Immunodeficiency-Centromeric instability-Facial dysmorphism (ICF) syndrome is an inborn error of immunity characterized by progressive immune dysfunction and multi-organ disease usually treated with antimicrobial prophylaxis and immunoglobulin substitution. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment, but data on outcome are scarce. We provide a detailed description of disease characteristics and HSCT outcome in an international cohort of ICF syndrome patients. Eighteen patients (including all four genotypes) were enrolled. Main HSCT indications were infections (83%), enteropathy/failure to thrive (56%), immune dysregulation (22%) and myelodysplasia/haematological malignancy (17%). Two patients underwent pre-emptive HSCT after early diagnosis. Patients were transplanted between 2003-2021, at median age 4.3 years (range 0.5-19), after myeloablative or reduced-intensity conditioning, from matched sibling or matched family donors, matched unrelated or mismatched donors in 39%, 50% and 12% of cases respectively. Overall survival was 83% (all deaths occurred within the first 5 months post-HSCT; mean follow-up 54 months (range 1-185)). Acute GvHD occurred in 35% of patients, severe (grade III) in two (12%), while none developed chronic GvHD. At latest follow-up (median 2.2 years (range 0.1-14)), complete donor chimerism was achieved in 15/17 surviving patients. All survivors demonstrated normalized T and B cell numbers. Immunoglobulin substitution independence was achieved in all but two patients. All survivors recovered from pre-transplant infections, enteropathy/failure to thrive and immune dysregulation. All three patients transplanted at young age (≤ 3 years), after early diagnosis, survived. The favourable clinical and immunological HSCT outcome in this cohort of patients supports the timely use of this curative treatment in ICF syndrome.

UNASSIGNED: Postoperative pain (POP) is one of the most common and most important types of pain.
UNASSIGNED: The aim of this study was to compare the effects of pre-emptive oxycodone, diclofenac, and gabapentin on postoperative pain (POP) among patients with tibia fracture surgery.
UNASSIGNED: This double-blind three-group randomised controlled trial was conducted in 2023. Participants were 111 candidates for tibia fracture surgery under general anaesthesia. They were randomly allocated to oxycodone, gabapentin, and diclofenac groups through block randomisation. Baseline arterial oxygen saturation, heart rate, and blood pressure were documented before surgery and POP and sedation status were measured during postoperative recovery and 2, 4, 6, 12, and 24 h after surgery. Postoperative opioid analgesic use was also documented. The data were analysed using the SPSS software (v. 20.0) at a significance level of less than 0.05.
UNASSIGNED: Groups did not significantly differ from each other respecting participants\' baseline age, gender, body mass index, arterial oxygen saturation, heart rate, blood pressure, and surgery duration (P > 0.05). Moreover, there were no significant differences among the groups respecting POP and sedation status at different measurement time points (P > 0.05), except for six hours after surgery at which the POP mean score in the gabapentin group was significantly less than the other two groups (P = 0.001). Among-group differences respecting postoperative use of opioid analgesics and medication side effects were also insignificant (P > 0.05).
UNASSIGNED: Pre-emptive oxycodone, diclofenac, and gabapentin significantly reduce POP among patients with tibia fracture surgery, though gabapentin may produce more significant analgesic effects. All these three medications can be used for pre-emptive analgesia. Of course, the best pre-emptive analgesic agent is determined based on the opinion of the treating physician.

Outcomes for patients with chronic intestinal failure have improved with organization of experts into multidisciplinary teams delivering care in intestinal rehabilitation programs. There have been improvements in understanding of intestinal failure complications as well as development of newer therapies that have amplified the improvements in survival. In spite of this encouraging trend, patients who fail PN are often referred too late for intestinal transplantation. The author proposes a more rational framework that might allow earlier identification of intestinal failure patients at risk for PN-failure, who could appropriately be considered earlier for intestinal transplantation with improvements in overall outcomes.

Aim: Pre-emptive testing of pharmacogenomic (PGx) variations has potential to improve medication safety and effectiveness; however, testing is not routine. Given the newfound payor coverage of multigene testing and the potential value of testing within aging patients, it is imperative to test local PGx testing capabilities, report results to patients and providers, and determine the value of testing. Materials & methods: We designed a randomized clinical pilot of a pre-emptive PGx testing process using the electronic health record compared with usual care among an aging primary care population. Results & conclusion: The impact of the program on prescribing patterns, healthcare utilization and costs of care will be evaluated. We hypothesize that implementation of a pre-emptive multigene PGx panel is feasible among elderly, polypharmacy, primary care patients, measured by the number of enrolled patients with PGx results entered in the medical record. Health system wide PGx implementation, including capacity needed to integrate these valuable results, is also described.

Adverse drug reactions (ADRs) account for a large proportion of hospitalizations among adults and are more common in multimorbid patients, worsening clinical outcomes and burdening healthcare resources. Over the past decade, pharmacogenomics has been developed as a practical tool for optimizing treatment outcomes by mitigating the risk of ADRs. Some single-gene reactive tests are already used in clinical practice, including the DPYD test for fluoropyrimidines, which demonstrates how integrating pharmacogenomic data into routine care can improve patient safety in a cost-effective manner. The evolution from reactive single-gene testing to comprehensive pre-emptive genotyping panels holds great potential for refining drug prescribing practices. Several implementation projects have been conducted to test the feasibility of applying different genetic panels in clinical practice. Recently, the results of a large prospective randomized trial in Europe (the PREPARE study by Ubiquitous Pharmacogenomics consortium) have provided the first evidence that prospective application of a pre-emptive pharmacogenomic test panel in clinical practice, in seven European healthcare systems, is feasible and yielded a 30% reduction in the risk of developing clinically relevant toxicities. Nevertheless, some important questions remain unanswered and will hopefully be addressed by future dedicated studies. These issues include the cost-effectiveness of applying a pre-emptive genotyping panel, the role of multiple co-medications, the transferability of currently tested pharmacogenetic guidelines among patients of non-European origin and the impact of rare pharmacogenetic variants that are not detected by currently used genotyping approaches.

BACKGROUND: Pre-emptive analgesia is expected to decrease post-operative pain. The degree of soft tissue release is directly related to preoperative deformity; we presume the severity of pain has a similar correlation in patients undergoing total knee arthroplasty (TKA). The main purpose of this research was to evaluate the effects of pre-emptive analgesia of different drugs in TKA with different degrees of preoperative genu varus.
METHODS: In this prospective observational study, 67 patients were enrolled with different degrees of genu varus deformity. They were subdivided into two groups: those with ≥15° and those with <15° varus deformities of the knee. Etoricoxib 60 mg and pregabalin 75 mg were administered orally in all the patients as pre-emptive analgesia two hours before surgery. Parameters such as the amount of soft tissue release, visual analog score (VAS), knee range of motion, complications, etc. were documented from the pre-operative period to 72 hours post-TKA.
RESULTS: With pre-emptive analgesia in post-TKA patients, the VAS score demonstrated a statistically significant difference at 24, 48, and 72 hours. The comparison of intraoperative flexion between <15° and ≥15° showed a statistically significant difference with pre-emptive analgesia in post-TKA patients.
CONCLUSIONS: The use of etoricoxib 60 mg and pregabalin 75 mg, two hours before surgery reduced the pain scores in patients undergoing TKA with different degrees of genu varus and correlated with intraoperative parameters associated with soft medial tissue release for genu varus.

The broadening of the clinical definition of autism over time-the so-called, autism spectrum-has run in parallel with the growth of a neurodiversity movement that has reframed the concept of autism entirely. Without a coherent and evidence-based framework through which both of these advances can be situated, the field is at risk of losing definition altogether. In his commentary, Green describes such a framework, which has appeal because of its grounding in basic and clinical evidence, and its ability to guide its users through its real-world application in health care. An endless spectrum creates barriers to autistic children having their human rights met, but a denial of neurodiversity principles has the same effect. Green\'s framework holds great promise in coherently framing this sentiment. The real test of the framework is in its implementation, and all communities should walk that path together.

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BACKGROUND: Pre-emptive resection for intraductal papillary mucinous neoplasm (IPMN) aims to reduce the risk before invasive transformation has taken place. Pancreatic resections are highly associated with major morbidity and mortality. Long-term overall survival (OS) after resection for invasive IPMN (inv-IPMN) in early stages is favorable. Comparison of long-term OS for resected non-invasive IPMN and early staged inv-IPMN is poorly delineated. This study aims to compare outcomes for resected non-invasive IPMN and T1-staged inv-IPMN.
METHODS: All patients ≥18 years of age resected for IPMN up to stage T1 at Karolinska University Hospital between 2008 and 2020 were included. Two-year OS were compared between groups by chi-squared test, and 5-year OS was estimated using Kaplan-Meier method. Covariates associated with death was assessed in multivariable Cox regression model.
RESULTS: We included 284 patients, 264 (93%) non-invasive IPMN and 20 (7%) T1-staged inv-IPMN. Dysplasia of low grade (LGD) and high grade, i.e., tumor in situ (Tis) were present in 190 (67%) and 75 (26%) patients respectively. The 2-year OS for the entire cohort was 96%, and there were no differences between non-invasive and inv-IPMN (96% vs 92%, p = 0.203), nor between IPMN with LGD and Tis-T1b-staged IPMN (96% vs 95%, p = 0.734).
CONCLUSIONS: Two thirds of the specimen from pre-emptive resections were of LGD and did not involve superior OS than in situ or early cancer. Due to high complication burden, efforts should be made to avoid resection when LGD is probable and rather identify more accurate predictors for surgery.

UNASSIGNED: Many pain syndromes such as chronic phantom limb pain (PLP) and stump pain (SP), involving nociceptive and neuropathic pain, develop after amputation. Recent literature suggests that the use of regional blocks reduces repeated stimulation of transected nerve roots and thus prevents central sensitisation. This randomised, double-blind study was conducted to evaluate the effect of pre-emptive ultrasound-guided single-shot lateral sciatic nerve block on the occurrence of chronic pain at six months after traumatic below-knee amputation.
UNASSIGNED: Thirty patients undergoing traumatic lower limb amputation under general anaesthesia were randomised into two groups: Group B received sciatic nerve block pre-emptively using ultrasound with 20 ml of 0.75% ropivacaine, whereas group C received 20 ml of normal saline. Follow-up of patients was done till six months post-amputation. The primary objective was to assess the occurrence of chronic pain at six months. Pain at 15 days and one month after surgery, post-operative morphine consumption and post-operative nausea and vomiting (PONV) were the secondary outcomes assessed.
UNASSIGNED: The occurrence of PLP at six months was comparable in the two groups, group B (46.7%) and C (66.7%). None of the patients developed SP at six months. Median intensities of phantom pain were 1.0 (range, 1-2.0) versus 1.0 (range, 1-2.0) (P = 0.36), and median intensities of SP 2 (range, 2-3.0) versus 3 (range, 2-3.0) (P = 0.39) at 1 month.
UNASSIGNED: Pre-emptive sciatic nerve block did not decrease the occurrence or severity of chronic pain after traumatic below-knee amputation.