Citations

Coccidioidomycosis is an invasive fungal infection caused by the inhalation of aerosolized spores of Coccidioides spp., which reside in the arid soil of the southwestern United States and northern Mexico. The primary infection occurs in the lungs; however, less than 40% of patients are symptomatic. Dissemination of coccidioidomycosis is rare (1-5%), but can lead to extra pulmonic disease involving any organ. Skeletal coccidioidomycosis occurs in 10% to 50% of disseminated infections. Skeletal coccidioidomycosis is a chronic and progressive infection that eventually results in bone destruction and loss of function and often involves adjacent structures such as joints, muscles, tendons and other soft tissues. This infection is frequently multifocal with axial skeletal involvement. Although radiographs and other imaging methods identify relevant abnormalities, histopathologic examination with culture of the involved bone is the only means to confirm the diagnosis. Serologic testing is adjunctive, and complement fixation titers can be evaluated serially to assess response to treatment. Skeletal coccidioidomycosis is difficult to treat, and a combination of medical therapy and surgical debridement often is needed. Early diagnosis and treatment are critical to avoid long-term problems.

* There are limited motion-sparing salvage options for patients with pancarpal wrist arthritis. Total wrist arthroplasty is one option that has long been used in an attempt to preserve motion while relieving pain and wrist dysfunction; however, enthusiasm for the procedure has been tempered by high rates of complications. * In an attempt to minimize or eliminate these complications, recent implants have been redesigned with a more semiconstrained arc of motion and ellipsoidal articulation. Furthermore, the distal component has undergone many different modifications to improve bone growth into the implant. * Short-term small series have shown promising improvements in terms of the rate of complications as compared with previous-generation designs.

ABSTRACT High-fat diet (HFD)-fed mouse models have been widely used to study early type 2 diabetes. Decreased β-cell glucokinase (GCK) expression has been observed in HFD-induced diabetes. However, owing to its crucial roles in glucose metabolism in the liver and in islet β-cells, the contribution of decreased GCK expression to the development of HFD-induced diabetes is unclear. Here, we employed a β-cell-targeted gene transfer vector and determined the impact of β-cell-specific increase in GCK expression on β-cell function and glucose handling in vitro and in vivo. Overexpression of GCK enhanced glycolytic flux, ATP-sensitive potassium channel activation and membrane depolarization, and increased proliferation in Min6 cells. β-cell-targeted GCK transduction did not change glucose handling in chow-fed C57BL/6 mice. Although adult mice fed a HFD showed reduced islet GCK expression, impaired glucose tolerance and decreased glucose-stimulated insulin secretion (GSIS), β-cell-targeted GCK transduction improved glucose tolerance and restored GSIS. Islet perifusion experiments verified restored GSIS in isolated HFD islets by GCK transduction. Thus, our data identify impaired β-cell GCK expression as an underlying mechanism for dysregulated β-cell function and glycemic control in HFD-induced diabetes. Our data also imply an etiological role of GCK in diet-induced diabetes. This article has an associated First Person interview with the first author of the paper.

We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer of basal cells. These lesions shared some histologic features with the recently described entity of ciliated muconodular papillary tumor (CMPT); however, the majority did not fit all diagnostic criteria in that they exhibited only focal or absent papillary architecture, and they had variable number of ciliated and mucinous cells, with some lesions entirely lacking 1 or both of these components. The morphologic and immunohistochemical features ranged from those resembling proximal bronchioles (proximal-type: moderate to abundant mucinous and ciliated cells; negative or weak TTF1 in luminal cells; n=8) to those resembling respiratory bronchioles (distal-type: scant or absent mucinous and ciliated cells; positive TTF1 in luminal cells; n=17). The hallmark of all lesions was a continuous layer of basal cells (p40 and CK5/6-positive). We provisionally designated these lesions as bronchiolar adenomas (BAs) and analyzed their clinicopathologic and molecular features. All BAs were discrete, sharply circumscribed lesions with a median size of 0.5 cm (range, 0.2 to 2.0 cm). Most lesions were either entirely flat (n=14) or contained focal papillary architecture (n=7); only 4 lesions, all proximal-type, were predominantly papillary, fitting the classic description of CMPT. Notably, of 9 lesions submitted for frozen section evaluation, 7 were diagnosed as adenocarcinoma. No postsurgical recurrences were observed for any lesions (median follow-up, 11 mo). Twenty-one BAs underwent next-generation sequencing and/or immunohistochemistry for BRAF V600E, revealing mutation profiles similar to those previously described for CMPTs, including BRAF V600E mutations (n=8, 38%), unusual EGFR exon 19 deletions (n=2, 10%), EGFR exon 20 insertions (n=2, 10%), KRAS mutations (n=5, 24%), and HRAS mutations (n=1, 5%). The mutation profiles were similar in proximal-type and distal-type lesions. In conclusion, we describe a family of putatively benign clonal proliferations with a spectrum of morphology recapitulating various levels of the bronchiolar tree, of which only a minor subset fits the classic description of CMPT. Comparable mutation profiles and partially overlapping morphologic features across the spectrum of these lesions support their nosological relationship. We propose designating this entire family of lesions as BAs, and that lesions currently designated CMPTs represent a subgroup of this family.

Abstract BACKGROUND The optimal diagnostic evaluation for patients with angiographically negative subarachnoid hemorrhage (AN-SAH) remains controversial. OBJECTIVE To assess the utilization rate and diagnostic yield of imaging tests routinely obtained in identifying a structural cause for AN-SAH. METHODS In this retrospective multicenter study, consecutive adult patients admitted with nontraumatic, AN-SAH between 01/2010 and 12/2015 were included. Patients with intraparenchymal, subdural, or epidural hematomas in addition to SAH were excluded. Outcomes studied included utilization rate, diagnostic yield, and median time from admission for the following imaging tests: initial computed tomography angiography (CTA) and digital subtraction angiography (DSA), brain and cervical spine magnetic resonance imaging (MRI), and any repeat DSA or CTA performed either during initial admission or at long-term follow-up. RESULTS A total of 752 patients were included (mean age, 53 yr; 54% male). Initial CTA and DSA were performed in 89% and 100% of patients, respectively. Brain MRI was performed in 75% of patients and was positive in 0.7% of cases. Cervical spine MRI was performed in 61% of patients and was positive in 0.2% of cases. Repeat, same-admission follow-up DSA and CTA were performed in 48% and 51% of patients and were positive in 3.3% and 1% of cases, respectively. Delayed follow-up DSA and CTA after discharge were performed in 26% and 7% of patients and were positive in 2% and 3.7% of cases, respectively, all with negative prior imaging studies. CONCLUSION Cervical spine and brain MRI have extremely low diagnostic yield, both are commonly utilized in patients with AN-SAH; while repeat DSA and CTA are utilized less commonly and have slightly higher diagnostic yield.

Abstract In this Technical Note, we describe an arthroscopic remplissage procedure to treat anterior instability. Specifically, we use a technique to perform double‐pulley capsulotenodesis of the infraspinatus tendon using a Knotless SutureTak Suture Anchor (Arthrex, Naples, FL). This is a modification of a previously described double‐pulley technique. The primary advantage of our technique compared with the previous double‐pulley techniques described is that knot tying is not required. Technique Video video See video under supplementary data.