Radioactive Iodine Therapy in Differentiated Thyroid Cancer: An Update on Dose Recommendations and Risk of Secondary Primary Malignancies.

Radioactive iodine (RAI) therapy with iodine-131 is performed in select cases of differentiated thyroid cancer (DTC), typically for remnant ablation, adjuvant therapy, or treatment of known persistent disease. Herein, we review updated RAI dose recommendations and associated risks of secondary primary malignancy (SPM). RAI dose is usually chosen empirically based on the risk assessment of tumor recurrence and other factors. Dose recommendations differ slightly among relevant medical societies. As of April 2024, most medical societies, including the American Thyroid Association (ATA), European Thyroid Association (ETA), Society of Nuclear Medicine and Molecular Imaging/European Association of Nuclear Medicine (SNMMI/ EANM), and National Comprehensive Cancer Network (NCCN), recommend a dose of 1.11 GBq (30 mCi) I-131 for remnant ablation. For adjuvant therapy, the recommended RAI dose ranges from 1.11 to 3.7 GBq (30-100) mCi I-131, although doses up to 5.6 GBq (150 mCi) may also be considered. In patients with known or suspected metastatic disease, at least 3.7 GBq (100 mCi) I-131 should be administered, and RAI doses as high as 7.4 GBq (200 mCi) may be justified depending on the suspected tumor burden and extent. Dosimetry has the advantage of tailoring the RAI dose to each patient's pharmacokinetics, resulting in ≥ 7.4 GBq (200 mCi) of I-131 in most cases. There is an ongoing debate about the risk of developing SPM due to RAI therapy, with several multicenter studies and meta-analyses concerning SPM being published in the last 2 years. The incidence of RAI-associated SPM varies according to the study design and detection method. Several studies showed no increased incidence, and there was no specific secondary cancer or cancer group linked to RAI exposures. Some reports indicated that cumulative RAI doses exceeding 5.6-7.4 GBq (150-200 mCi) were found to represent an increased risk for developing SPM. However, a clearly defined dose threshold cannot be provided based on the current literature. Nonetheless, caution should be exercised when considering repeated RAI therapies for persistent metastatic PTC, with a cumulative dose exceeding 37.0 GBq (1,000 mCi), due to the potential risk of developing SPM and other long-term toxicity. Further research is warranted to understand better the relationship between RAI dose and the risk of SPM.

The infected diabetic foot: Analysis of diabetic and non-diabetic foot infections.

The aim of this study was to compare outcomes of moderate and severe foot infections in people with and without diabetes mellitus (DM). We retrospectively evaluated 382 patients (77% with DM and 23% non-DM). We collected demographic data, co-morbidities and one-year outcomes including healing, surgical interventions, number of surgeries, length of stay, re-infection and re-hospitalisation. DM patients required more surgeries (2.3 ± 2.2 vs. 1.7 ± 1.3, p = 0.01), but did not have a longer hospital length of stay during the index hospitalisation (DM 10.9 days ±9.2 vs. non-DM = 8.8 days ±5.8, p = 0.43). After the index hospitalisation, DM patients had increased rates of re-hospitalisation for any reason (63.3% vs. 35.2%, CI 1.9-5.2, OR 3.2, p < 0.01), re-infection at the index wound infection site (48% vs. 30.7%, CI 1.3-3.5, OR 2.1, p < 0.01), re-hospitalisation for a foot pathology (47.3% vs. 29.5%, CI 1.3-3.6, OR 2.1, p < 0.01), and longer times to ulcer healing (151.8 days ±108.8 vs. 108.8 ± 90.6 days, p = 0.04). Patients with DM admitted to hospital with foot infections have worse clinical outcomes during the index hospitalisation and are more likely to have re-infection and re-admission to hospital in the next year.

The infected diabetic foot: Modulation of traditional biomarkers for osteomyelitis diagnosis in the setting of diabetic foot infection and renal impairment.

The objective of this paper was to investigate erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in diagnosing pedal osteomyelitis (OM) in patients with and without diabetes, and with and without severe renal impairment (SRI). This was a retrospective cohort study of patients with moderate and severe foot infections. We evaluated three groups: Subjects without diabetes (NDM), subjects with diabetes and without severe renal insufficiency (DM-NSRI), and patients with diabetes and SRI (DM-SRI). SRI was defined as eGFR <30. We evaluated area under the curve (AUC), cutoff point, sensitivity and specificity to characterize the accuracy of ESR and CRP to diagnose OM. A total of 408 patients were included in the analysis. ROC analysis in the NDM group revealed the AUC for ESR was 0.62, with a cutoff value of 46 mm/h (sensitivity, 49.0%; specificity, 76.0%). DM-NSRI subjects showed the AUC for ESR was 0.70 with the cutoff value of 61 mm/h (sensitivity, 68.9%; specificity 61.8%). In DM-SRI, the AUC for ESR was 0.67, with a cutoff value of 119 mm/h (sensitivity, 46.4%; specificity, 82.40%). In the NDM group, the AUC for CRP was 0.55, with a cutoff value of 6.4 mg/dL (sensitivity, 31.3%; specificity, 84.0%). For DM-NSRI, the AUC for CRP was 0.70, with a cutoff value of 8 mg/dL (sensitivity, 49.2%; specificity, 80.6%). In DM-SRI, the AUC for CRP was 0.62, with a cutoff value of 7 mg/dL (sensitivity, 57.1%; specificity, 67.7%). While CRP demonstrated relatively consistent utility, ESR's diagnostic cutoff points diverged significantly. These results highlight the necessity of considering patient-specific factors when interpreting ESR results in the context of OM diagnosis.

MRSA infection, re-infection and clinical outcomes in diabetic foot infections.

The aim was to investigate methicillin-resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient-level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re-infections. We identified MRSA conversion (MSSA to MRSA) in re-infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re-infections in patients who initially had MSSA in their cultures. Patients with re-infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1-year follow-up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re-infection, amputation, re-ulceration, re-admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re-infections. The RR of having MRSA was 2.2 times higher in re-infections. Patients with MRSA used more antibiotics during the 1-year follow-up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens.

Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients.

Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) of both hematopoietic and nonhematopoietic origin. While the significance of gonad-derived estradiol to bone health has been investigated, there is limited understanding regarding the relative contribution of BMC derived estrogens to bone metabolism. To elucidate the role of BMC derived estrogens in male bone, irradiated wild-type C57BL/6J mice received bone marrow cells transplanted from either WT (WT(WT)) or aromatase-deficient (WT(ArKO)) mice. MicroCT was acquired on lumbar vertebra to assess bone quantity and quality. WT(ArKO) animals had greater trabecular bone volume (BV/TV p = 0.002), with a higher trabecular number (p = 0.008), connectivity density (p = 0.017), and bone mineral content (p = 0.004). In cortical bone, WT(ArKO) animals exhibited smaller cortical pores and lower cortical porosity (p = 0.02). Static histomorphometry revealed fewer osteoclasts per bone surface (Oc.S/BS%), osteoclasts on the erosion surface (ES(Oc+)/BS, p = 0.04) and low number of osteoclasts per bone perimeter (N.Oc/B.Pm, p = 0.01) in WT(ArKO). Osteoblast-associated parameters in WT(ArKO) were lower but not statistically different from WT(WT). Dynamic histomorphometry suggested similar bone formation indices' patterns with lower mean values in mineral apposition rate, label separation, and BFR/BS in WT(ArKO) animals. Ex vivo bone cell differentiation assays demonstrated relative decreased osteoblast differentiation and ability to form mineralized nodules. This study demonstrates a role of local 17ß-estradiol production by BMCs for regulating the quantity and quality of bone in male mice. Underlying in vivo cellular and molecular mechanisms require further study.