患儿 男，1月11日龄，因发现皮肤黄染1个月余就诊，肝功能示转氨酶升高、胆汁淤积。因患儿经治疗后粪便色浅，肝功能无改善，肝脏穿刺病理示细胆管增生，遂行胆道探查术，但胆道通畅。术后继续给予护肝利胆治疗。患儿3月龄时发现其在黄疸消退后仍存在显著增高的胆汁酸水平，最终行基因检测确诊钠牛磺胆酸共转运多肽缺陷病。.

BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) results from a pathogenic variant in the hemizygous subunit of the SLC16A2 gene, which encodes monocarboxylate transporter 8 and follows an X-linked recessive pattern. AHDS manifests as neuropsychomotor developmental delay, intellectual disability, movement disorders, and thyroid hormone abnormalities. It is frequently misdiagnosed as cerebral palsy or hypothyroidism.
METHODS: A 9-month-old male infant exhibited poor head control, hypodynamia, motor retardation, hypertonic limbs, and thyroid abnormalities. Despite levothyroxine supplementation and rehabilitation therapy, no improvements were observed. Whole-exome sequencing identified a novel nonsense mutation in SLC16A2 (c.124G > T, p.E42X), which unequivocally established the diagnosis.
METHODS: AHDS was confirmed.
METHODS: Levothyroxine treatment commenced early in infancy, followed by 3 months of rehabilitation therapy, starting at 5 months of age. The combined administration of levothyroxine and methimazole was initiated at 1 year and 10 months of age, respectively.
RESULTS: While improvements were noted in thyroid hormone levels, neurological developmental delays persisted.
CONCLUSIONS: AHDS should be considered in patients presenting with atypical neurological features and thyroid hormone abnormalities such as elevated triiodothyronine and decreased thyroxine levels. The early utilization of exome sequencing aids in prompt diagnosis. The identified SLC16A2 nonsense mutation correlates with severe neurological phenotypes and adds to the spectrum of genetic variations associated with AHDS.

BACKGROUND: Deficiencies in the thyroid hormone transporter monocarboxylate 8 (MCT8) due to pathogenic variants in the SLC16A2 gene (OMIM 300095) result in a complex phenotype with main endocrine and neurologic symptoms. This rare disorder, named Allan-Herndon-Dudley syndrome (AHDS) (OMIM 300523), is inherited in an X-linked trait. One of the prominent features of AHDS is the presence of movement disorders (MD), which are complex and carry a significant burden of the disease.
METHODS: Patient 1: male with hypotonia since birth, developmental delay, dystonic posturing at 4 months and at 15 months, and startle reaction developed with sensory stimuli. Patient 2: male, at 2 months, shows hypotonia and developmental delay, paroxysmal episodes triggered by a stimulus with sudden blush, tonic asymmetric posture, and no epileptiform activity. At 10 months, generalized dystonic posturing. Patient 3: typical neurodevelopmental milestones until 6 months; at 24 months, dystonia, startle reaction, and upper motoneuron signs.
CONCLUSIONS: We aim to describe our patients diagnosed with AHDS, focusing on MD phenomenology and strengthening the phenotype-genotype correlations for this rare condition.

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Background: Large cardiovascular outcomes trials in individuals with heart failure, with and without diabetes, have demonstrated a significant risk reduction in the composite outcome of cardiovascular death or hospitalizations for heart failure with SGLT2 inhibitor therapy. These positive outcomes have led to the recommendation that SGLT2 inhibitors serve as backbone therapy in patients with heart failure reduced ejection fraction (HFrEF). To date, there has not been enough participants in clinical trials on concomitant SGLT2 inhibitor and angiotensin receptor-neprilysin inhibitor therapy to evaluate the benefits and risks of combination therapy with these two agents outside of smaller subgroup analyses. Case Summary: This case describes a Black female with diabetes meeting her glycemic targets and concomitant stable NYHA FC II HFrEF on guideline-directed medical therapy (GDMT) with sacubitril/valsartan, spironolactone and metoprolol succinate who developed severe hypotension and dehydration requiring hospitalization after initiation of SGLT2 inhibitor therapy. Practice Implications: This case report raises the question of whether those with type 2 diabetes, and/or those on background angiotensin receptor-neprilysin inhibitor therapy, who are euvolemic or sensitive to diuretic therapy should be started on lower dose dapagliflozin and titrated to 10 mg daily based on response. It also raises awareness to the potential increased diuretic effect produced with concomitant use of sacubitril/valsartan and dapagliflozin. Caution and education to mitigate the risk for volume depletion should be provided to those patients who are euvolemic and initiated on a SGLT2 inhibitor, regardless of their background diuretic and GDMT. Conclusion: Future research should focus on the benefits and safety considerations and provide education on how to best initiate and adjust SGLT2 inhibitors in the setting of sacubitril/valsartan use in diverse heart failure patient populations.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are glucose-lowering agents being increasingly used for cardio-renal protection in patients with or without type 2 diabetes (T2DM). This systematic review identified the clinical risk factors and outcomes of diabetic ketoacidosis (DKA) in patients undergoing bariatric and metabolic surgery (BMS) on SGLT2i. We found 12 studies with a total of 16 patients (10 females; mean age of 51 years). Apart from one patient, all patients developed DKA in the post-operative period presenting at a median of 5 days after surgery. Most of the patients were euglycaemic on presentation with DKA. Patients undergoing BMS on SGLT2i are at increased risk of developing DKA that can mimic post-operative surgical complications causing diagnostic dilemmas, especially with the euglycaemic variant, and delaying treatment.

BACKGROUND: I-131 radioiodine false-positive findings in postoperative patients with differentiated thyroid cancer (DTC) should be recognized to avoid unnecessary therapies.
METHODS: A 50-year-old man underwent I-131 therapy 3 times, including the initial ablative therapy after total thyroidectomy for papillary thyroid cancer. The initial I-131 posttherapeutic whole-body scintigraphy showed 2 cervical and one superior mediastinal focal I-131 positive uptake lesions. The serum thyroglobulin level was negative every time when the radioiodine therapy was performed. Although the 2 cervical positive uptake lesions disappeared after the second therapy, the superior mediastinal I-131 positive uptake persisted even after the third therapy, and this lesion was suspicion of I-131 therapy-resistant node metastasis.
RESULTS: The lesion was resected, and the pathological diagnosis with immune-histochemical analysis was a thymic cyst with thymic epithelial cells having a weak expression of the sodium-iodide symporter (NIS).
CONCLUSIONS: The false-positive result may be attributed to the NIS expression in the thymic cyst epithelial cells. It is necessary to include a thymic cyst in the differential diagnosis, when I-131 uptake is noted in the superior mediastinal region on I-131 posttherapeutic scans of patients with postoperative DTC. Although the I-131 positive uptake in a thymic cyst may be influenced by the I-131 administered dose and scan timing after I-131 administration, the NIS expression may be essential to the false-positive uptake in a thymic cyst.

Sodium glucose co-transporter 2 inhibitors (SGLT2is) are used to prevent cardiovascular complications in type 2 diabetes mellitus (T2DM) and newly indicated to treat heart failure (HF). Loop diuretics are commonly prescribed to manage volume overload in HF and may increase the risk of volume depletion in real-world practice. This study evaluated the risk of volume depletion following concomitant use of SGLT2is and loop diuretics in veterans.
Veterans with T2DM were included if they received concomitant loop diuretics and SGLT2is and experienced at least one volume depletion event between December 2012 and December 2019, utilizing a self-controlled case series design. Concomitant prescribing periods were divided into focal windows of 1 to 14 days, 14 to 28 days, and greater than 28 days. Incidence rate ratios (IRR) were estimated using multivariable Poisson regressions adjusted for age and renal function.
3352 patients experienced at least one volume depletion event and were concomitantly prescribed SGLT2is and loop diuretics at least once. The risk of volume depletion increased in the treatment versus control windows during the 1 to 14-day window (IRR = 1.82, 95% CI 1.63-2.02) the 15-to-28-day window (IRR = 1.46, 95% CI 1.28-1.67), and the greater than 28-day window (IRR = 1.22, 95% CI 1.21-1.34).
Concomitant prescribing of SGLT2is and loop diuretics is associated with an increased risk of volume depletion, an effect that attenuates with longer therapy durations. Prescribers need to closely monitor fluid status in patients receiving concomitant therapy, especially those with advancing age or with eGFR below 60.

Schizophrenia (SCZ) is a debilitating, destructive, and chronic mental disorder and affects approximately one percent of the human population. Diagnosis in psychiatry is based on the patient\'s descriptions of his/her symptoms, interviewer\'s observations, history of disorder over time, and response to treatment. All of these data measure phenotype-based functions. But it appears that accurate diagnosis of such a complex disorder must be based on valid and reliable factors. In the present study, gene selection was based on the possible role of γ-aminobutyric acid (GABA) in psychopathology of SCZ and expression in blood. We evaluated the association of Na+-K+-Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) genes\' messenger ribonucleic acid (mRNA) levels, and also the NKCC1/KCC2 ratio with positive and negative syndrome scale (PANSS) and brief psychiatric rating scale (BPRS) scores in an SCZ group. By using real-time PCR (RT-PCR), the present study is the first attempt to explore levels of NKCC1 and KCC2 expression at mRNA level and their relative expression in human peripheral blood of patients with SCZ. Our results showed that the NKCC1 to KCC2 mRNA ratio is significantly increased (but based on the delta cycle of threshold [∆Ct] is significantly lower) in the total sample of cases rather than controls (p = 0.045) and also higher in male sample cases rather than male controls (p = 0.016). In female samples, we found a trend toward a significant effect between the case and control participants (p = 0.075). We also found statistically significant association between mRNA of NKCC1 and KCC2 genes and NKCC1/KCC2 mRNA ratio with the positive and negative syndrome scale (PANSS) and brief psychiatric rating scale (BPRS) scores.