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.

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.

Current and potential roles of immuno-PET/-SPECT in CAR T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapies have evolved as breakthrough treatment options for the management of hematological malignancies and are also being developed as therapeutics for solid tumors. However, despite the impressive patient responses from CD19-directed CAR T-cell therapies, ~ 40%-60% of these patients' cancers eventually relapse, with variable prognosis. Such relapses may occur due to a combination of molecular resistance mechanisms, including antigen loss or mutations, T-cell exhaustion, and progression of the immunosuppressive tumor microenvironment. This class of therapeutics is also associated with certain unique toxicities, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other "on-target, off-tumor" toxicities, as well as anaphylactic effects. Furthermore, manufacturing limitations and challenges associated with solid tumor infiltration have delayed extensive applications. The molecular imaging modalities of immunological positron emission tomography and single-photon emission computed tomography (immuno-PET/-SPECT) offer a target-specific and highly sensitive, quantitative, non-invasive platform for longitudinal detection of dynamic variations in target antigen expression in the body. Leveraging these imaging strategies as guidance tools for use with CAR T-cell therapies may enable the timely identification of resistance mechanisms and/or toxic events when they occur, permitting effective therapeutic interventions. In addition, the utilization of these approaches in tracking the CAR T-cell pharmacokinetics during product development and optimization may help to assess their efficacy and accordingly to predict treatment outcomes. In this review, we focus on current challenges and potential opportunities in the application of immuno-PET/-SPECT imaging strategies to address the challenges encountered with CAR T-cell therapies.

Omental Hibernoma Revealed by 18 F-FDG PET/CT.

ABSTRACT: Hibernomas are "pseudolipomas" originating from remnants of fetal brown adipose tissue. These rare benign tumors may occur throughout the body but most commonly in the thigh, shoulder, back, and neck, and are rarely found in the abdominal cavity, retroperitoneum, breast, bones, scrotum, and perirectum. We present a case of a 58-year-old woman with a known mediastinal mass, who was incidentally found to have a very FDG-avid fat-containing lesion in the omentum abutting the stomach. Subsequent endoscopic ultrasound-guided fine-needle aspiration confirmed hibernoma. The review of the literature shows the location is very unusual.

Androgen Deprivation Therapy Differentially Impacts Bone and Muscle in the Short Term in Physically Active Men With Prostate Cancer.

Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) therapy. Its use is associated with a loss of bone mineral density (BMD) and a greater risk of falls and osteoporotic fractures. In this prospective cohort study, we examined the impact of ADT on muscle and bone strength in men initiating ADT for PCa. Participants were evaluated at three time points: immediately before (week 0), and 6 and 24 weeks after ADT initiation. Study measures included fasting blood levels (for markers of muscle and bone metabolic activity), MRI and QCT imaging (for muscle fat content, and bone density and architecture), and validated clinical tests of muscle strength and gait. Sixteen men completed all study visits. At baseline and throughout the study, participants exercised a median of four times/week, but still experienced weight gain (+2.0 kg at week 24 versus week 0, p = 0.004). Biochemically, all men sustained dramatic early and persistent reductions in sex hormones post-ADT, along with a progressive and significant increase in serum C-telopeptide of type I collagen (CTX, +84% at week 24 versus week 0). There was a trend for rise in serum sclerostin (p = 0.09) and interleukin 6 (IL-6) (p = 0.08), but no significant change in serum myostatin (p = 0.99). Volumetric BMD by QCT declined significantly at the femoral neck (-3.7% at week 24 versus week 0), particularly at the trabecular compartment. On MRI, there were no significant changes in thigh muscle fat fraction. On physical testing, men developed weaker grip strength, but experienced no worsening in lower extremity and lumbar spine muscle strength, or on functional tests of gait. In conclusion, in physically active men, ADT for 24 weeks results in a significant increase in bone resorption and reduction in BMD, but nonsignificant changes in thigh muscle quality (on imaging) or strength and gait (on functional testing). © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A renal cell carcinoma tumorgraft platform to advance precision medicine.

Renal cell carcinoma (RCC) encompasses a heterogenous group of tumors, but representative preclinical models are lacking. We previously showed that patient-derived tumorgraft (TG) models recapitulate the biology and treatment responsiveness. Through systematic orthotopic implantation of tumor samples from 926 ethnically diverse individuals into non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice, we generate a resource comprising 172 independently derived, stably engrafted TG lines from 148 individuals. TG lines are characterized histologically and genomically (whole-exome [n = 97] and RNA [n = 102] sequencing). The platform features a variety of histological and oncogenotypes, including TCGA clades further corroborated through orthogonal metabolomic analyses. We illustrate how it enables a deeper understanding of RCC biology; enables the development of tissue- and imaging-based molecular probes; and supports advances in drug development.

68Ga-DOTATATE PET/CT Uptake in Prostate With an Incidental Finding of Prostatic Acinar Adenocarcinoma and Metastatic Neuroendocrine Cancer to the Liver.

ABSTRACT: A 69-year-old man with history of metastatic neuroendocrine tumor presented for initial staging with 68Ga-DOTATE PET/CT. 68Ga-DOTATATE PET/CT showed incidental focal increased DOTATATE uptake in the left apical prostate tissue, which was thought to be of benign etiology. Digital rectal examination later was consistent with a palpable nodule along with elevated prostate-specific antigen of 7.0 ng/mL. MRI of prostate demonstrated a 3.8-cm lesion followed by a targeted biopsy that revealed prostatic acinar adenocarcinoma. Chronic inflammatory cell infiltrates were also noted on biopsy, and this may have been the cause of increased DOTATATE uptake seen on 68Ga-DOTATATE PET/CT study.

Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT.

Copper-67 (t1/2 = 2.58 days) decays by ß- ([Formula: see text]: 562 keV) and γ-rays (93 keV and 185 keV) rendering it with potential for both radionuclide therapy and single-photon emission computed tomography (SPECT) imaging. Prompted by the recent breakthrough of 67Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of 67Cu has been rekindled. This work addresses the practicability of developing 67Cu-labeled antibodies with substantially improved quality for cancer radioimmunotheranostics. Proof of concept is demonstrated with pertuzumab, a US-FDA-approved monoclonal antibody for combination therapies of HER2-positive breast cancer. With an average number of 1.9 chelators coupled to each antibody, we achieved a two-order of magnitude increase in radiolabeling efficiency compared to literature reports. In a preclinical therapeutic study, mice (n = 4-7/group) bearing HER2+ xenografts exhibited a 67Cu-dose dependent tumor-growth inhibition from 67Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with 67Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with 67Cu radiopharmaceuticals was tested after 67Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with 67Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use 67Cu radioimmunoconjugates for cancer radioimmunotheranostics.

Quantitative CT Detects Undiagnosed Low Bone Mineral Density in Oncologic Patients Imaged With 18F-FDG PET/CT.

PURPOSE: We assessed the prevalence of low bone mineral density (BMD) in oncologic patients undergoing F-FDG PET/CT. PATIENTS AND METHODS: This is a retrospective analysis of 100 patients who underwent F-FDG PET/CT at a single center from October 2015 till May 2016. Quantitative CT (QCT) was used to assess BMD at the lumbar spine (BMDQCT) and femoral necks (BMDCTXA). SUVmax was used to evaluate metabolic activity of the bone marrow. Risk of osteoporosis-related fractures was calculated with femoral neck BMDCTXA and the FRAX algorithm, which was compared against measurements of CT attenuation of the trabecular bone at L1 (L1HU). RESULTS: Osteoporosis and osteopenia were respectively present in 16% and 46% of patients 50 years and older. Bone marrow SUVmax was correlated with BMD at the lumbar spine (ρ = 0.36, P < 0.001). Increased age and low marrow SUVmax were associated with low BMDQCT at the lumbar spine (both P < 0.001), whereas increased age, female sex, and low marrow SUVmax were associated with low BMDCTXA at the femoral necks (P < 0.001, P < 0.001, P = 0.01, respectively). L1HU had an area under the curve of 0.95 (95% confidence interval [CI], 0.90-0.99) for detecting increased risk for osteoporosis-related fracture, with best threshold of 125.8 HU (95% CI, 115.7-144.9) yielding sensitivity of 100% (95% CI, 0.92-1.00), specificity of 0.90 (95% CI, 0.76-0.97), and accuracy of 0.91 (95% CI, 0.79-0.97). CONCLUSIONS: Low BMD is frequent in oncologic patients undergoing F-FDG PET/CT. Decreased F-FDG avidity of the bone marrow correlates with decreased BMD, validating the link between osteoporosis and bone marrow fat. L1HU could be a simple and accurate approach for detecting patients at risk for osteoporosis-related fractures using PET/CTdata.

Clinical Characteristics of 3 Patients Infected with COVID-19: Age, Interleukin 6 (IL-6), Lymphopenia, and Variations in Chest Computed Tomography (CT).

BACKGROUND COVID-19 has been identified as the cause of the large outbreak of pneumonia in patients in Wuhan with shared history of exposure to the Huanan seafood market; however, there is more to learn about this disease. Some experts report that the virus may have reduced toxicity during transmission, but others say that toxicity does not change during transmission. CASE REPORT In this case series, we report clinical and imaging characteristics of 3 patients (A, B, and C) infected with COVID-19. In an exposure-tracking epidemiological investigation, we found that it is possible that Patient A transmitted the infection to her treating physician, Patient B. Patient B then likely transmitted the infection to her family member, Patient C. From the chest CT studies and clinical characteristics, we postulate that the virulence did not decrease during human-to-human transmission. In previous studies, patients with the virus infection had changes in chest CT; however, we found that during the early stages of this disease, some patients (Patient C) may have normal chest CT scans and laboratory studies. Most importantly, we found that IL-6 levels were highest and lymphocyte count was lowest in those with more severe infection. CONCLUSIONS In this case series, we report the exposure relationship of the 3 patients and found that chest CT scans may not have any changes at the beginning of this disease. Lymphopenia and elevated levels of IL-6 can be found after infection.

Does negative pressure wound therapy with irrigation improve clinical outcomes? A randomized clinical trial in patients with diabetic foot infections.

AIM: To compare the efficacy of Negative Pressure Wound Therapy (NPWT) with and without irrigation with 0.1% polyhexanide-betaine. METHODS: We randomized 150 subjects in a 16-week RCT to compare healing in patients with diabetic foot infections. NPWT delivered at 125 mm Hg continuous pressure. NPWT-I were administered at 30 cc per hour. RESULTS: There were no differences clinical treatment or outcomes: wound area after surgery (18.5 ± 19.0 vs. 13.4 ± 11.1 cm2, p = 0.50), duration of antibiotics (39.7 ± 21.0 vs. 38.0 ± 24.6 days, p = 0.40), number of surgeries (2.3 ± 0.67 vs. 2.2 ± 0.59, p = 0.85), duration of NPWT (148.1 ± 170.4 vs. 114.5 ± 135.1 h, p = 0.06), healed wounds (58.7% vs. 60.0%, p = 0.86), time to healing (56.3 ± 31.7 vs. 50.7 ± 27.8, p = 0.53), length of stay (13.8 ± 6.4 vs. 14.5 ± 11.2 days, p = 0.42), re-infection (20.0% vs. 22.7%, p = 0.69, and re-hospitalization (17.3% vs. 18.7, p = 0.83). CONCLUSIONS: The addition of irrigation to NPWT did not change clinical outcomes in patients with diabetic foot infections. CLINICAL TRIAL NUMBER: NCT02463487, ClinicalTrials.gov.

Clinical Outcomes of Foot Infections in Patients Without Diabetes.

The aim of this study was to report clinical outcomes of moderate and severe foot infections in patients without diabetes. Medical records of 88 nondiabetic patients with foot infections treated at a safety net hospital were retrospectively reviewed. Patients were grouped by the presence of soft-tissue infection (STI) or osteomyelitis (OM). The diagnosis of OM was determined by positive bone culture or histopathology. STIs were defined by negative bone biopsy or negative imaging with magnetic resonance imaging or computed tomography/dual-modality radiolabeled white blood cell single-photon emission computed tomography. Patient outcomes were recorded ≤1 year after admission. Eighty-eight nondiabetic patients admitted to our institution for moderate or severe foot infections were included, 45 OM and 43 STI. No differences were noted in patient characteristics except that OM patients had a higher prevalence of neuropathy (66.7% versus 39.5%, p = .02). OM patients required surgery more often (97.8% versus 67.4%, p < .01), a greater number of surgeries (2.0 ± 1.2 versus 1.4 ± 1.3, p = .02), and more amputations (75.6% versus 11.6%, p < .01) than STI patients. OM patients had a higher proportion of wounds that healed (82.2% versus 62.8%, p = .04). There were no significant differences in reinfection (35.6% versus 25.6%, p = .36), foot-related readmission to hospital (35.6% versus 23.3%, p = .25), or total duration of antibiotics (13.9 ± 10.2 versus 13.5 ± 12.9, p = .87) between OM and STI patients. In conclusion, OM patients required more surgeries and amputations than patients with STIs; however, they had similar rates of reinfection and readmission within a year after the index hospitalization.

Aromatase deficiency in hematopoietic cells improves glucose tolerance in male mice through skeletal muscle-specific effects.

Estrogens are important for maintaining metabolic health in males. However, the key sources of local estrogen production for regulating energy metabolism have not been fully defined. Immune cells exhibit aromatase activity and are resident in metabolic tissues. To determine the relative contribution of immune cell-derived estrogens for metabolic health in males, C57BL6/J mice underwent bone marrow transplant with marrow from either wild-type (WT(WT)) or aromatase-deficient (WT(ArKO)) donors. Body weight, body composition, and glucose and insulin tolerance were assessed over 24 weeks with mice maintained on a regular chow diet. No differences were found in insulin sensitivity between groups, but WT(ArKO) mice were more glucose tolerant than WT(WT) mice 20 weeks after transplant, suggestive of enhanced glucose disposal (AUCglucose 6061±3349 in WT(WT) mice versus 3406±1367 in WT(ArKO) mice, p = 0.01). Consistent with this, skeletal muscle from WT(ArKO) mice showed higher expression of the mitochondrial genes Ppargc1a (p = 0.03) and Nrf1 (p = 0.01), as well as glucose transporter type 4 (GLUT4, Scl2a4; p = 0.02). Skeletal muscle from WT(ArKO) mice had a lower concentration of 17ß-estradiol (5489±2189 pg/gm in WT(WT) mice versus 3836±2160 pg/gm in WT(ArKO) mice, p = 0.08) but higher expression of estrogen receptor-α (ERα, Esr1), raising the possibility that aromatase deficiency in immune cells led to a compensatory increase in ERα signaling. No differences between groups were found with regard to body weight, adiposity, or gene expression within adipose tissue or liver. Immune cells are a key source of local 17ß-estradiol production and contribute to metabolic regulation in males, particularly within skeletal muscle. The respective intracrine and paracrine roles of immune cell-derived estrogens require further delineation, as do the pathways that regulate aromatase activity in immune cells specifically within metabolic tissues.

The Infected Diabetic Foot: Re-evaluating the Infectious Diseases Society of America Diabetic Foot Infection Classification.

BACKGROUND: We provide evidence to revise the Infectious Diseases Society of America (IDSA) diabetic foot infection classification by adding a separate tier for osteomyelitis and evaluating if moderate and severe infection criteria improve the classification's ability to direct therapy and determine outcomes. METHODS: We retrospectively evaluated 294 patients with moderate and severe infections. Osteomyelitis was confirmed by bone culture or histopathology. Soft tissue infection (STI) was based on negative bone culture, magnetic resonance imaging, or single-photon emission computed tomography. We stratified STI and osteomyelitis using IDSA criteria for moderate and severe infections and compared outcomes and complications. RESULTS: Osteomyelitis patients had greater antibiotic duration (32.5 ± 46.8 vs 63.8 ± 55.1 days; P < .01), surgery frequency (55.5% vs 99.4%; P < .01), number of surgeries (2.1 ± 1.3 vs 3.3 ± 2.3; P < .01), amputations (26.3% vs 83.4%; P < .01), reinfection (38.0% vs 56.7%; P < .01), and length of stay (14.5 ± 14.9 vs 22.6 ± 19.0 days; P < .01). There were no differences in moderate and severe STI outcomes except for infection readmissions (46.2% vs 25.0%; P = .02), and acute kidney injury (31.2% vs 50.0%; P = .03). There were no differences in moderate and severe osteomyelitis except the number of surgeries (2.8 ± 2.1 vs 4.1 ± 2.5; P < .01) and length of stay (18.6 ± 17.5 vs 28.2 ± 17.7; P < .01). CONCLUSIONS: The IDSA classification better reflects outcomes if risk categories are stratified by STI or osteomyelitis and moderate and severe infections are not categorized separately.

The role of estrogens in the adipose tissue milieu.

One of the leading causes for the development of adverse metabolic effects, including type 2 diabetes, dyslipidemia, and cardiovascular diseases, is the accumulation of excess body weight, often measured by body mass index (BMI). Although BMI, calculated using weight and height, is the standard measure used to determine body adiposity in clinical and public health guidelines, an inherent limitation is that BMI does not distinguish where in the body adiposity is deposited. Central obesity, characterized by greater accumulation of adiposity in the abdominal region, has been associated with a higher risk of mortality, independent of BMI. Importantly, one of the determinants of body fat distribution is sex hormones. Both estrogens and androgens appear to directly and indirectly influence body fat distribution. Our review will focus specifically on the role of estrogens and their influence in determining body fat distribution and overall health of adipose tissues, and the role of epigenetic mechanisms in regulating the production and function of estrogens.

Randomized clinical study to compare negative pressure wound therapy with simultaneous saline irrigation and traditional negative pressure wound therapy for complex foot infections.

The aim of this study was to compare the efficacy of different negative pressure wound therapy (NPWT) devices and NPWT with and without simultaneous irrigation in patients admitted to hospital with moderate and severe foot infections. Ninety patients were randomized in a 12-week prospective, randomized noninferiority trial to compare wound healing in patients with moderate and severe infected foot wounds treated with NPWT after surgery. Inclusion criteria included ABI > 0.5 or toe pressures >30 PVR/mmHg, >18 years of age and exclusion included active Charcot arthropathy, collagen vascular disease, HIV, and hypercoagulable state. We compared two different traditional devices, NPWT-K (KCI, VAC Ulta) and NPWT-C (Cardinal, PRO), and NPWT-I with saline irrigation (Cardinal, PRO). All patients had therapy delivered at 125 mmHg continuous pressure. In patients who received simultaneous saline irrigation (NPWT-I), the administration rate was 15 ml per hour. The primary outcome was the proportion of healed wounds in 12 weeks. Secondary outcomes included surgical wound closure, number of surgeries, length of stay, and time to wound healing. Continuous data was presented as mean ± standard deviation. Analysis of variance was used to compare continuous variables and chi-square to compare dichotomous variables with an alpha of 0.05. There were no differences in outcomes among NPWT-I, NPWT-C, and NPWT-K groups in proportion of healed wounds (63.3%, 50.0%, 46.7% p = 0.39), surgical wound closure (83.3%, 80.0%, 63.3%, p = 0.15), number of surgeries (2.0 ± 0.49, 2.4 ± 0.77, 2.4 ± 0.68, p = 0.06), length of stay (16.3 ± 15.7, 14.7 ± 7.4, 15.3 ± 10.5 days, p = 0.87), time to wound healing (46.2 ± 22.8, 40.9 ± 18.8, 45.9 ± 28.3 days, p = 0.78). We did not identify any significant differences in clinical outcomes or adverse events between patients treated with different NPWT devices or NPWT with and without irrigation.

Do SIRS Criteria Predict Clinical Outcomes in Diabetic Skin and Soft Tissue Infections?

The aim of this study was to assess whether systemic inflammatory response syndrome (SIRS) is correlated with outcomes in diabetic foot infections (DFIs). We retrospectively reviewed 137 diabetic patients admitted to the hospital with Infectious Diseases Society of America moderate and severe DFIs. We used SIRS criteria to define severe infection based on the presence of at least 2 of the following: heart rate >90 bpm, temperature >38°C or <36°C, respiratory rate >20 breaths per minute, and white blood cell count >12,000/mm3 or <4,000/mm3. Patients with severe DFI were significantly younger (median 49.6 versus 53.6 years, p = .04), less often had type 2 diabetes (88.6% versus 98.9%, p = .01), and less often had a history of previous amputation (15.9% versus 40.9%, p < .01). There were no differences in patients with severe infections defined by SIRS versus moderate infections in the need for surgery (47.7% versus 59.1%, p = .27), any amputation (20.5% versus 29.0%, p = .29), leg amputations (6.8% versus 7.5%, p = .88), duration of antibiotics (median ± standard deviation 34.1 ± 46.5 versus 31.9 ± 47.2 days, p = .47), or healing within 1 year (68.2% versus 66.7%, p = 1.00). Length of hospital stay was the only outcome variable that was significantly different in severe infections (median 12.7 ± 11.9 versus 7.8 ± 5.8 days, p = .02). Foot-related readmission was more common in moderate infections (46.2% versus 25.0%, p = .02). In conclusion, SIRS criteria for severe infections in diabetic patients with skin and soft tissue infections were not associated with a difference in outcomes other than longer hospital stay.

Erbium: Yttrium Aluminum Garnet Laser Accelerates Healing in Indolent Diabetic Foot Ulcers.

The objective of the study was to evaluate the effect of the erbium:yttrium aluminum garnet (YAG) laser on diabetic foot ulcers (DFUs) that had not responded to standard care. We retrospectively evaluated 22 nonhealing DFUs that received at least 4 weeks of standard wound care, demonstrated poor healing response, and subsequently were treated with an erbium:YAG laser. We measured the percent wound area reduction (PWAR) for the 4 weeks before initiating laser therapy and the PWAR for 4 weeks after the initiation of laser therapy. Erbium:YAG laser treatment consisted of 2 components: debridement and resurfacing. The laser settings were the same for all treatments. We used the paired t test to compare pretreatment with posttreatment wound area reduction. During the 4-week period before the initiation of laser therapy, the average PWAR was -33.6%. Four weeks after initiating treatment with the erbium:YAG laser, the average PWAR was 63.4% (p = .002) and 72.7% of wounds had ≥50% PWAR. By 12 weeks, 50% of wounds had healed. Erbium:YAG laser therapy accelerated DFU healing in a cohort of patients with ulcers that had been unresponsive to standard of care therapy.

Imaging Metabolically Active Fat: A Literature Review and Mechanistic Insights.

Currently, obesity is one of the leading causes death in the world. Shortly before 2000, researchers began describing metabolically active adipose tissue on cancer-surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in adult humans. This tissue generates heat through mitochondrial uncoupling and functions similar to classical brown and beige adipose tissue in mice. Despite extensive research, human brown/beige fat's role in resistance to obesity in humans has not yet been fully delineated. FDG uptake is the de facto gold standard imaging technique when studying brown adipose tissue, although it has not been rigorously compared to other techniques. We, therefore, present a concise review of established and emerging methods to image brown adipose tissue activity in humans. Reviewed modalities include anatomic imaging with CT and magnetic resonance imaging (MRI); molecular imaging with FDG, fatty acids, and acetate; and emerging techniques. FDG-PET/CT is the most commonly used modality because of its widespread use in cancer imaging, but there are mechanistic reasons to believe other radiotracers may be more sensitive and accurate at detecting brown adipose tissue activity. Radiation-free modalities may help the longitudinal study of brown adipose tissue activity in the future.