Stereotactic ablative radiotherapy before resection to avoid delay for early-stage lung cancer or oligometastases during the COVID-19 pandemic: Pathologic outcomes from the SABR-BRIDGE protocol.

BACKGROUND: During coronavirus disease 2019 (COVID-19)-related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR-BRIDGE. This study presents the preliminary surgical and pathological results. METHODS: Eligible participants from four institutions (three in Canada and one in the United States) had early-stage presumed or biopsy-proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. RESULTS: Seventy-two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3-4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well-tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID-19) and five grade 2-3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time-to-surgery was 4.5 months post-SABR (range, 2-17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months; p = .069). In the exploratory best-case scenario analysis, pCR rate does not exceed 82%. CONCLUSIONS: The SABR-BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well-tolerated. Even in the best-case scenario, pCR rate does not exceed 82%.

Limb salvage after aneurysmal degeneration of a cryopreserved vein allograft: Searching the autologous veins of the arm is worth the effort.

CLINICAL DATA: We hereby report a case of limb salvage involving a 64-year-old man who was hospitalized with ischemic foot ulcers for two months. Endarterectomy with patching and stenting of the left iliofemoral artery failed. A composite bypass of two segments of the endarterectomized superficial femoral artery and a cryopreserved saphenous vein graft was implanted one week later. On day 4 postoperatively, an infection (Staphylococcus epidermidis and Pseudomonas aeruginosa) was treated empirically with antibiotics. Four months later, the femoro-tibial bypass thrombosed and the patency was restored by thrombolysis. The aneurysmal cryopreserved vein was excised. Iterative complications followed and final success was attained after implantation of autologous cephalic and basilic veins. Four years later, this femoro-tibial is still patent. PATHOLOGICAL ANALYSES: After a gross observation, the explant was dissected and the most significant sections were processed for histology, followed by analyses in scanning electron microscopy, light microscopy and transmission electron microscopy. RESULTS: The explanted specimen showed a smooth flow surface proximally but a severe distortion distally, with an accumulation of poorly organized mural thrombi. The wall of the arterialized vein was accompanied with an important inflammatory reaction. The degradation of the collagen structure was evidenced in TEM. The fibrils of collagen were still individualized but were fragmented and did not display parallelly. The regular banding was preserved. The presence of Pseudomonas aeruginosa was shown inside the wall of the homologous vein. COMMENTS: In case of sepsis, the most aggressive antibiotic treatments cannot fully eliminate the bacteremic colonizations within the wall of an alternative conduit. The cephalic and basilic autologous veins are proved to be preferable in absence of the autologous saphenous vein. The amputation was prevented and four years later the bypass is still patent. This is an outstanding result based upon the comorbidities of the patient. The most aggressive harvesting shall be recommended. This patient represented a considerable challenge and the clinical result is highly gratifying: the search for the autologous cephalic and basilic veins proved to be worth the effort.

Diagnosis of interstitial lung diseases: from Averill A. Liebow to artificial intelligence.

Histopathologic criteria of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) were defined over the years and endorsed by leading organizations decades after Dr. Averill A. Liebow first coined the term UIP in the 1960s as a distinct pathologic pattern of fibrotic interstitial lung disease. Novel technology and recent research on interstitial lung diseases with genetic component shed light on molecular pathogenesis of UIP/IPF. Two antifibrotic agents introduced in the mid-2010s opened a new era of therapeutic approaches to UIP/IPF, albeit contentious issues regarding their efficacy, side effects, and costs. Recently, the concept of progressive pulmonary fibrosis was introduced to acknowledge additional types of progressive fibrosing interstitial lung diseases with the clinical and pathologic phenotypes comparable to those of UIP/IPF. Likewise, some authors have proposed a paradigm shift by considering UIP as a stand-alone diagnostic entity to encompass other fibrosing interstitial lung diseases that manifest a relentless progression as in IPF. These trends signal a pendulum moving toward the tendency of lumping diagnoses, which poses a risk of obscuring potentially important information crucial to both clinical and research purposes. Recent advances in whole slide imaging for digital pathology and artificial intelligence technology could offer an unprecedented opportunity to enhance histopathologic evaluation of interstitial lung diseases. However, current clinical practice trends of moving away from surgical lung biopsies in interstitial lung disease patients may become a limiting factor in this endeavor as it would be difficult to build a large histopathologic database with correlative clinical data required for artificial intelligence models.

Anesthetized Long Evans rats show similar protein expression and long-term potentiation as Fischer 344 rats but reduced short-term potentiation in motor cortex.

A number of studies describe strain-related differences in the motor behavior of rats. Inbred albino F344 rats are found to be impaired in procedural spatial learning, skilled reaching, and over ground locomotion in relation to pigmented out bred Long Evans (LE) rats. These deficits could be related to the functional differences in the motor cortex of the two strains, and the objective of the present study was to examine this hypothesis. Synaptic transmission was examined in the two rat strains, using long-term potentiation (LTP) and short-term potentiation (STP), two electrophysiological measures of neural function and learning. Field potentials were evoked in the motor cortex of anesthetized Long Evans and Fischer 344 (F344) rats in response to contralateral white matter stimulation. The main findings indicated that (1) baseline-evoked responses in the two strains was similar, indicating similar basal levels of synaptic strength, (2) LTP was induced in both strains of rats, suggesting similar synaptic efficacy in the two strains of rats, and (3) STP was enhanced in the Fischer 344 rats, suggesting differences in synaptic function. Protein expression also revealed that the two strains did not differ with respect to structural or synaptic protein expression. Thus, the two strains exhibit motor skill differences despite a great degree of physiological similarity in motor cortex. The results are discussed in relation to the greater utility of using the Long Evans rat for examining the neural basis of plasticity and models of disease, especially if motor tasks are evaluated.