bone. The BAF group had a similar age, sex, body mass index, and injury severity score compared to the no BAF group. The time to repair (1 vs 1 days, P = .158), rate of hernia recurrence (9.8% vs 12.7%, P = .786), and surgical site infection (SSI) (12.5% vs 15.6%, P = .823) were all similar between cohorts. CONCLUSIONS: This largest series to date found nearly one-quarter of TAWH repairs required BAF. Bone anchor fixation repairs had a similar rate of hernia recurrence and SSI compared to no BAF repairs, suggesting this is a reasonable option for repair of TAWH. However, future prospective studies are needed to compare specific BAF techniques and evaluate long-term outcomes including patient-centered outcomes such as pain and quality of life.

Aorto-left atrial fistula secondary to aortic infective endocarditis in a dog with a bicuspid aortic valve.

An 11-year-old male neutered English Bulldog was presented for evaluation of thrombocytopenia, acute onset of ataxia, and vomiting. A new murmur was auscultated on physical examination. Transthoracic echocardiographic examination revealed a bicuspid aortic valve, vegetative lesions on the aortic valve, and continuous shunting from the aortic root to the left atrium through an aorta to left atrial fistula. The dog was euthanized due to guarded prognosis and critical condition. Pathological examination confirmed presence of bicuspid aortic valve, aorto-left atrial fistula, and aortic infective endocarditis. Antemortem blood culture revealed two unusual organisms: Achromobacter xylosoxidans and Fusobacterium mortiferum.

The impact of anticoagulant medications on fragility femur fracture care: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study.

INTRODUCTION: Due to their hypocoagulable state on presentation, anticoagulated patients with femoral fragility fractures typically experience delays to surgery. There are no large, multicentre studies previously carried out within the United Kingdom (UK) evaluating the impact of anticoagulant use in this patient population. This study aimed to evaluate the current epidemiology and compare the perioperative management of anticoagulated and non-anticoagulated femoral fragility fracture patients. METHODS: Data was prospectively collected through a collaborative, multicentre approach involving hospitals across the United Kingdom. Femoral fragility fracture patients aged ≥60 years and admitted to hospital between 1st May to 31st July 2023 were included. Main outcomes under investigation included time to surgery, receipt of blood transfusion between admission and 48 h following surgery, length of stay, and 30-day mortality. These were assessed using multivariable linear and logistic regression, and Cox proportional hazards models. Only data from hospitals ≥90 % case ascertainment with reference to figures from the National Hip Fracture Database (NHFD) were analysed. RESULTS: Data on 10,197 patients from 78 hospitals were analysed. 18.5 % of patients were taking anticoagulants. Compared to non-anticoagulated patients, time to surgery was longer by 7.59 h (95 %CI 4.83-10.36; p < 0.001). 42.41 % of anticoagulated patients received surgery within 36 h (OR 0.54, 95 %CI 0.48-0.60, p < 0.001). Differences in time to surgery were similar between countries however there was some variation across units. There were no differences in blood transfusion and length of stay between groups (OR 1.03, 95 %CI 0.88-1.22, p = 0.646 and 0.22 days, 95 %CI -0.45-0.89; p = 0.887 respectively). Mortality within 30 days of admission was higher in anticoagulated patients (HR 1.27, 95 %CI 1.03-1.57, p = 0.026). CONCLUSIONS: Anticoagulated femoral fragility fracture patients comprise a substantial number of patients, and experience relatively longer delays to surgery with less than half receiving surgery within 36 h of admission. This may have resulted in their comparatively higher mortality rate. Inclusion of anticoagulation status in the minimum data set for the NHFD to enable routine auditing of performance, and development of a national guideline on the management of this growing and emerging patient group is likely to help standardise practice in this area and improve outcomes.

Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

A western trauma association multicenter comparison of mesh versus non-mesh repair of blunt traumatic abdominal wall hernias.

BACKGROUND: Blunt traumatic abdominal wall hernias (TAWH) occur in <1 % of trauma patients. Optimal repair techniques, such as mesh reinforcement, have not been studied in detail. We hypothesize that mesh use will be associated with increased surgical site infections (SSI) and not improve hernia recurrence. MATERIALS AND METHODS: A secondary analysis of the Western Trauma Association blunt TAWH multicenter study was performed. Patients who underwent TAWH repair during initial hospitalization (1/2012-12/2018) were included. Mesh repair patients were compared to primary repair patients (non-mesh). A logistic regression was conducted to assess risk factors for SSI. RESULTS: 157 patients underwent TAWH repair during index hospitalization with 51 (32.5 %) having mesh repair: 24 (45.3 %) synthetic and 29 (54.7 %) biologic. Mesh patients were more commonly smokers (43.1 % vs. 22.9 %, p = 0.016) and had a larger defect size (10 vs. 6 cm, p = 0.003). Mesh patients had a higher rate of SSI (25.5 % vs. 9.5 %, p = 0.016) compared to non-mesh patients, but a similar rate of recurrence (13.7 % vs. 10.5%, p = 0.742), hospital length of stay (LOS), and mortality. Mesh use (OR 3.66) and higher ISS (OR 1.06) were significant risk factors for SSI in a multivariable model. CONCLUSION: Mesh was used more frequently in flank TAWH and those with a larger defect size. Mesh use was associated with a higher incidence and risk of SSI but did not reduce the risk of hernia recurrence. When repairing TAWH mesh should be employed judiciously, and prospective randomized studies are needed to identify clear indications for mesh use in TAWH.

Comparative diagnoses of respiratory disease in preweaned dairy calves using sequential thoracic ultrasonography and clinical respiratory scoring.

AIMS: Bovine respiratory disease (BRD) has serious impacts on dairy production and animal welfare. It is most commonly diagnosed based on clinical respiratory signs (CRS), but in recent years, thoracic ultrasonography (TUS) has emerged as a diagnostic tool with improved sensitivity and specificity. This study aimed to assess the alignment of BRD diagnoses based on a Clinical Respiratory Scoring Chart (CRSC) and weekly TUS findings throughout the progression of BRD of variable severity in preweaned Holstein dairy heifers. METHODS: A total of 60 calves on two farms were followed from the 2nd week of life through the 11th week of life and assessed on a weekly basis for CRS and lung consolidation via TUS. The alignment of BRD diagnoses based on CRSC scores and TUS findings was evaluated across disease progression (pre-consolidation, onset, chronic, or recovered) and severity (lobular or lobar lung consolidation) using receiver operator curves and area under the curves combined with Cohen's kappa (κ), sensitivity, and specificity. RESULTS: The diagnosis of BRD using CRSC scores ≥5 aligned best with the onset of lobar lung consolidation (>1 cm in width and full thickness). This equated to an acceptable level of discrimination (AUC = 0.76), fair agreement (κ = 0.37), and a sensitivity of 29% and specificity of 99%. Similarly, there was acceptable discrimination (AUC = 0.70) and fair agreement (κ = 0.33) between CRSC ≥5 and the onset of a less severe threshold of disease based on lobular (1-3 cm2 but not full thickness) or lobar consolidation. Discrimination remained acceptable (AUC = 0.71) with fair agreement (κ = 0.28) between CRSC scores ≥2 for nasal discharge and/or cough (spontaneous or induced) and the onset of lobar consolidation. However, sensitivity was <40% across comparisons and outside of the onset of disease there tended to be poor discrimination, slight agreement, and lowered sensitivity between CRS and TUS diagnoses of lobular or lobar consolidation (pre-consolidation, chronic, or recovered). Conversely, specificity was relatively high (≥92%) across comparisons suggesting that CRSC diagnoses indicative of BRD and associated lung consolidation tend to result in few false positive diagnoses and accurate identification of healthy animals. CONCLUSIONS AND CLINICAL RELEVANCE: Although we found the specificity of clinical signs for diagnosing lung consolidation to be ≥92% across all methods of TUS evaluations, the low levels of sensitivity dictate that clinical assessments lead to many false negative diagnoses. Consequently, depending on clinical signs alone to diagnose BRD within populations of dairy calves will likely result in overlooking a substantial proportion of subclinically affected animals that could inform the success of treatment and prevention protocols and guide management decisions.

Transforming Parkinson's Care in Africa (TraPCAf): protocol for a multimethodology National Institute for Health and Care Research Global Health Research Group project.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and, according to the Global Burden of Disease estimates in 2015, was the fastest growing neurological disorder globally with respect to associated prevalence, disability, and deaths. Information regarding the awareness, diagnosis, phenotypic characteristics, epidemiology, prevalence, risk factors, treatment, economic impact and lived experiences of people with PD from the African perspective is relatively sparse in contrast to the developed world, and much remains to be learned from, and about, the continent. METHODS: Transforming Parkinson's Care in Africa (TraPCAf) is a multi-faceted, mixed-methods, multi-national research grant. The study design includes multiple sub-studies, combining observational (qualitative and quantitative) approaches for the epidemiological, clinical, risk factor and lived experience components, as appropriate, and interventional methods (clinical trial component). The aim of TraPCAf is to describe and gain a better understanding of the current situation of PD in Africa. The countries included in this National Institute for Health and Care Research (NIHR) Global Health Research Group (Egypt, Ethiopia, Ghana, Kenya, Nigeria, South Africa and Tanzania) represent diverse African geographies and genetic profiles, with differing resources, healthcare systems, health and social protection schemes, and policies. The research team is composed of experts in the field with vast experience in PD, jointly led by a UK-based and Africa-based investigator. DISCUSSION: Despite the increasing prevalence of PD globally, robust data on the disease from Africa are lacking. Existing data point towards the poor awareness of PD and other neurological disorders on the continent and subsequent challenges with stigma, and limited access to affordable services and medication. This multi-site study will be the first of its kind in Africa. The data collected across the proposed sub-studies will provide novel and conclusive insights into the situation of PD. The selected country sites will allow for useful comparisons and make results relevant to other low- and middle-income countries. This grant is timely, as global recognition of PD and the public health challenge it poses builds. The work will contribute to broader initiatives, including the World Health Organization's Intersectoral global action plan on epilepsy and other neurological disorders. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN77014546 .

A qualitative evaluation of internet information on hip and knee osteoarthritis.

BACKGROUND: Hip and knee arthritis are two of the most common conditions that result in referral to orthopaedic outpatient clinics. Many patients now use the internet to research their condition and to inform their decision about treatment options. This has implications for the process of informed consent. AIM: To assess the quality of patient information on the internet regarding hip and knee arthritis. METHODS: 'Hip arthritis' and 'Knee arthritis' were entered as search terms into a popular search engine. To adjust for temporal variation, the process was repeated one month and one year later. Of the 200 results analysed, 83 websites met the inclusion criteria. The quality of patient information presented on these websites was assessed using a validated scoring instrument by two independent observers. RESULTS: Most websites assessed were of poor quality; nearly half of all websites did not mention any risks or complications associated with surgical intervention for these conditions. CONCLUSIONS: As part of their professional obligation to provide a robust process of informed consent, clinicians should be aware of the variable quality of patient information available on the internet. As such, they should be prepared to advise their patients about quality websites where reliable information can be sought.

The effect of surgical complications on long-term prognosis following oesophagectomy.

INTRODUCTION: Complications are frequent after oesophagectomy, and there is evidence these adversely impact long-term prognosis. However, the effect of multiple complications, and the absolute magnitude of effect on survival is unclear. This study aimed to examine these effects in a single high-volume UK unit. METHODS: Patients undergoing oesophagectomy for cancer and who survived to 90 days post-oesophagectomy were analysed. Complications were graded according to the Clavien-Dindo (CD) classification and the Comprehensive Complication Index (CCI). The effect and magnitude of effect of complications on survival were assessed using multivariable cox regression and the risk-adjusted population attributable fraction. RESULTS: In total, 380 patients were included. Complications occurred in 251 (66.1%). Suffering ≥3 complications (HR 1.89, 95%CI 1.13-3.16, p = 0.015) or an unplanned escalation in care (HR 2.22, 95%CI 1.43-3.45, p < 0.001) significantly reduced survival whereas pulmonary complications and anastomotic leak did not. Patients with a CCI>30 had worse overall survival (HR 1.91, 95%CI 1.32-2.76, p < 0.001) and CCI>30 due to multiple minor complications gave a worse prognosis compared to CCI>30 due to major complications (HR 2.44, 95%CI 1.14-5.20, p = 0.022). An estimated 9.1% (95%CI 3.4-14.4%) of deaths at 5 years were attributable to a CCI>30. CONCLUSION: Long-term survival following oesophagectomy for cancer is significantly affected by complications and the cumulative effect of multiple complications. Interestingly, multiple minor complications had a worse effect on survival than major complications. The absolute magnitude of effect is substantial: minimising all types of postoperative complications could have significant benefit to overall outcomes.

A ring-like accretion structure in M87 connecting its black hole and jet.

The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.

Oxygen Evolution/Reduction Reaction Catalysts: From In Situ Monitoring and Reaction Mechanisms to Rational Design.

The oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are core steps of various energy conversion and storage systems. However, their sluggish reaction kinetics, i.e., the demanding multielectron transfer processes, still render OER/ORR catalysts less efficient for practical applications. Moreover, the complexity of the catalyst-electrolyte interface makes a comprehensive understanding of the intrinsic OER/ORR mechanisms challenging. Fortunately, recent advances of in situ/operando characterization techniques have facilitated the kinetic monitoring of catalysts under reaction conditions. Here we provide selected highlights of recent in situ/operando mechanistic studies of OER/ORR catalysts with the main emphasis placed on heterogeneous systems (primarily discussing first-row transition metals which operate under basic conditions), followed by a brief outlook on molecular catalysts. Key sections in this review are focused on determination of the true active species, identification of the active sites, and monitoring of the reactive intermediates. For in-depth insights into the above factors, a short overview of the metrics for accurate characterizations of OER/ORR catalysts is provided. A combination of the obtained time-resolved reaction information and reliable activity data will then guide the rational design of new catalysts. Strategies such as optimizing the restructuring process as well as overcoming the adsorption-energy scaling relations will be discussed. Finally, pending current challenges and prospects toward the understanding and development of efficient heterogeneous catalysts and selected homogeneous catalysts are presented.

EffEctiveness of Prophylactic fOam dressings in the prevention of saCral pressure injuries in at-risk hospitalised patients: the EEPOC trial.

BACKGROUND: Prophylactic dressings are increasingly used to prevent pressure injuries in hospitalised patients. However, evidence regarding the effectiveness of these dressings is still emerging. This trial aims to determine the clinical and cost-effectiveness of a prophylactic silicone foam border dressing in preventing sacral pressure injuries in medical-surgical patients. METHODS: This is a multicentre, pragmatic, parallel group, randomised controlled trial. A sample size of 1320 was calculated to have >90% power to detect a 5% difference in the primary outcome at an alpha of 0.05. Adult patients admitted to participating medical-surgical wards are screened for eligibility: ≥18 years, admitted to hospital within the previous 36 h, expected length of stay of ≥24 h, and assessed high risk for hospital-acquired pressure injury. Consenting participants are randomly allocated to either prophylactic silicone foam dressing intervention or usual care without any dressing as the control group via a web-based randomisation service independent of the trial. Patients are enrolled across three Australian hospitals. The primary outcome is the cumulative incidence of patients who develop a sacral pressure injury. Secondary outcomes include the time to sacral pressure injury, incidence of severity (stage) of sacral pressure injury, cost-effectiveness of dressings, and process evaluation. Participant outcomes are assessed daily for up to 14 days by blinded independent outcome assessors using de-identified, digitally modified sacral photographs. Those who develop a sacral pressure injury are followed for an additional 14 days to estimate costs of pressure injury treatment. Analysis of clinical outcomes will be based on intention-to-treat, per-protocol, and sensitivity analyses. DISCUSSION: This trial aims to provide definitive evidence on the effect prophylactic dressings have on the development of hospital-acquired sacral pressure injuries in medical-surgical patients. A parallel economic evaluation of pressure injury prevention and treatment will enable evidence-informed decisions and policy. The inclusion of a process evaluation will help to explain the contextual factors that may have a bearing on trial results including the acceptability of the dressings to patients and staff. The trial commenced 5 March 2020 and has been significantly delayed due to COVID-19. TRIAL REGISTRATION: ANZCTR ACTRN12619000763145. Prospectively registered on 22 May 2019.

Risk factors for recurrence in blunt traumatic abdominal wall hernias: A secondary analysis of a Western Trauma association multicenter study.

BACKGROUND: Few studies have investigated risk factors for recurrence of blunt traumatic abdominal wall hernias (TAWH). METHODS: Twenty trauma centers identified repaired TAWH from January 2012 to December 2018. Logistic regression was used to investigate risk factors for recurrence. RESULTS: TAWH were repaired in 175 patients with 21 (12.0%) known recurrences. No difference was found in location, defect size, or median time to repair between the recurrence and non-recurrence groups. Mesh use was not protective of recurrence. Female sex, injury severity score (ISS), emergency laparotomy (EL), and bowel resection were associated with hernia recurrence. Bowel resection remained significant in a multivariable model. CONCLUSION: Female sex, ISS, EL, and bowel resection were identified as risk factors for hernia recurrence. Mesh use and time to repair were not associated with recurrence. Surgeons should be mindful of these risk factors but could attempt acute repair in the setting of appropriate physiologic parameters.

Long-term impact of early non-infectious complications at the initiation of peritoneal dialysis.

BACKGROUND: Early non-infectious complications at initiation of peritoneal dialysis (PD) are a major burden with unknown long-term impacts on individuals. METHODS: Prospective multicentre cohort study using univariable and multivariable Cox regression to identity mortality risk and PD discontinuation risk in those with and without non-infectious complications. All individuals commencing PD between 1 January 2014 and 31 December 2018, registered in the New Zealand Peritoneal Dialysis Registry (NZPDR) were followed up to 31 December 2020. Early non-infectious complications defined as functional, catheter-related, exit-site dialysate leak or anatomical leak complications occurring within 30 days of initiation of PD. Primary outcomes were patient survival and time on PD therapy. Secondary outcomes were peritonitis free survival, first PD catheter survival and catheter tunnel infection free survival. RESULTS: Of 1596 individuals included in the study, 102 experienced an early non-infectious complication. Multivariable analysis demonstrated these complications were associated with higher risk of overall mortality (hazard ratio (HR) 1.71; 95% confidence interval (CI) 1.21-2.44), PD discontinuation (HR 1.84; 95% CI 1.41-2.41) and first catheter failure (HR 2.89; 95% CI 2.28-3.66). No difference was found for risk of development of first peritonitis episode or catheter tunnel infection. Mortality risk was associated with functional and exit-site dialysate leak complications and continued beyond 180 days. Risk of PD discontinuation and first catheter loss were associated with catheter and functional complications in the first 180 days. CONCLUSION: Early non-infectious complications are associated with long-term mortality risk. Further research in risk factors and causes of early non-infectious complications are required.

Clinical outcomes following surgical management of insertional Achilles tendinopathy using a double-row suture bridge technique with mean two-year follow-up.

BACKGROUND: The clinical outcomes following surgical management of insertional Achilles tendinopathy (IAT) vary depending on the surgical technique used to reattach the Achilles tendon following debridement. The aim of this study was to investigate the clinical outcomes of patients with IAT who underwent surgical management with a double-row suture bridge technique used to reattach the Achilles tendon. METHODS: A retrospective review of consecutive patients diagnosed with IAT, who underwent surgical management utilising a double-row suture bridge technique (Arthex Speedbridge), and a minimum of 3-month follow-up were included. The primary outcome was the Manchester-Oxford Foot Questionnaire (MOXFQ) Index score which is a patient reported outcome measure (PROM). Secondary outcomes included EuroQol EQ-5D-5L health-related quality of life PROM and complication rates. RESULTS: Between July 2013 and June 2020, 50 consecutive patients (23 male; 27 female) were included. The mean age (± standard deviation) was 52.3 ± 11.3 (range 29.0-84.3). Pre- and post-operative PROM data were available for all cases. The mean follow-up was 2.4 ± 1.9 years. The MOXFQ Index score improved from 48.5 to 12.4 (p < 0.01), EQ-5D-5L improved from 2.7 ± 0.46 to 1.2 ± 0.37 (p < 0.01), and EQ-VAS improved from 48.0 ± 18.4 to 84.1 ± 12.6 (p < 0.01). Four patients had complications which were of minimal clinical relevance and caused no deviation from routine recovery. There were no cases of tendon rupture. CONCLUSION: This study has demonstrated that surgical management of IAT is safe and effective with clinical improvement in both clinical and general health-related quality of life outcome PROMs. LEVEL OF EVIDENCE: IV.

Robotic-assisted laparoscopic colposuspension for female stress urinary incontinence: a prospective series.

The suspension of use of sub-urethral mesh in the UK in 2018 has seen the resurgence of colposuspension in female SUI surgery. Open and laparoscopic colposuspension techniques are well recognised. We present data from 28 robotic-assisted laparoscopic colposuspension (RALCp) procedures, reporting on technique, safety and efficacy. Approval was obtained from the hospital New and Novel Procedures Committee. All patients had urodynamic assessment prior to surgery. Data was prospectively gathered and 24-h pad usage and Urinary Incontinence Short Form Questionnaire (ICIQ-UI-SF) scores were used to assess symptom severity and quality of life. PGII scores were used to assess patient satisfaction after the procedure. Paired T test analysis was conducted. Since May 2019, robotic colposuspension has been performed in 28 patients. The mean age and BMI were 49 and 27 (kg/m2), respectively, with a mean follow-up period of 12 months. 67.9% of patients had pure urodynamic SUI and 32.1% of patients had previous anti-SUI surgery. Average operating time was 127 min, blood loss 20 ml and length of stay 2 days. There was a significant 73% improvement in mean 24-h pad usage (p = 0.001) and an improvement in mean ICIQ-UI-SF scores from 18.1 to 9.4 (p = 0.0001). Day 1 mean pain score was 5/10. This is the largest series of its kind. Robotic colposuspension is safe and feasible with significant improvements seen in quality of life scores and number of pads used per day. It presents a minimally invasive treatment option in female SUI, however needs larger volume evaluation and longer follow-up for further evaluation.

Studies of mutations of assembly factor Hit1 in budding yeast suggest translation defects as the molecular basis for PEHO syndrome.

Regulation of protein synthesis is critical for control of gene expression in all cells. Ribosomes are ribonucleoprotein machines responsible for translating cellular proteins. Defects in ribosome production, function, or regulation are detrimental to the cell and cause human diseases, such as progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome. PEHO syndrome is a devastating neurodevelopmental disorder caused by mutations in the ZNHIT3 gene, which encodes an evolutionarily conserved nuclear protein. The precise mechanisms by which ZNHIT3 mutations lead to PEHO syndrome are currently unclear. Studies of the human zinc finger HIT-type containing protein 3 homolog in budding yeast (Hit1) revealed that this protein is critical for formation of small nucleolar ribonucleoprotein complexes that are required for rRNA processing and 2'-O-methylation. Here, we use budding yeast as a model system to reveal the basis for the molecular pathogenesis of PEHO syndrome. We show that missense mutations modeling those found in PEHO syndrome patients cause a decrease in steady-state Hit1 protein levels, a significant reduction of box C/D snoRNA levels, and subsequent defects in rRNA processing and altered cellular translation. Using RiboMethSeq analysis of rRNAs isolated from actively translating ribosomes, we reveal site-specific changes in the rRNA modification pattern of PEHO syndrome mutant yeast cells. Our data suggest that PEHO syndrome is a ribosomopathy and reveal potential new aspects of the molecular basis of this disease in translation dysregulation.