Epidemiology of acute lymphoblastic leukaemia in Sardinia, Italy: Age, sex, and environmental correlates.

Using a database of 1974-2003 incident cases of haematological malignancies, we explored the time trend, geographic spread and socio-economic and environmental correlates of ALL incidence in Sardinia, Italy, by sex and age. The age- and sex-standardized (World population) ALL incidence rate was 2.0 per 100,000 (95% CI 1.8 - 2.1) and showed variable trend patterns by sex and age. In the total population, ALL incidence showed an annual per cent change of -1.4% (95% CI -0.59 - -3.34) over the study period, with a knot separating a downward slope in 1974-1996 from an increase in 1996-2003. ALL incidence replicated such pattern in women but not men, whose incidence did not substantially vary over the study period (APC = -2.57%, 95% CI -5.45 - 0.26). Among women, the spatial analysis suggested a clustering of ALL in the southwestern part of the region, whilst only a commune had a high posterior probability of a high ALL incidence among men. Three unrelated communes showed a high posterior probability of ALL at age ≤ 24; only the most populated urban centre showed excess cases at age ≥ 25 years. There was no correlation between the geographic spread of ALL at ages ≤ 24 and ≥ 25 years (p = 0.082). Urban residence was a risk factor for the younger age group. Residences near industrial settlements and in the most populated urban centre were risk factors for subjects aged ≥ 25 years. Our findings suggest age-related differences in ALL aetiology.

Robotic repair of moderate-sized midline ventral hernias reduced complications, readmissions, and length of hospitalization compared to open techniques.

PURPOSE: To compare outcomes of robotic and open repair for uncomplicated, moderate-sized, midline ventral hernias. METHODS: From 2017 to 2021, patient characteristics and 30 day outcomes for all ventral hernias at our center were prospectively collected. We studied hernias potentially suitable for robotic repair: elective, midline, 3-10 cm rectus separation, no prior mesh, and no need for concomitant procedure. Robotic or open repair was performed by surgeon or patient preference. The primary outcome was any complication using Clavien-Dindo scoring. Secondary outcomes were operative time, length-of-stay, and readmissions. Regression identified predictors of complications. RESULTS: Of 648 hernias repaired, 70 robotic and 52 open repairs met inclusion criteria. The groups had similar patient demographics, co-morbidities, and hernia size, except that there were more immunosuppressed patients in the open group (11 versus 5 patients, p = 0.031). Complications occurred after 7 (13%) open repairs versus 2 (3%) robotic repairs, p = 0.036. Surgical site infection occurred after four open repairs but no robotic repair, p = 0.004. Length-of-stay averaged almost 3 days longer after open repair (4.3 ± 2.7 days versus 1.5 ± 1.4 days, p = 0.031). Readmission occurred after 6 (12%) oppen repairs but only 1 (1%) robotic repair. A long-term survey (61% response rate after mean follow-up of 2.8 years) showed that the HerQLes QOL score was better after robotic repair (46 ± 15 versus 40 ± 17, = 0.049). In regression models, only open technique predicted complications. CONCLUSIONS: Robotic techniques were associated with fewer complications, shorter hospitalization, fewer infections, and fewer readmissions compared to open techniques. Open surgical technique was the only predictor of complications.

Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6 mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1 N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P < .01) and femoral neck BMD decreased (mean -3.3%, P < .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (ß-diversity) postoperatively had greater increases in P1NP level (ρ = 0.48, P = .02) and greater bone loss at the femoral neck (ρ = -0.43, P = .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ = 0.56, P < .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ = 0.43, P = .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ = -0.43, P = .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, is a highly effective treatment for obesity because it produces dramatic weight loss and improves obesity-related medical conditions. However, it also results in abnormalities in bone metabolism. It is important to understand how LSG affects the skeleton, so that bone loss after surgery might be prevented. We studied adult men and women before and 6 mo after LSG, and we explored the relationship between the altered gut bacteria and bone metabolism changes. We found that: Those with greater shifts in their gut bacterial composition had more bone loss.Butyrate, a metabolite produced by gut bacteria from fermentation of dietary fiber, was associated with less bone breakdown and higher IGF-1 level (a bone-building hormone). We conclude that changes in the gut bacteria may contribute to the negative skeletal impact of LSG and reduced butyrate production by the gut bacteria leading to lower IGF-1 levels is a possible mechanism.

American Society for Metabolic and Bariatric Surgery position statement on one-anastomosis gastric bypass.

The following position statement is issued by the American Society for Metabolic and Bariatric Surgery in response to inquiries made to the society by patients, physicians, society members, hospitals, health insurance payors, and others regarding one-anastomosis gastric bypass as a treatment for obesity and metabolic disease. This statement is based on current clinical knowledge, expert opinion, and published peer-reviewed scientific evidence available at this time. The statement may be revised in the future as more information becomes available.

ASMBS statement on metabolic and bariatric surgery for beneficiaries of Centers for Medicare and Medicaid Services with a review of the literature.

This position statement is issued by the American Society for Metabolic and Bariatric. Surgery in response to inquiries made to the Society by patients, physicians, Society members, hospitals, health insurance payors, the media, and others regarding the access and outcomes of metabolic and bariatric surgery for beneficiaries of Centers for Medicare and Medicaid Services. This position statement is based on current clinical knowledge, expert opinion, and published peer-reviewed scientific evidence available at this time. The statement is not intended to be and should not be construed as stating or establishing a local, regional, or national standard of care. This statement will be revised in the future as additional evidence becomes available.

Incidence and Bayesian Mapping of Myeloid Hematologic Malignancies in Sardinia, Italy.

BACKGROUND: The epidemiology of myeloid hematologic malignancies in Italy has been poorly investigated. METHODS: We used a validated database of 1974-2003 incident cases of hematologic malignancies among the resident population (all ages) of Sardinia, Italy, to describe the incidence of myeloid malignancies overall (N = 4389 cases) and by subtype. We investigated the time trend of acute myeloid leukemia (N = 1227 cases), chronic myeloid leukemia (N = 613 cases), and myelodysplastic syndrome (N = 1296 cases), and used Bayesian methods to explore their geographic spread, and Poisson regression analysis to estimate their association with environmental and socio-economic factors. RESULTS: The annual standardized (world population) incidence rate (IR) of myeloid malignancies over the study period was 6.5 per 100,000 (95% CI 6.2-6.7). Myelodysplastic syndromes were the most prevalent subgroup (IR = 1.7, 95% CI 1.5-1.8). Incidence of all myeloid malignancies combined increased sharply during the study period with an annual percent change (APC) of 10.06% (95% CI 9.51-10.61), 19.77% for myelodysplastic syndromes (95% CI 19.63-19.91), and 3.18% (95% CI 2.99-3.37) for acute myeloid leukemia. Chronic myeloid leukemia did not show an upward trend. Apart from sporadic excesses in small rural communities and the major urban area, there was no evidence of spatial clustering. The risk of myeloid malignancies increased with increasing prevalence of sheep breeding. CONCLUSIONS: Our results might prompt further research on the local genetic and environmental determinants of myeloid hematologic malignancies.

Results of the European Society of Toxicologic Pathology Survey on the Use of Artificial Intelligence in Toxicologic Pathology.

The European Society of Toxicologic Pathology (ESTP) initiated a survey through its Pathology 2.0 workstream in partnership with sister professional societies in Europe and North America to generate a snapshot of artificial intelligence (AI) usage in the field of toxicologic pathology. In addition to demographic information, some general questions explored AI relative to (1) the current status of adoption across organizations; (2) technical and methodological aspects; (3) perceived business value and finally; and (4) roadblocks and perspectives. AI has become increasingly established in toxicologic pathology with most pathologists being supportive of its development despite some areas of uncertainty. A salient feature consisted of the variability of AI awareness and adoption among the responders, as the spectrum extended from pathologists having developed familiarity and technical skills in AI, to colleagues who had no interest in AI as a tool in toxicologic pathology. Despite a general enthusiasm for these techniques, the overall understanding and trust in AI algorithms as well as their added value in toxicologic pathology were generally low, suggesting room for the need for increased awareness and education. This survey will serve as a basis to evaluate the evolution of AI penetration and acceptance in this domain.

Epidemiology of Chronic Lymphocytic Leukemia in Sardinia, Italy (1974-2003).

Several reports have described a worldwide increasing incidence of chronic lymphocytic leukemia (CLL) dating back seven to eight decades. Although genetic susceptibility would be an implausible explanation, the determinants of this upward trend and its spatial coordinates are poorly understood. We explored CLL incidence in Sardinia, Italy, using a validated database including the 1700 CLL cases diagnosed during 1974-2003. We applied Bayesian methods to map the CLL probability by administrative unit and Poisson regression analysis to investigate socioeconomic and environmental determinants adjusting by possible confounders. The standardized (Standard European population) incidence rate for the Sardinian population over the study period was 5.1 per 100,000 (95% confidence interval [CI] 4.9-5.3), increased annually by 5.8% (95% CI 5.7-6.0) consistently by sex and age, and was more noticeable in urban areas. Five administrative units exceeded the 95% posterior probability of an elevated CLL incidence: these were rural areas spread over the regional territory, not suggestive of spatial clustering. The Poisson regression analysis showed that the risk was elevated in urban areas (RR = 1.11, 95% CI 1.05-1.17), among residents ≥ 30 km from the nearest hospital (RR = 1.09, 95% CI 1.06-1.12), and with the local prevalence of cork harvesting (RR = 1.62, 95% CI 1.12-2.34). Our results suggest that better access to health care facilities and improvements in diagnostic efficacy might have generated the observed upward trend in CLL incidence, along with contributing environmental factors.

American Society for Metabolic and Bariatric Surgery literature review on the effect of Roux-en-Y gastric bypass limb lengths on outcomes.

This literature review is issued by the American Society for Metabolic and Bariatric Surgery regarding limb lengths in Roux-en-Y gastric bypass (RYGB) and their effect on metabolic and bariatric outcomes. Limbs in RYGB consist of the alimentary and biliopancreatic limbs and the common channel. Variation of limb lengths in primary RYGB and as a revisional option for weight recurrence after RYGB are described in this review.

First uterine transplant case at the Royal Prince Alfred Hospital.

Uterine transplantation (UT) is an emerging medical treatment for women affected by absolute uterine factor infertility (AUFI). To date there have been over 90 documented cases of UT performed worldwide, with over 50 live births. UT allows women affected by AUFI the opportunity to carry and deliver a childd. The Royal Prince Alfred Hospital (RPAH) introduced a UT study in 2019; however, due to the impacts of the COVID pandemic the study was placed on hold for two years. In February 2023, RPAH performed the centre's first UT from a living unrelated donor to a 25-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome. The donor and recipient surgeries were uncomplicated and both are recovering well in the early post-operative period.

Cerebral enhancement in MOG antibody-associated disease.

INTRODUCTION: Limited data exist on brain MRI enhancement in myelin-oligodendrocyte-glycoprotein (MOG) antibody-associated disease (MOGAD) and differences from aquaporin-4-IgG-positive-neuromyelitis-optica-spectrum-disorder (AQP4+NMOSD), and multiple sclerosis (MS). METHODS: In this retrospective observational study, we identified 122 Mayo Clinic MOGAD patients (1 January 1996-1 July 2020) with cerebral attacks. We explored enhancement patterns using a discovery set (n=41). We assessed enhancement frequency and Expanded Disability Status Scale scores at nadir and follow-up in the remainder (n=81). Two raters assessed T1-weighted-postgadolinium MRIs (1.5T/3T) for enhancement patterns in MOGAD, AQP4+NMOSD (n=14) and MS (n=26). Inter-rater agreement was assessed. Leptomeningeal enhancement clinical correlates were analysed. RESULTS: Enhancement occurred in 59/81 (73%) MOGAD cerebral attacks but did not influence outcome. Enhancement was often patchy/heterogeneous in MOGAD (33/59 (56%)), AQP4+NMOSD (9/14 (64%); p=0.57) and MS (16/26 (62%); p=0.63). Leptomeningeal enhancement favoured MOGAD (27/59 (46%)) over AQP4+NMOSD (1/14 (7%); p=0.01) and MS (1/26 (4%); p<0.001) with headache, fever and seizures frequent clinical correlates. Ring enhancement favoured MS (8/26 (31%); p=0.006) over MOGAD (4/59 (7%)). Linear ependymal enhancement was unique to AQP4+NMOSD (2/14 (14%)) and persistent enhancement (>3 months) was rare (0%-8%) across all groups. Inter-rater agreement for enhancement patterns was moderate. CONCLUSIONS: Enhancement is common with MOGAD cerebral attacks and often has a non-specific patchy appearance and rarely persists beyond 3 months. Leptomeningeal enhancement favours MOGAD over AQP4+NMOSD and MS.

Retinal Vasculopathy With Cerebral Leukoencephalopathy and Systemic Manifestations: Critical Role of Retina Specialists.

Purpose: To describe a case of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) to enhance early recognition of this often-missed diagnosis. Methods: A case report is presented. Results: A 50-year-old woman with a history of Raynaud phenomenon, memory difficulties, and a family history of strokes was referred for evaluation of a bilateral, small-vessel, occlusive disease refractory to immunosuppressive therapy. An extensive workup for treatable causes was unrevealing. Fifteen months after presentation, brain imaging showed white-matter lesions and dystrophic calcification, which led to the discovery of a pathogenic variant in TREX1 and the diagnosis of RVCL-S. Conclusions: Retina specialists play a critical role in the timely diagnosis of RVCL-S. Although the findings in this condition can mimic those in other common retinal vascular disorders, there are key characteristics that increase the suspicion for RVCL-S. Early recognition might decrease unnecessary therapies and procedures.

Pregnancy Conceptualizations in Women Who Have Had Recent Bariatric Surgery.

Objectives: To describe bariatric surgery patients' perioperative conceptualizations about pregnancy. Materials and Methods: We performed a secondary analysis of a cross-sectional study performed in 2016, evaluating a nationally recruited convenience sample of U.S. women aged 18-45 years who underwent bariatric surgery within the past 24 months. We assessed four pregnancy constructs: intent, desire, emotional orientation, and importance to avoid. We examined relationships between constructs, with time since surgery, postoperative pregnancy, and contraceptive use using descriptive statistics. Results: We included 363 eligible women (response rate 80%). Participant median age was 36 years, 71% (n = 258) were White, 77% (n = 279) were sexually active at the time of the study, and 39% (n = 140) experienced preoperative infertility. Most reported no desire to become pregnant (59%, n = 175) and that it was important to avoid pregnancy (78%, n = 283) within the first 24 months after surgery. Relationships between constructs were complex. Respondents in their first postoperative year more likely reported they would feel upset about a hypothetical pregnancy (40%, n = 74) than those in their second year (27%, n = 48, p = 0.02). Of those with a postoperative pregnancy, 46% (n = 17) felt it was important to avoid pregnancy compared with 81% (n = 266) of those who did not have a pregnancy (p < 0.001). Most used postoperative contraception (66%, n = 241), and those who felt it was important to avoid pregnancy more likely used contraception (82%, n = 197) than those who did not feel it was important (18%, n = 44, p = 0.01). Conclusions: Women undergoing bariatric surgery have diverse and complex conceptualizations about future pregnancy. These varied based on time from surgery and influenced postoperative contraceptive use.

Intestinal Calcium Absorption Decreases After Laparoscopic Sleeve Gastrectomy Despite Optimization of Vitamin D Status.

CONTEXT: Laparoscopic sleeve gastrectomy (LSG), now the most commonly performed bariatric operation, is a highly effective treatment for obesity. While Roux-en-Y gastric bypass is known to impair intestinal fractional calcium absorption (FCA) and negatively affect bone metabolism, LSG's effects on calcium homeostasis and bone health have not been well characterized. OBJECTIVE: We determined the effect of LSG on FCA, while maintaining robust 25-hydroxyvitamin D (25OHD) levels and recommended calcium intake. DESIGN, SETTING, PARTICIPANTS: Prospective pre-post observational cohort study of 35 women and men with severe obesity undergoing LSG. MAIN OUTCOMES: FCA was measured preoperatively and 6 months postoperatively with a gold-standard dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and bone mineral density (BMD) by dual-energy X-ray absorptiometry and quantitative computed tomography. RESULTS: Mean ± SD FCA decreased from 31.4 ± 15.4% preoperatively to 16.1 ± 12.3% postoperatively (P < 0.01), while median (interquartile range) 25OHD levels were 39 (32-46) ng/mL and 36 (30-46) ng/mL, respectively. Concurrently, median 1,25-dihydroxyvitamin D level increased from 60 (50-82) pg/mL to 86 (72-107) pg/mL (P < 0.01), without significant changes in parathyroid hormone or 24-hour urinary calcium levels. Bone turnover marker levels increased substantially, and areal BMD decreased at the proximal femur. Those with lower postoperative FCA had greater areal BMD loss at the total hip (ρ = 0.45, P < 0.01). CONCLUSIONS: FCA decreases after LSG, with a concurrent rise in bone turnover marker levels and decline in BMD, despite robust 25OHD levels and with recommended calcium intake. Decline in FCA could contribute to negative skeletal effects following LSG.

IT/QA and Regulatory Aspects of Digital Pathology: Results of the 8th ESTP International Workshop.

Digital toxicologic histopathology has been broadly adopted in preclinical compound development for informal consultation and peer review. There is now increased interest in implementing the technology for good laboratory practice-regulated study evaluations. However, the implementation is not straightforward because systems and work processes require qualification and validation, with consideration also given to security. As a result of the high-throughput, high-volume nature of safety evaluations, computer performance, ergonomics, efficiency, and integration with laboratory information management systems are further key considerations. The European Society of Toxicologic Pathology organized an international expert workshop with participation by toxicologic pathologists, quality assurance/regulatory experts, and information technology experts to discuss qualification and validation of digital histopathology systems in a good laboratory practice environment, and to share the resulting conclusions broadly in the toxicologic pathology community.

Identifying risk factors for post-operative bleeding in women undergoing loop electrosurgical excision procedure for cervical dysplasia.

BACKGROUND: Loop electrosurgical excision is a procedure utilised in the treatment of high-grade squamous intraepithelial lesion (HSIL) of the cervix. Post-operatively women may experience immediate and/or delayed per vaginal bleeding. AIMS: The objective of this prospective pilot study was to assess the feasibility of identifying and quantifying patients' subjective experiences of post-operative bleeding following a loop electrosurgical excision procedure (LEEP) for HSIL. In addition, an analysis of demographical, lifestyle and surgical factors was undertaken to assess for any statistically significant correlation with post-operative bleeding. MATERIALS AND METHODS: This study included 110 patients who underwent a LEEP for biopsy-proven or suspected HSIL between 2017 and 2020. Subjective data were collected from weekly post-operative surveys and correlated with procedural data. Primary outcome assessed was the subjective rate of bleeding experienced. Baseline demographics were age, body mass index (BMI), specimen size, human papilloma virus variant and histopathology. Other variables of interest collected were exercise intensity, and alcohol intake. RESULTS: No association of statistical significance was discovered between age, BMI, or day of menstrual cycle. There was a statistically significant association between exercise intensity or specimen size (greater than the median) and increased bleeding, primarily in the first 2 weeks. CONCLUSIONS: Women who undergo intense or prolonged exercise in the post-operative period may experience heavier bleeding particularly in the first 2 weeks post-LEEP. Heavy bleeding was also associated with a larger specimen size. There was no correlation between BMI, age or any other demographical factor.