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Thyroid hormones are released from thyroglobulin (Tg) in lysosomes, which are impaired in infantile/nephropathic cystinosis. Cystinosis is a lysosomal cystine storage disease due to defective cystine exporter, cystinosin. Cystinotic children develop subclinical and then overt hypothyroidism. Why hypothyroidism is the most frequent and earliest endocrine complication of cystinosis is unknown. We here defined early alterations in Ctns(-/-) mice thyroid and identified subcellular and molecular mechanisms. At 9 months, T4 and T3 plasma levels were normal and TSH was moderately increased (∼4-fold). By histology, hyperplasia and hypertrophy of most follicles preceded colloid exhaustion. Increased immunolabeling for thyrocyte proliferation and apoptotic shedding indicated accelerated cell turnover. Electron microscopy revealed endoplasmic reticulum (ER) dilation, apical lamellipodia indicating macropinocytic colloid uptake, and lysosomal cystine crystals. Tg accumulation in dilated ER contrasted with mRNA down-regulation. Increased expression of ER chaperones, glucose-regulated protein of 78 kDa and protein disulfide isomerase, associated with alternative X-box binding protein-1 splicing, revealed unfolded protein response (UPR) activation by ER stress. Decreased Tg mRNA and ER stress suggested reduced Tg synthesis. Coordinated increase of UPR markers, activating transcription factor-4 and C/EBP homologous protein, linked ER stress to apoptosis. Hormonogenic cathepsins were not altered, but lysosome-associated membrane protein-1 immunolabeling disclosed enlarged vesicles containing iodo-Tg and impaired lysosomal fusion. Isopycnic fractionation showed iodo-Tg accumulation in denser lysosomes, suggesting defective lysosomal processing and hormone release. In conclusion, Ctns(-/-) mice showed the following alterations: 1) compensated primary hypothyroidism and accelerated thyrocyte turnover; 2) impaired Tg production linked to ER stress/UPR response; and 3) altered endolysosomal trafficking and iodo-Tg processing. The Ctns(-/-) thyroid is useful to study disease progression and evaluate novel therapies.

Thyroid hormones are released from thyroglobulin (Tg) in lysosomes, which are impaired in infantile/nephropathic cystinosis. Cystinosis is a lysosomal cystine storage disease due to defective cystine exporter, cystinosin. Cystinotic children develop subclinical and then overt hypothyroidism. Why hypothyroidism is the most frequent and earliest endocrine complication of cystinosis is unknown. We here defined early alterations in Ctns(-/-) mice thyroid and identified subcellular and molecular mechanisms. At 9 months, T4 and T3 plasma levels were normal and TSH was moderately increased (∼4-fold). By histology, hyperplasia and hypertrophy of most follicles preceded colloid exhaustion. Increased immunolabeling for thyrocyte proliferation and apoptotic shedding indicated accelerated cell turnover. Electron microscopy revealed endoplasmic reticulum (ER) dilation, apical lamellipodia indicating macropinocytic colloid uptake, and lysosomal cystine crystals. Tg accumulation in dilated ER contrasted with mRNA down-regulation. Increased expression of ER chaperones, glucose-regulated protein of 78 kDa and protein disulfide isomerase, associated with alternative X-box binding protein-1 splicing, revealed unfolded protein response (UPR) activation by ER stress. Decreased Tg mRNA and ER stress suggested reduced Tg synthesis. Coordinated increase of UPR markers, activating transcription factor-4 and C/EBP homologous protein, linked ER stress to apoptosis. Hormonogenic cathepsins were not altered, but lysosome-associated membrane protein-1 immunolabeling disclosed enlarged vesicles containing iodo-Tg and impaired lysosomal fusion. Isopycnic fractionation showed iodo-Tg accumulation in denser lysosomes, suggesting defective lysosomal processing and hormone release. In conclusion, Ctns(-/-) mice showed the following alterations: 1) compensated primary hypothyroidism and accelerated thyrocyte turnover; 2) impaired Tg production linked to ER stress/UPR response; and 3) altered endolysosomal trafficking and iodo-Tg processing. The Ctns(-/-) thyroid is useful to study disease progression and evaluate novel therapies.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies. However, surgical morbidity is high, and prediction of severe postoperative complications (SPC) is limited. We hypothesized that the changes in thromboelastogram (TEG) values following CRS could be associated with SPC.

This study aims to develop physician support software for determining ovulation time and assess its impact on pregnancy outcomes in natural cycle frozen embryo transfers (NC-FET). To develop, assess, and validate an ovulation prediction model, three datasets were used: REI Ovulation Determination dataset (500 cycles) split into training (309), validation (90), and test (101) sets; the Documented Ovulation dataset (101 cycles) with confirmed ovulation (documented follicular rupture and LH surge); and the Clinical Pregnancy Rates dataset (515 NC-FET cycles), categorized into "Matched" and "Mismatched" based on alignment with the model's ovulation determination. Pregnancy outcomes were compared between the groups. The ovulation prediction model exhibited 93.85% and 92.89% matching rates with the REI Ovulation Determination and Documented Ovulation datasets, respectively. In the Clinical Pregnancy Rates dataset, the Matched group (282 cycles) showed significantly higher clinical pregnancy rates than the Mismatched group (34.6% vs. 25.9%, p = 0.04) and similar results for patients under 37 (41.1% vs. 30.7%, p = 0.04). Logistic regression indicated lower pregnancy rates in Mismatched cases (odds ratio 0.67 for the general population, 0.63 for patients under 37). In conclusion, we introduce a highly accurate AI ovulation prediction model. Treatment cycles aligning with the model's recommendations had significantly increased clinical pregnancy rates., Competing Interests: Declarations. Competing interests: Competing Interests: Authors: Ettie Maman, Rohi Hourvitz, Almog Luz, Micha Baum, and Ariel Hourvitz are shareholders and board members of FertilAI LTD. Authors Eden Moran, Nevo Itzhak and Shachar Reuvenny are FertilAI employees. Author Michal Youngster has nothing to declare. Authers’ contribution. Almog Luz -Conception and design, acquisition of data, analysis and interpretation of data, drafting the article and revising, approval of the version to be published, agree to be accountable for all aspects of the work. Ariel Hourvitz - Conception and design, analysis and interpretation of data, revising the article, approval of the version to be published, agree to be accountable for all aspects of the work. Eden Moran - Conception and design, analysis and interpretation of data, approval of the version to be published, agree to be accountable for all aspects of the work. Nevo Itzhak - Conception and design, acquisition of data, analysis and interpretation of data, drafting the article and revising, approval of the version to be published, agree to be accountable for all aspects of the work. Shachar Reuvenny - Conception and design, analysis and interpretation of data, approval of the version to be published, agree to be accountable for all aspects of the work. Rohi Hourvitz - Conception and design, analysis and interpretation of data, approval of the version to be published, agree to be accountable for all aspects of the work. Michal Youngster - Conception and design, analysis and interpretation of data, revising the article, approval of the version to be published, agreet o be accountable for all aspects of the work. Micha Baum - Conception and design, analysis and interpretation of data, revising the article, approval of the version to be published, agree to be accountable for all aspects of the work. Ettie Maman - Conception and design,, analysis and interpretation of data, drafting the article and revising, approval of the version to be published, agree to be accountable for all aspects of the work., (© 2024. The Author(s).)

Purpose: To evaluate the efficacy of subconjunctival tranexamic acid (TXA) in reducing intraoperative bleeding, shortening surgery duration, and improving postoperative outcomes in pterygium surgery. Methods: In this double-blind, randomized controlled trial, 50 eyes of 50 patients undergoing pterygium surgery were randomly assigned to receive either subconjunctival injection of 0.25 mL of 5% TXA (TXA group, n = 25) or an equivalent volume of saline (control group, n = 25). Baseline characteristics, including age, gender, working environment, allergies, preoperative logMAR best-corrected visual acuity, and systemic anticoagulant or antiplatelet therapy, were similar between the groups. The primary outcome measures were intraoperative bleeding, surgery duration, and the number of eye spears used. Secondary outcome measures included postoperative visual acuity and pterygium recurrence rates at 3 years post-surgery. Results: No significant differences were observed between the TXA group and the control group in terms of surgery duration (445.3 ± 94.8 s vs. 423.5 ± 80.6 s, P = 0.40), the number of eye spears used (3.5 ± 2.4 vs. 3.5 ± 2.6, P = 0.97), or the weight of absorbed blood (1.94 ± 1.40 grams vs. 1.90 ± 1.25 grams, P = 0.91). Additionally, there were no significant differences in postoperative visual acuity (0.14 ± 0.13 logMAR vs. 0.20 ± 0.19 logMAR, P = 0.39) or pterygium recurrence rates at 3 years post-surgery (8.0% vs. 4.4%, P = 0.60). Subconjunctival TXA injection was safe, with no reported adverse events or complications associated with its use. Conclusion: Subconjunctival injection of TXA did not significantly reduce intraoperative bleeding, shorten surgery duration, or improve postoperative outcomes in pterygium surgery. The intervention was safe and well-tolerated, but further research is warranted to explore alternative interventions or modifications to the surgical technique that may improve outcomes in pterygium surgery.

Litter decomposition is expected to be positively associated with precipitation despite evidence that decomposers of varying sizes have different moisture dependencies. We hypothesized that higher tolerance of macro-decomposers to aridity may counterbalance the effect of smaller decomposers, leading to similar decomposition rates across climatic gradients. We tested this hypothesis by placing plant litter baskets of different mesh sizes in seven sites along a sharp precipitation gradient, and by characterizing the macro-decomposer assemblages using pitfall trapping. We found that decomposers responded differently to precipitation levels based on their size. Microbial decomposition increased with precipitation in the winter while macro-decomposition peaked in arid sites during the summer. This led to similar overall decomposition rates across the gradient except in hyper-arid sites. Macro-decomposer richness, abundance, and biomass peaked in arid environments. Our findings highlight the importance of macro-decomposition in arid-lands, possibly resolving the dryland decomposition conundrum, and emphasizing the need to contemplate decomposer size when investigating zoogeochemical processes., Competing Interests: VT, NS, JD, YH, EG, DH No competing interests declared, (© 2024, Torsekar, Sagi et al.)

Objective: The Blackchin Guitarfish Glaucostegus cemiculus is endemic to the Mediterranean Sea and is critically endangered, but relevant routine laboratory data are unavailable. Our objectives were to determine the packed cell volume (PCV), comprehensive serum chemistry analytes, and serum total thyroxine (sTT4) concentration; compare serum albumin and serum globulin concentrations as measured by two different methods; and describe the blood cell morphology of healthy, free-ranging Blackchin Guitarfish., Methods: Wild Blackchin Guitarfish were captured using a seine net. Blood samples for serum chemistry and hematological analyses were obtained and measured using routine laboratory methods. The fish were tagged and released., Result: This study included 43 Blackchin Guitarfish (17 males and 26 females) that were younger than 6 months as estimated based on total length and body weight. The median PCV (n = 23) was 22% (minimum-maximum [min-max] = 15-25%). Median sTT4 (n = 10) measured by chemiluminescence immunoassay was 7.86 nmol/L (min-max = 7.52-9.57 nmol/L). The study included a comprehensive, 25-analyte serum chemistry analysis (e.g., serum iron and unbound and total iron-binding capacity) and a morphological description of all blood cells. Serum electrophoresis (SEP; n = 13) yielded a consistent serum albumin-migrating protein fraction and four globulin fractions. Serum electrophoretograms corroborating these results are presented., Conclusion: In Blackchin Guitarfish, the serum albumin-migrating fraction measured by SEP combined with serum total protein concentration yields a much higher albumin concentration compared to that measured by bromocresol green spectrophotometry. The true identity of this albumin-migrating fraction remains to be identified. The analytes' calculated 2.5-97.5% interpercentile intervals should be considered as reference intervals applying to Blackchin Guitarfish of similar age but should be applied cautiously to adult fish., (© 2024 American Fisheries Society.)

The interaction between formic acid (FA) and water (W) holds significant importance in various chemical processes. Our study combines vacuum-ultraviolet photoionization mass spectrometry with density functional calculations to investigate formic acid water clusters generated in supersonic molecular beams. The mass spectra obtained reveal the formation of protonated clusters as the major product. Enhanced intensities are observed in the mass spectra for a number of clusters holding the following composition, FA 1 W 5 H + , FA 2 W 4 H + , FA 3 W 3 H + , FA 4 W 2 H + , FA 5 W 1 H + and FA 6 W 2 H + compared to their neighbors with one less or one more water component. Our calculations shed light on these potentially stable structures, highlighting cyclic arrangements with molecules enclosed within the ring as the most stable structures, and demonstrate a decrease in the stability upon the addition of a water molecule. Comparing experimental appearance energies with calculated ionization energies suggests that fragmentation can occur from clusters of various sizes.

Objective: Develop a new method for continuous prediction that utilizes a single temporal pattern ending with an event of interest and its multiple instances detected in the temporal data., Methods: Use temporal abstraction to transform time series, instantaneous events, and time intervals into a uniform representation using symbolic time intervals (STIs). Introduce a new approach to event prediction using a single time intervals-related pattern (TIRP), which can learn models to predict whether and when an event of interest will occur, based on multiple instances of a pattern that end with the event., Results: The proposed methods achieved an average improvement of 5% AUROC over LSTM-FCN, the best-performed baseline model, out of the evaluated baseline models (RawXGB, Resnet, LSTM-FCN, and ROCKET) that were applied to real-life datasets., Conclusion: The proposed methods for predicting events continuously have the potential to be used in a wide range of real-world and real-time applications in diverse domains with heterogeneous multivariate temporal data. For example, it could be used to predict panic attacks early using wearable devices or to predict complications early in intensive care unit patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Incisional hernias (IH) are a significant postoperative complication with profound implications for patient morbidity and healthcare costs. The relationship between IH and perioperative factors in pancreatic surgery, with particular attention to preoperative biliary stents and pancreatic fistulas requires further exploration., Methods: This retrospective observational study examined adult patients who underwent open pancreatic surgeries via midline incision at a high-volume tertiary hepatopancreatobiliary center from January 2008 to December 2021. The study focused on IH incidence and associated risk factors, with particular attention to preoperative biliary stents and pancreatic fistulas., Results: In a cohort of 620 individuals undergoing pancreatic surgery, 351 had open surgery with at least one-year follow-up. Within a median follow-up of 794 days (IQR 1694-537), the overall incidence of IH was 17.38%. The highest frequency of IH was observed among patients who had a Pancreaticoduodenectomy (PD). Significant predictors for the development of IH within the entire study population in a multivariable analysis included perioperative biliary stenting (OR 2.05; 95% CI 1.06-3.96; p = 0.03), increased age at diagnosis (OR 2.05; 95% CI 1.06-3.96; p = 0.01), and BMI (OR 1.08; 95% CI 1.01-1.15; p = 0.01). In the subset of patients who underwent Pancreaticoduodenectomy (PD), although the presence of biliary stents was associated with a heightened occurrence of SSIs, it did not demonstrate a direct correlation with an increased incidence of incisional hernias (IH). The development of pancreatic fistulas did not show a significant correlation with IH in either the Distal Pancreatectomy with Splenectomy (DPS) or the PD patient groups., Conclusions: The study underscores a notable association between biliary stent placement and increased IH risk after PD, mediated by elevated SSI incidence. Pancreatic fistulas were not directly correlated with IH in the studied cohorts. Further research is necessary to validate these findings and guide clinical practice., (© 2024. The Author(s).)

Background: Between 2017 and 2021, the newly established Department of Neurosurgery at Shaare Zedek Medical Center in Jerusalem, a high volume metropolitan hospital, operated on 25 intradural lesions in 24 patients (one patient had multiple tumors). In this retrospective study, we review results and lessons learned as experienced surgeons opened a new service line., Methods: A multidisciplinary team was assembled and led by experienced neurosurgeons with skills in both microneurosurgery and complex spine care. Standard operative techniques were used. A chart review was done to assess complications and outcome., Results: 25 lesions were reviewed in 24 patients (14 female; 10 male) between the ages of 11-82 years of age. In 14 cases, gross total resection (GTR) was achieved; 11 cases underwent partial resection. Of the 11 non-GTR cases, 3 were initially planned as biopsies. In one case, there was a significant neurologic decline directly related to surgery. In a separate case, there was iatrogenic instability, necessitating further treatment., Conclusions: We identify six lessons learned in a nascent neurosurgical department, noting that surgical excellence is of paramount importance, but that the surgeon must also expand his/her role from master technician to team leader. Both microsurgical expertise for neural anatomy and understanding of spinal biomechanics for osseous anatomy is mandatory for surgery of SIDT. This retrospective analysis of our case series demonstrates experienced neurosurgeons can successfully deploy a new service line for challenging cases to the benefit of the hospital and local community., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The value of platelet characteristics as a prognostic factor in patients with pancreatic adenocarcinoma (PDAC) remains unclear., Methods: We assessed the prognostic ability of post-splenectomy thrombocytosis in patients who underwent left pancreatectomy for PDAC. Perioperative platelet count ratio (PPR), defined as the ratio between the maximum platelet count during the first five days following surgery and the preoperative level, was assessed in relation to long-term outcomes in patients who underwent left pancreatectomy for PDAC between November 2008 and October 2022., Results: A comparative cohort of 245 patients who underwent pancreaticoduodenectomy for PDAC was also evaluated. The median PPR among 106 patients who underwent left pancreatectomy was 1.4 (IQR1.1, 1.8). Forty-six had a PPR ≥ 1.5 (median 1.9, IQR1.7, 2.4) and 60 had a PPR < 1.5 (median 1.2, IQR1.0, 1.3). Patients with a PPR ≥ 1.5 had increased median overall survival (OS) compared to patients with a PPR < 1.5 (40 months vs. 20 months, p < 0.001). In multivariate analysis, PPR < 1.5 remained a strong predictor of worse OS (HR 2.24, p = 0.008). Among patients who underwent pancreaticoduodenectomy, the median PPR was 1.1 (IQR1.0, 1.3), which was significantly lower compared to patients who underwent left pancreatectomy ( p > 0.001) and did not predict OS., Conclusion: PPR is a biomarker for OS after left pancreatectomy for PDAC. Further studies are warranted to consolidate these findings.

Litter decomposition by microorganisms and animals is influenced by climate and has been found to be higher in warm and wet than in cold and dry biomes. We, however, hypothesized that the macrofaunal effect on decomposition should increase with temperature and aridity since larger animals are more tolerant to aridity than smaller organisms. This hypothesis was supported by our global analysis of macrofauna exclusion studies. Macrofauna increased litter mass loss on average by 40%, twofold higher than the highest previous estimation of macrofaunal effect on decomposition. The strongest effect was found in subtropical deserts where faunal decomposition had not been considered important. Our results highlight the need to consider animal size when exploring climate dependence of faunal decomposition, and the disproportionately large role of macrofauna in regulating litter decomposition in warm drylands. This new realization is critical for understanding element cycling in the face of global warming and aridification., (© 2023 The Authors. Ecology Letters published by John Wiley & Sons Ltd.)

Background: Major abdominal wall defects remain a highly morbid complication. Occasionally a fascial defect is encountered, that despite all surgical efforts, is unable to completely approximate at the midline. Here we describe our method and outcomes of using a bridging mesh when the posterior fascia was unable to be approximated during the repair of large postoperative ventral hernias using the modified Rives-Stoppa technique., Methods: A retrospective review was conducted looking at all the open abdominal wall hernia repairs between 2014 and 2020. The cohort of patients who had a bridge placed in addition to the traditional open modified Rives-Stoppa repair were used for this study., Results: Nineteen patients had a mesh inlay bridge placed in addition to a modified Rives-Stoppa repair with a sublay (retrorectus) Ultrapro mesh. For the inlay mesh 13 Symbotex composite meshes were placed and 6 Vicryl meshes used. The average surface area of the defect was 358.1 cm^2. The average length of hospitalization was 8.8 days with a range of 3-24 days. During the immediate postoperative course there were 6 minor complications. During the follow-up period there were 2 recurrences., Discussion: The use of inlay mesh bridge as an adjuvant to a modified Rives-Stoppa repair with a sublay ultrapro mesh is an effective technique for difficult abdominal wall repairs where the posterior fascia is unable to be approximated without tension., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The purpose of this study was to evaluate the quality of life (QoL), early post-operative complications, and hernia recurrence rate following laparoscopic enhanced-view Totally Extra-Peritoneal (eTEP) Rives-Stoppa (RS) for incisional and primary ventral hernia repair. Retrospective review of a prospectively maintained database of all patients undergoing eTEP-RS between 2017 and 2020. Data retrieved included demographics, and clinical and operative variables. QoL was assessed using the EuraHS-QoL scale prior to- and following eTEP-RS. During the study period, 61 patients met the inclusion criteria. Age and BMI were 62 (60.4 ± 13.8) years and 29.7 (30.4 ± 6) kg/m 2 , respectively. Incisional hernia was the most common pathology (n = 40, 65%) followed by primary ventral hernia (n = 21, 35%), with 24 patients (39%) having a previous hernia repair. Diastasis-recti repair was undertaken in 34 patients (55%), a concomitant inguinal hernia was repaired in 6 patients (10%), and 13 patients (21%) underwent transversus abdominis release (TAR). Median follow-up time was 13 months and 15 patients (25%) had at least 2 years of follow-up. Hernia recurrence was found in 4 patients (6.5%). Pre-operative and post-operative EuraHS-QOL questionnaire scores were available for 46 patients (75%) and showed significant improvement in pain (7 vs. 0.5, p < 0.0001; 5 vs. 0.5, p < 0.0001; 5 vs. 1.5; p < 0.006), restrictions (median of 5 vs. 0.5, p < 0.0001; 5 vs. 0, p < 0.0001; median of 5 vs. 1, p < 0.0001, of 6.5 vs. 1.5, p < 0.0001), and cosmetic appearance (8 vs. 4, p < 0.0001). Abdominal wall repair using the eTEP-RS approach significantly improves subjective QoL variables with an acceptable post-operative complications and hernia recurrence rates in a short-term follow-up., (© 2023. Italian Society of Surgery (SIC).)

Purpose: To describe the characteristics, treatment and outcome, in particular weaning from mechanical ventilation (MV), of critically ill Patients with prior psychiatric conditions (PPC)., Methods: Single center, 6-year, retrospective study comparing critically ill PPC to randomly sex and age matched cohort without PPC (1:1 ratio). Main outcome measure- adjusted mortality rates. Secondary outcome measures- unadjusted mortality, rates of MV, extubation failure and amount/dose of pre-extubation sedatives/analgesics., Results: Included were 214 patients per group. PPC adjusted mortality rates were higher in the ICU (14.0% vs 4.7%; OR 3.058 [95%CI 1.380, 6.774]; p = 0.006) and in-hospital (26.6% vs 13.1%; OR 2.639 [95% CI 1.496, 4.655]; p = 0.001). PPC had higher MV rates (63.6% vs 51.4%; p = 0.011). These patients were more likely to have more than two weaning attempts (29.4% vs 10.9%; p < 0.001), more commonly treated with >2 sedative drugs in the 48-h pre-extubation (39.2% vs 23.3%; p = 0.026) and received more propofol in the 24-h pre-extubation. PPC were more likely to self-extubate (9.6% vs 0.9%; p = 0.004) and had lower likelihood of success in planned extubations (50.0% vs 76.4%; p < 0.001)., Conclusion: Critically ill PPC had higher mortality rates than their matched counterparts. They also had higher MV rates and were more difficult to wean., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Strict iron regulation is essential for normal brain function. The iron homeostasis, determined by the milieu of available iron compounds, is impaired in aging, neurodegenerative diseases and cancer. However, non-invasive assessment of different molecular iron environments implicating brain tissue's iron homeostasis remains a challenge. We present a magnetic resonance imaging (MRI) technology sensitive to the iron homeostasis of the living brain (the r 1 -r 2 * relaxivity). In vitro, our MRI approach reveals the distinct paramagnetic properties of ferritin, transferrin and ferrous iron ions. In the in vivo human brain, we validate our approach against ex vivo iron compounds quantification and gene expression. Our approach varies with the iron mobilization capacity across brain regions and in aging. It reveals brain tumors' iron homeostasis, and enhances the distinction between tumor tissue and non-pathological tissue without contrast agents. Therefore, our approach may allow for non-invasive research and diagnosis of iron homeostasis in living human brains., (© 2023. Springer Nature Limited.)

BACKGROUND Bariatric surgeries, such as one anastomosis gastric bypass (OAGB), has become a popular treatment option for managing obesity and associated comorbidities, including type-2 diabetes mellitus (T2DM). However, severe starvation ketoacidosis is a rare but potentially life-threatening complication that can occur postoperatively in patients with T2DM. Despite the increasing prevalence of these surgeries, the existing literature has limited information on severe starvation ketoacidosis as a postoperative complication. It is essential for healthcare professionals to be aware of this complication, its manifestations, and risk factors to ensure patient safety and improve outcomes. Therefore, this article aims to address the current gap in the literature and provide a comprehensive review of severe starvation ketoacidosis as a postoperative complication of bariatric surgeries, specifically OAGB, and its associated risk factors and manifestations. CASE REPORT A 38-year-old man with severe obesity and inadequately managed T2DM underwent OAGB surgery. On the second postoperative day, the patient experienced severe starvation ketoacidosis, exhibiting symptoms such as drowsiness, fatigue, weakness, and Kussmaul breathing. Blood gas analysis indicated significant metabolic acidosis. He was quickly transferred to the Intensive Care Unit (ICU) and given intravenous glucose and insulin therapy. Following this intervention, he showed rapid recovery and normalization of blood gases. He was discharged 6 days after surgery with normal clinical examination results and laboratory indices. CONCLUSIONS This case study emphasizes the significance of thorough preoperative glycemic control, comprehensive perioperative multidisciplinary management, and close postoperative monitoring for diabetic patients undergoing metabolic and bariatric surgeries. By implementing these strategies, healthcare professionals can reduce the risk of complications such as hypoglycemia or hyperglycemia/diabetic ketoacidosis (DKA) and enhance patient outcomes. The case also highlights the need for continuous education and training for healthcare providers to identify and manage such rare complications effectively.

Background: Cochlear implants (CI) are the treatment of choice for individuals with severe to profound sensorineural hearing loss. A small group of patients, with pathology central to the cochlea, cannot benefit from CI. Examples in children include absence of the cochlear-nerve or cochlear aplasia. In these cases, implantation of an auditory brainstem implant (ABI), directly stimulating the cochlear nucleus, bypassing the inner-ear and auditory-nerve, may be beneficial., Objectives: Describe a series of children with ABI's treated in Shaare-Zedek, including the first ABI implantation in Israel (2017)., Methods: Of 9 patients with ABI's treated in Shaare Zedek Medical Center ,7 were children implanted between ages 2-8.6 years. Five boys and two girls. Surgeries were conducted in collaboration between neurosurgeons, neurotologists and audiologists (five implanted in Shaare-Zedek and two in New-York University). Follow-up was between 2-6 years. Hearing evaluation was conducted, mainly, with audiograms, categories of auditory performance (CAP), speech perception testing when possible and estimation of device use per day., Results: Six of the seven children, who initially underwent unsuccessful CI, had deficient auditory-nerves. One child had cochlear-aplasia. In 3 children hearing loss was part of the CHARGE syndrome. CAP scores ranged from 0-7 (0,1,3,5,5,7). One child was able to achieve open-set speech perception., Conclusions: Although functional auditory outcomes for children with ABI are inferior to CI recipients and are highly variable, some children were able to obtain significant benefit. In these children, who are not candidates for CI, the ABI presents the only chance for auditory awareness and may be recommended., Discussion: John Thomas Roland is a consultant and recipient of research support from Cochlear Americas.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Surgical resection is the standard treatment for parasagittal meningioma (PSM), but complete resection may be challenging due to superior sagittal sinus (SSS) involvement. The SSS may be partially or completely obstructed, and collateral veins are commonly present. Thus, knowing the status of the SSS in PSM cases prior to treatment is essential to a successful outcome. MRI is utilized prior to surgery in order to determine SSS status and to check for presence of collateral veins. The objective of this study is to evaluate the reliability of MRI in predicting both SSS involvement and presence of collateral veins in subsequent comparison to actual intra-operative findings, and to report on complications and outcomes., Methods: 27 patients were retrospectively analyzed for this study. A blinded radiologist reviewed all pre-operative images, noting SSS status and collateral vein presence. Intraoperative findings were obtained from hospital records to similarly categorize SSS status and collateral vein presence., Results: Sensitivity of the MRI to SSS status was found to be 100% and specificity was 93%. However, sensitivity and specificity of MRI to collateral vein presence was only 40% and 78.6%, respectively. Complications were experienced by 22% of patients, the majority neurologic in nature., Conclusion: MRI accurately predicted SSS occlusion status, but was less consistent in identification of collateral veins. These findings suggest MRI should be used with caution prior to PSM resection surgery particularly with regards to the presence of collateral veins which may complicate resection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: Laparoscopic adjustable gastric banding (LAGB) is in continuous decline due to low effectiveness and high reoperation rates. This study aims to evaluate outcomes of converting LAGB to one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG) for insufficient weight loss or weight regain., Materials and Methods: Retrospective comparative study, based on prospective registry database of a tertiary center (2012-2019)., Results: In all, 276 LAGB patients were converted to OAGB (n = 125) and SG (n = 151). Body mass index (BMI) at revision was 41.3 ± 6.6 and 42.3 ± 9.6 kg/m2 (P = 0.34) in OAGB and SG patients, respectively. Time interval was longer in OAGB patients (p < 0.001). Major early complication rates were comparable (2.4% and 4%; p = 0.46). At 5-years, OAGB patients had lower BMI (31.9 vs. 34.5 kg/m2; p = 0.002), and a higher total weight loss (25.1% vs. 18.8%; p = 0.003), compared with SG patients. Resolution of type 2 diabetes was higher in OAGB patients (93.3% vs. 66.6%; p = 0.047), while resolution of hypertension was not significantly different (84.6% and 80.5%; p = 0.68). Revision due to delayed complications was required in five (4%) OAGB patients and nine (8.6%) SG patients (p = 0.14)., Conclusion: OAGB for revision after LAGB due to insufficient weight loss or weight regain is safe, and has better effectiveness in weight reduction and resolution of type 2 diabetes than SG., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Heated intraperitoneal chemotherapy (HIPEC) was shown to induce immunogenicity of peritoneal metastases from colorectal cancer (PM-CRC) by induction of immunogenic cell death. We aimed to explore whether the addition of a checkpoint inhibitor would augment the effect of HIPEC in an experimental murine model of PM-CRC., Methods: PM-CRC was established in C57BL mice by intraperitoneal inoculation of MC38 colon cancer cells. HIPEC was administered using the closed technique with mitomycin C (MMC). Clinical and immunological parameters were compared between animals treated with HIPEC alone and those treated with HIPEC + anti-programmed death receptor-1 (aPD-1)., Results: MMC-based HIPEC increased the overall survival of animals compared with sham-treated animals (22.8; 95% confidence interval [CI] 21.14-24.53 vs. 18.9 days; 95% CI 17.6-20.3, p < 0.001). The extent of peritoneal disease as measured by the modified peritoneal carcinomatosis index was also reduced by HIPEC. This clinical benefit was accompanied by increased infiltration of CD8 + , CD68 + , and CD20 + cells into tumor metastases in HIPEC-treated animals compared with sham-treated animals. We identified heat shock protein (HSP) 90 as a potential immunogenic cell death protein whose expression is increased under HIPEC conditions (fold change: 2.37 ± 1.5 vs. 1 without HIPEC, p < 0.05). Combined HIPEC + PD-1 treatment ameliorated survival compared with HIPEC alone and sham treatment (24.66; 95% CI 20.13-29.2 vs. 19; 95% CI 15.85-22.14 and 14.33 days; 95% CI 9.6-19.04, respectively; p = 0.008). This clinical effect was accompanied by increased CD8 + tumor infiltration., Conclusions: HIPEC induced the expression of immunogenic cell death signals that can support an anti-tumor immune response. This response can be further exploited by a checkpoint inhibitor., (© 2023. Society of Surgical Oncology.)

Prevention and treatment of complications are the backbone of medical care, particularly in critical care settings. Early detection and prompt intervention can potentially prevent complications from occurring and improve outcomes. In this study, we use four longitudinal vital signs variables of intensive care unit patients, focusing on predicting acute hypertensive episodes (AHEs). These episodes represent elevations in blood pressure and may result in clinical damage or indicate a change in a patient's clinical situation, such as an elevation in intracranial pressure or kidney failure. Prediction of AHEs may allow clinicians to anticipate changes in the patient's condition and respond early on to prevent these from occurring. Temporal abstraction was employed to transform the multivariate temporal data into a uniform representation of symbolic time intervals, from which frequent time-intervals-related patterns (TIRPs) are mined and used as features for AHE prediction. A novel TIRP metric for classification, called coverage, is introduced that measures the coverage of a TIRP's instances in a time window. For comparison, several baseline models were applied on the raw time series data, including logistic regression and sequential deep learning models, are used. Our results show that using frequent TIRPs as features outperforms the baseline models, and the use of the coverage, metric outperforms other TIRP metrics. Two approaches to predicting AHEs in real-life application conditions are evaluated: using a sliding window to continuously predict whether a patient would experience an AHE within a specific prediction time period ahead, our models produced an AUC-ROC of 82%, but with low AUPRC. Alternatively, predicting whether an AHE would generally occur during the entire admission resulted in an AUC-ROC of 74%., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)