Phosphodiesterase 4D activity in acrodysostosis-associated neural pathology: too much or too little?

Members of the phosphodiesterase 4 (PDE4) enzyme family regulate the availability of the secondary messenger cyclic adenosine monophosphate (cAMP) and, by doing so, control cellular processes in health and disease. In particular, PDE4D has been associated with Alzheimer's disease and the intellectual disability seen in fragile X syndrome. Furthermore, single point mutations in critical PDE4D regions cause acrodysostosis type 2(ACRDYS2, also referred to as inactivating PTH/PTHrP signalling disorder 5 or iPPSD5), where intellectual disability is seen in ∼90% of patients alongside the skeletal dysmorphologies that are characteristic of acrodysostosis type 1 (ACRDYS1/iPPSD4) and ACRDYS2. Two contrasting mechanisms have been proposed to explain how mutations in PDE4D cause iPPSD5. The first mechanism, the 'over-activation hypothesis', suggests that cAMP/PKA (cyclic adenosine monophosphate/protein kinase A) signalling is reduced by the overactivity of mutant PDE4D, whilst the second, the 'over-compensation hypothesis' suggests that mutations reduce PDE4D activity. That reduction in activity is proposed to cause an increase in cellular cAMP, triggering the overexpression of other PDE isoforms. The resulting over-compensation then reduces cellular cAMP and the levels of cAMP/PKA signalling. However, neither of these proposed mechanisms accounts for the fine control of PDE activation and localization, which are likely to play a role in the development of iPPSD5. This review will draw together our understanding of the role of PDE4D in iPPSD5 and present a novel perspective on possible mechanisms of disease.

Validation of a novel professional automated auscultatory upper-arm cuff blood pressure monitor in a general population according to the AAMI/ESH/ISO Universal Standard: KOROT V2 Doctor (InBody BPBIO280KV).

OBJECTIVE: A novel automated auscultatory upper arm cuff blood pressure (BP) monitor KOROT V2 Doctor (InBody BPBIO280KV) was developed for professional use. An electronic stethoscope embedded in the device cuff records the Korotkoff sounds, which are graphically displayed during deflation allowing visual evaluation by the healthcare professional. The device provides automated measurements of BP and this study evaluated its accuracy. METHODS: The requirements of the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018) and its Amendment 1.2020-01 were applied. Participants were recruited to fulfill the age, sex, BP, arm circumference, and cuff distribution criteria of the Universal Standard and its Amendment in a general population using the same arm sequential measurement method. Three cuffs of the test device were tested for arm circumference 23-28, 28-35, and 33-42 cm. RESULTS: Data from 85 individuals were analyzed [mean age: 56.4 ±â€…16.0 (SD) years, 50 men, arm circumference 23-42 cm]. For validation Criterion 1, the mean difference ±SD between the test device and reference BP readings (N = 255) was -1.3 ± 6.0/1.5 ± 5.0 mmHg (systolic/diastolic; threshold ≤5 ±â€…8 mmHg). For Criterion 2, the SD of the averaged BP differences per individual (N = 85) was 4.61/3.48 mmHg (systolic/diastolic; threshold ≤6.82/6.78 mmHg). CONCLUSION: The KOROT V2 Doctor (InBody BPBIO280KV) device for professional use, which provides automated auscultatory measurements with visual display of the Korotkoff sounds, comfortably fulfills all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in a general population and can be recommended for clinical use.

Polyamine Catabolism Revisited: Acetylpolyamine Oxidase Plays a Minor Role due to Low Expression.

Biogenic polyamines are ubiquitous compounds. Dysregulation of their metabolism is associated with the development of various pathologies, including cancer, hyperproliferative diseases, and infections. The canonical pathway of polyamine catabolism includes acetylation of spermine and spermidine and subsequent acetylpolyamine oxidase (PAOX)-mediated oxidation of acetylpolyamines (back-conversion) or their direct efflux from the cell. PAOX is considered to catalyze a non-rate-limiting catabolic step. Here, we show that PAOX transcription levels are extremely low in various tumor- and non-tumor cell lines and, in most cases, do not change in response to altered polyamine metabolism. Its enzymatic activity is undetectable in the majority of cell lines except for neuroblastoma and low passage glioblastoma cell lines. Treatment of A549 cells with N1,N11-diethylnorspermine leads to PAOX induction, but its contribution to polyamine catabolism remains moderate. We also describe two alternative enzyme isoforms and show that isoform 4 has diminished oxidase activity and isoform 2 is inactive. PAOX overexpression correlates with the resistance of cancer cells to genotoxic antitumor drugs, indicating that PAOX may be a useful therapeutic target. Finally, PAOX is dispensable for the replication of various viruses. These data suggest that a decrease in polyamine levels is achieved predominantly by the secretion of acetylated spermine and spermidine rather than by back-conversion.

Charting the importance of filamin A posttranslational modifications.

Filamin A is an essential protein in the cell cytoskeleton because of its actin binding properties and unique homodimer rod-shaped structure, which organises actin into three-dimensional orthogonal networks imperative to cell motility, spreading and adhesion. Filamin A is subject to extensive posttranslational modification (PTM) which serves to co-ordinate cellular architecture and to modulate its large protein-protein interaction network which is key to the protein's role as a cellular signalling hub. Characterised PTMs include phosphorylation, irreversible cleavage, ubiquitin mediated degradation, hydroxylation and O-GlcNAcylation, with preliminary evidence of tyrosylation, carbonylation and acetylation. Each modification and its relation to filamin A function will be described here. These modifications are often aberrantly applied in a range of diseases including, but not limited to, cancer, cardiovascular disease and neurological disease and we discuss the concept of target specific PTMs with novel therapeutic modalities. In summary, our review represents a topical 'one-stop-shop' that enables understanding of filamin A function in cell homeostasis and provides insight into how a variety of modifications add an extra level of Filamin A control.

Hospital charges for laparoscopic sleeve gastrectomy compared to robotic sleeve gastrectomy: a multicenter study.

BACKGROUND: Sleeve gastrectomy has become a gold standard in addressing medically refractory obesity. Robotic platforms are becoming more utilized, however, data on its cost-effectiveness compared to laparoscopy remain controversial (1-3). At NYU Langone Health, many of the bariatric surgeons adopted robotic surgery as part of their practices starting in 2021. We present a retrospective cost analysis of laparoscopic sleeve gastrectomy (LSG) vs. robotic sleeve gastrectomy (RSG) at New York University (NYU) Langone Health campuses. METHODS: All adult patients ages 18-65 who underwent LSG or RSG from 202 to 2023 at NYU Langone Health campuses (Manhattan, Long Island, and Brooklyn) were evaluated via electronic medical records and MBSAQIP 30-day follow-up data. Patients with prior bariatric surgery were excluded. Complication-related ICD-10/CPT codes are collected and readmission costs will be estimated from ICD codes using the lower limit of CMS transparent NYU standard charges (3). Direct charge data for surgery and length of stay cost data were also obtained. Statistical T-test and chi-squared analysis were used to compare groups. RESULTS: Direct operating cost data at NYU Health Campuses demonstrated RSG was associated with 4% higher total charges, due to higher OR charges, robotic-specific supplies, and more post-op ED visits. CONCLUSIONS: RSG was associated with higher overall hospital charges compared to LSG, though there are multiple contributing factors. More research is needed to identify cost saving measures. This study is retrospective in nature, and does not include indirect costs nor reimbursement. Direct operating costs, per contractual agreement with suppliers, are only given as percentages. Data are limited to 30-day follow-up.

Malaria Tropica: An Autopsy Case Report With a Discussion on the Presence of Malaria in Bulgaria.

Malaria is an infectious disease caused by several types of parasitic plasmodia and transmitted to humans through Anopheles mosquitoes. The disease has long been widespread and has caused a significant number of deaths and decreased life quality from sequelae worldwide. As understanding of the disease increased immensely at the beginning of the 20th century, eradication plans were implemented to decrease disease transmission. This led to the successful eradication of malaria across predominantly industrialized countries, with multiple geographic areas remaining malaria endemic zones to this day. With climate changes and migration, the risk of reintroduction of malaria to malaria-free zones has risen due to relatively easy travel to endemic zones and importation of cases. On the one hand, this is a significant public health risk and, on the other, a challenge to the medical system, as healthcare workers in malaria-free zones are often ill-prepared to recognize, diagnose, and treat malaria cases. Herein, we present an autopsy and histopathology case report of tropical (falciparum) malaria, complicated with blackwater fever (malignant malaria) with prevalent gross and histopathological changes, including hemomelanin deposition in the spline, liver, and bone marrow; visible parasitic forms in the remaining red blood cells; Durk's granulomas, sludge, and petechial hemorrhages in the central nervous system; and hemoglobin casts within the renal tubular structures. We also discuss the history and risk of reintroducing malaria into a malaria-free zone - Bulgaria.

Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals.

AIMS: Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited. METHODS AND RESULTS: Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan-Meier event rates for the primary endpoint representing a composite of nonfatal myocardial infarction, nonfatal stroke (ischemic or hemorrhagic), nonfatal heart failure hospitalization or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) meta-analysis and published evidence on BP-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan (I) and 17.6% for ramipril (R). These rates were only modestly better than that observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of Irbesartan + Amlodipine (ARR = 8.7% compared to untreated) and 14.3% for Ramipril + Amlodipine (ARR = 8.0% compared to untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with ASCVD and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in diabetics and 7.8% in those without diabetes. CONCLUSION: This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.

Visible fluid motion on manipulation as the new threshold for intraoperatively determined knee arthroplasty component loosening: A Delphi study.

PURPOSE: There is a lack of a clear, uniform definition for intraoperatively assessed component loosening of a knee arthroplasty component, complicating the interpretation and interchangeability of results of diagnostic studies using an intraoperative observation as the reference test. The purpose of this study was to establish a consensus among specialised knee revision surgeons regarding the definition of intraoperatively determined loosening of total or unicondylar knee arthroplasty components. METHODS: Utilising the Delphi consensus method, an international panel of highly specialised knee revision surgeons was invited to participate in a three-round process. The initiation of the first round involved the exploration of possible criteria for intraoperatively determined loosening with open questions. The second round focused on rating these criteria importance on a five-point Likert scale. For the third round, criteria that reached consensus were summarised in consecutive definitions for intraoperatively determined loosening and proposed to the panel. Consensus was established when over 70% of participants agreed with a definition for intraoperatively determined loosening. RESULTS: The 34 responding panel members described in total 60 different criteria in the first round of which 34 criteria received consensus in the second round. Summarising these criteria resulted in four different definitions as minimal requirements for intraoperatively determined loosening. Eighty-eight percent of the panel members agreed on defining a component as loose if there is visible fluid motion at the interface observed during specific movements or when gently applying direct force. CONCLUSION: This study successfully established a consensus using a Delphi method among knee revision surgeons on the definition of intraoperatively determined component loosening. By agreeing on the visibility of fluid motion as new definition, this study provides a standardised reference for future diagnostic research. This definition will enhance the interpretability and interchangeability of future diagnostic studies evaluating knee arthroplasty component loosening. LEVEL OF EVIDENCE: Level V.

Urinary Bladder Nephrogenic Adenoma: A Histopathological Case Report.

Nephrogenic adenomas are benign lesions that develop within the urinary tract. Most often developing within the urinary bladder, these lesions have a debatable etiopathogenesis, with hamartoma, rest hyperplasia, and transplantation of renal tubular cells being the most widely accepted ones. Nephrogenic adenomas develop more often in adult males, and predisposing factors for their development are prior urinary system injury, infection, or malignancy, with a subset of cases developing in renal transplant patients. Herein, we present a case of a male patient in his seventies who initially presented to our institution with urinary disturbances and was subsequently diagnosed with low-grade, non-invasive urothelial carcinoma. After treatment, the patient remained disease-free for a period of seven calendar years. The current presentation was due to dysuria, and bladder endoscopy revealed a ureteral stricture and two small exophytic lesions neighboring the location of the previously treated urothelial carcinoma. Histology revealed complex papillary architecture and cystic spaces lined by a monolayer of monomorphous epithelial cells with foci of hobnail appearance. The papillary stroma consisted of edematous fibrous tissue with hyperemic blood vessels and focal infiltration by inflammatory cells. Based on the histological findings, the diagnosis of nephrogenic adenoma was established.

Association of Sleep Quality and General, Mental, and Oral Health with Lifestyle Traits (Dietary Intake, Smoking Status) in Arthritis: A Cross-Sectional Study from the Canadian Community Health Survey (CCHS).

Arthritis is associated with health challenges. Lifestyle traits are believed to influence arthritis development and progression; however, data to support personalized treatment regimens based on holistic lifestyle factors are missing. This study aims to provide a comprehensive list of associations between lifestyle traits and the health status of individuals with arthritis in the Canadian population, using binary logistic regression analysis on data from the Canadian Community Health Survey, which includes 104,359 respondents. Firstly, we explored the association between arthritis and various aspects of health status including self-reported lifestyle factors. Secondly, we examined the associations between self-reported dietary intake and smoking status with general, mental, and oral health, and sleep disturbance among individuals both with and without arthritis. Our analysis revealed that individuals with arthritis reported considerably poorer general, mental, and oral health, and poorer sleep quality compared to those without arthritis. Associations were also found between self-reported dietary intake and various measures of health status in individuals with arthritis. Smoking and exposure to passive smoking were associated not only with arthritis but also with compromised sleep quality and poorer general, mental, and oral health in people with and without arthritis. This study highlights the need for personalized and holistic approaches that may include a combination of dietary interventions, oral health improvements, sleep therapies, and smoking cessation for improved arthritis prevention and care.

Detection of the benzodiazepine bromazolam by liquid chromatography with quadrupole time of flight mass spectrometry in postmortem toxicology casework and prevalence in Indiana (2023).

For the past 60 years, benzodiazepines such as chlordiazepoxide, diazepam, and alprazolam have been used as pharmaceutical medications for the treatment of myriad conditions including anxiety, seizures, and insomnia. In more recent years, novel benzodiazepine derivatives have emerged as illicit substances in powders and counterfeit tablets on the illicit drug market. In 2016, bromazolam, a brominated derivative of alprazolam, emerged on the illicit drug market in Europe, but the substance was not reported in the USA until 2019-2020. In this study, we report the emergence and subsequent prevalence of bromazolam in postmortem blood in the state of Indiana during 2023. Analysis was completed by a solvent protein precipitation extraction with acetonitrile and detection by liquid chromatography with quadrupole time of flight mass spectrometry. During 2023, bromazolam was detected in 94 cases across 25 counties in Indiana. It was never the sole substance detected and was commonly detected alongside fentanyl (83 cases), norfentanyl (77 cases), 4-anilino-N-phenethylpiperidine (76 cases), acetylfentanyl (49 cases), methamphetamine (32 cases), naloxone (25 cases), 11-nor-9-carboxy-tetrahydrocannabinol (24 cases), and benzoylecgonine (20 cases). After official query with the Indiana Department of Health, it was found that bromazolam was specifically included in the cause of death certification in 31 fatalities (32.9%). Due to the scarcity of information regarding this novel benzodiazepine derivative in postmortem toxicology and its involvement in fatalities, it is important that forensic toxicology laboratories consider adding bromazolam to their comprehensive scope of analysis.

Bacterial community and cyanotoxin gene distribution of the Winam Gulf, Lake Victoria, Kenya.

The Winam Gulf (Kenya) is frequently impaired by cyanobacterial harmful algal blooms (cHABs) due to inadequate wastewater treatment and excess agricultural nutrient input. While phytoplankton in Lake Victoria have been characterized using morphological criteria, our aim is to identify potential toxin-producing cyanobacteria using molecular approaches. The Gulf was sampled over two successive summer seasons, and 16S and 18S ribosomal RNA gene sequencing was performed. Additionally, key genes involved in production of cyanotoxins were examined by quantitative PCR. Bacterial communities were spatially variable, forming distinct clusters in line with regions of the Gulf. Taxa associated with diazotrophy were dominant near Homa Bay. On the eastern side, samples exhibited elevated cyrA abundances, indicating genetic capability of cylindrospermopsin synthesis. Indeed, near the Nyando River mouth in 2022, cyrA exceeded 10 million copies L-1 where there were more than 6000 Cylindrospermopsis spp. cells mL-1. In contrast, the southwestern region had elevated mcyE gene (microcystin synthesis) detections near Homa Bay where Microcystis and Dolichospermum spp. were observed. These findings show that within a relatively small embayment, composition and toxin synthesis potential of cHABs can vary dramatically. This underscores the need for multifaceted management approaches and frequent cyanotoxin monitoring to reduce human health impacts.

Preferences and perceptions of 617 migraine patients on acute and preventive migraine treatment attributes and clinical trial endpoints.

BACKGROUND: To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important. DESIGN AND METHODS: The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used. RESULTS: Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment. Conclusion: Listening to patients' needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.

Methods of identifying surgical Necrotizing Enterocolitis-a systematic review and meta-analysis.

BACKGROUND: Current data suggests potential benefit of earlier surgery for necrotizing enterocolitis (NEC) however this requires accurate prognostication early in the disease course. This study aims to identify and determine the effectiveness of previously reported methods or tests for the identification of surgical NEC. METHODS: Systematic review and meta-analysis with registration on PROSPERO including articles describing a method of identifying surgical NEC. Outcomes of interest were effectiveness and repeatability of index test. RESULTS: Of the 190 full-text articles screened, 90 studies were included which contained 114 methods of identifying surgical NEC in 9546 infants. Of these methods, 44 were a scoring system, 37 a single biomarker, 24 an imaging method, and 9 an invasive method. Sensitivity and specificity ranged from 12.8-100% to 13-100%, respectively. Some methods (9.6%) provided insufficient methods for repeatability within clinical practice or research. Meta-analyses were possible for only 2 methods, the metabolic derangement 7 score and abdominal ultrasound. CONCLUSIONS: A range of methods for identifying surgical NEC have been identified with varying overall performance and uncertainties about reproducibility and superiority of any method. External validation in large multicentre datasets should allow direct comparison of accuracy and prospective study should evaluate impact on clinical outcomes. IMPACT: Earlier identification of need for surgery in necrotizing enterocolitis (NEC) has the potential to improve the unfavourable outcomes in this condition. As such, many methods have been developed and reported to allow earlier identification of surgical NEC. This study is the first synthesis of the literature which identifies previously reported methods and the effectiveness of these. Many methods, including scoring systems and biomarkers, appear effective for prognostication in NEC and external validation is now required in multicentre datasets prior to clinical utility.

Effects of an 11-week vibro-tactile stimulation treatment on voice symptoms in laryngeal dystonia.

Background: Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common therapeutic option for patients with LD involves Botulinum neurotoxin injections. Objective: Provide empirical evidence that non-invasive vibro-tactile stimulation (VTS) of the skin over the voice box can provide symptom relief to those affected by LD. Methods: Single-group 11-week randomized controlled trial with a crossover between two dosages (20 min of VTS once or 3 times per week) self-administered in-home in two 4-week blocks. Acute effects of VTS on voice and speech were assessed in-lab at weeks 1, 6 and 11. Participants were randomized to receive either 40 Hz or 100 Hz VTS. Main outcome measures: Primary: smoothed cepstral peak prominence (CPPS) of the voice signal to quantify voice and speech abnormalities, and perceived speech effort (PSE) ranked by participants as a measure of voice effort (scale 1-10). Secondary: number of voice breaks during continuous speech, the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) inventory as a measure of overall disease severity and the Voice Handicap Index 30-item self report. Results: Thirty-nine people with a confirmed diagnosis of adductor-type LD (mean [SD] age, 60.3 [11.3] years; 18 women and 21 men) completed the study. A single application of VTS improved voice quality (median CPPS increase: 0.41 dB, 95% CI [0.20, 0.61]) and/or reduced voice effort (PSE) by at least 30% in up to 57% of participants across the three study visits. Effects lasted from less than 30 min to several days. There was no effect of dosage and no evidence that the acute therapeutic effects of VTS increased or decreased longitudinally over the 11-week study period. Both 100 and 40 Hz VTS induced measurable improvements in voice quality and speech effort. VTS induced an additional benefit to those receiving Botulinum toxin. Participants, not receiving Botulinum treatment also responded to VTS. Conclusion: This study provides the first systematic empirical evidence that the prolonged use of laryngeal VTS can induce repeatable acute improvements in voice quality and reductions of voice effort in LD. Clinical trial registration: ClinicalTrials.gov ID: NCT03746509.

The recent disappearance of a persistent Planktothrix bloom: Characterization of a regime shift in the phytoplankton of Sandusky Bay (USA).

Sandusky Bay is the drowned mouth of the Sandusky River in the southwestern portion of Lake Erie. The bay is a popular recreation location and a regional source for drinking water. Like the western basin of Lake Erie, Sandusky Bay is known for being host to summer cyanobacterial harmful algal blooms (cHABs) year after year, fueled by runoff from the predominantly agricultural watershed and internal loading of legacy nutrients (primarily phosphorus). Since at least 2003, Sandusky Bay has harbored a microcystin-producing bloom of Planktothrix agardhii, a species of filamentous cyanobacteria that thrives in low light conditions. Long-term sampling (2003-2018) of Sandusky Bay revealed regular Planktothrix-dominated blooms during the summer months, but in recent years (2019-2022), 16S rRNA gene community profiling revealed that Planktothrix has largely disappeared. From 2017-2022, microcystin decreased well below the World Health Organization (WHO) guidelines. Spring TN:TP ratios increased in years following dam removal, yet there were no statistically significant shifts in other physicochemical variables, such as water temperature and water clarity. With the exception of the high bloom of Planktothrix in 2018, there was no statistical difference in chlorophyll during all other years. Concurrent with the disappearance of Planktothrix, Cyanobium spp. have become the dominant cyanobacterial group. The appearance of other potential toxigenic genera (i.e., Aphanizomenon, Dolichospermum, Cylindrospermopsis) may motivate monitoring of new toxins of concern in Sandusky Bay. Here, we document the regime shift in the cyanobacterial community and propose evidence supporting the hypothesis that the decline in the Planktothrix bloom was linked to the removal of an upstream dam on the Sandusky River.

How to salvage the fractured coracoid during the Latarjet Procedure? An empirical approach.

The Latarjet procedure is a frequently used stabilization procedure in case of anterior shoulder instability with critical glenoid bone loss and/or off-track Hill Sachs lesions. Although uncommon, intra-operative graft fractures do occur. When confronted with this potentially challenging intra-operative complication, having a secondary solution is paramount to achieve a successful outcome. This technical note provides a treatment algorithm that may function as a useful guideline to assist surgeons that experience this potentially complex unintended event during a Latarjet procedure. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

An In-Vitro Comparison of Mixed Reality Navigation to Traditional Freehand and Patient Specific Instrumentation Techniques for Glenoid Guide Pin Insertion during Shoulder Arthroplasty.

BACKGROUND: Accurate insertion of the glenoid guide pin in shoulder arthroplasty (RSA) is important for obtaining optimized glenoid component position and orientation. The objective of this study was to evaluate and compare the accuracy of three glenoid guide pin insertion techniques: 1) traditional software planning using freehand guide pin insertion (freehand), 2) guide pin insertion utilizing patient-specific instrumentation (PSI), and 3) using a mixed reality navigation (MR-NAV) system. METHODS: Twenty (20) computer tomography (CT) scans were obtained from patients exhibiting glenoid erosion patterns according to the Walch and Favard classifications. Cases were planned using validated three-dimensional (3D) preoperative planning software. The CT data was then used to 3D print triplicate plastic models of each glenoid to evaluate the three guide pin insertion techniques. The first technique employed traditional software planning with freehand guide pin insertion. The second method used preoperatively planned PSI guides, while the third utilized a MR-NAV system, which provided real-time holographic guidance during guide pin insertion. Once all guide pins had been inserted into the models, an independent optical tracking system and custom digitization device was used to quantify the position and orientation of each guide pin relative to the glenoid. The outcomes for this study included the absolute mean error in guide pin inclination, version, and entry point relative to the preoperative plan. The absolute Total Global Error was also assessed, which was defined as the sum of the absolute guide pin orientation and position error relative to the preoperative plan. RESULTS: No statistically significant differences between MR-NAV and PSI were found for the inclination error (2±1° versus 2±1°; P=0.056), version error (1±1° versus 1±1°; P=1.000), and Total Global Error (5±1 [mm+deg] versus 5±1 [mm+deg], P=1.000), respectively. The freehand technique produced significantly greater error than MR-NAV and PSI for inclination (5±3°, P≤0.017), version (4±3°, P≤0.032) and Total Global Error (8±3 [mm+deg], P<0.001). No statistically significant differences in the entry point error were observed between all guide pin insertion methods (P≥0.058). DISCUSSION: These results demonstrate that the precision and accuracy of MR-NAV is comparable to PSI and superior to a freehand technique for glenoid guide pin insertion in-vitro. Further study is needed to compare the accuracy of these techniques intra-operatively, in addition to assessing a potential learning curve between surgeons of varying experience with the MR-NAV system.

Hemoglobin and Its Relationship with Fatigue in Long-COVID Patients Three to Six Months after SARS-CoV-2 Infection.

Background: While some long-term effects of COVID-19 are respiratory in nature, a non-respiratory effect gaining attention has been a decline in hemoglobin, potentially mediated by inflammatory processes. In this study, we examined the correlations between hemoglobin levels and inflammatory biomarkers and evaluated the association between hemoglobin and fatigue in a cohort of Long-COVID patients. Methods: This prospective cohort study in the Netherlands evaluated 95 (mostly hospitalized) patients, aged 40-65 years, 3-6 months post SARS-CoV-2 infection, examining their venous hemoglobin concentration, anemia (hemoglobin < 7.5 mmol/L in women and <8.5 mmol/L in men), inflammatory blood biomarkers, average FSS (Fatigue Severity Score), demographics, and clinical features. Follow-up hemoglobin was compared against hemoglobin during acute infection. Spearman correlation was used for assessing the relationship between hemoglobin concentrations and inflammatory biomarkers, and the association between hemoglobin and fatigue was examined using logistic regression. Results: In total, 11 (16.4%) participants were suffering from anemia 3-6 months after SARS-CoV-2 infection. The mean hemoglobin value increased by 0.3 mmol/L 3-6 months after infection compared to the hemoglobin during the acute phase (p-value = 0.003). Whilst logistic regression showed that a 1 mmol/L greater increase in hemoglobin is related to a decrease in experiencing fatigue in Long-COVID patients (adjusted OR 0.38 [95%CI 0.13-1.09]), we observed no correlations between hemoglobin and any of the inflammatory biomarkers examined. Conclusion: Our results indicate that hemoglobin impairment might play a role in developing Long-COVID fatigue. Further investigation is necessary to identify the precise mechanism causing hemoglobin alteration in these patients.