Overnight to Outpatient: A Single Institution's Experience With Mastectomy and Reconstruction Before and After the Start of the COVID-19 Pandemic.

PURPOSE: Minimizing resource use while optimizing patient outcomes has become an ever-growing component in modern healthcare, especially in the era of COVID-19. One essential component of this is deciding whether patients need hospital admission following elective procedures. The aim of this study is to investigate operative factors and patient outcomes when mastectomies with or without reconstruction are performed as ambulatory procedures versus planned inpatient admissions. METHODS: Patient charts for those undergoing mastectomy with or without reconstruction were retrospectively analyzed ranging from March 2019 until February 2021. Factors such as demographic information, operative type, operating room time, cancer stage, total stay time in the medical environment, and postoperative complications were assessed and compared between the 2 groups. RESULTS: A total of 89 patient charts were reviewed, 46 from before the COVID-19 pandemic and 43 from after the start of the pandemic. No differences were observed in demographic factors between the 2 groups. After surgical cases resumed a significant proportion, 79%, of mastectomies with or without reconstruction were performed in the ambulatory center, versus just 2% pre-COVID-19. Similarly, of all of these cases performed, only 19% resulted in hospital admission versus the previous rate of 100% (P < 0.00001). Together, these changes resulted in a significant reduction in length of stay of 39.77 ± 19.2 hours pre-COVID-19 versus 14.81 ± 18.4 hours afterward (P < 0.00001). Unfortunately, a higher number of patients who received surgery after the start of the pandemic elected to forego immediate reconstruction 49% versus 72% (P = 0.032). Most importantly, there were no observable differences found in 7-day readmission, reoperation, or emergency department visit between groups. There was also no difference in 30-day complication rate between groups. CONCLUSIONS: Mastectomy with or without reconstruction can be safely performed in the ambulatory setting without additional risk of complications or negative patient factors. This divergence from traditional the protocol of inpatient overnight admission may contribute positively toward patient comfort, minimize the use of healthcare costs and resources, and allow for increased scheduling flexibility for patient and provider alike.

Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion.

Substance P increases CCN2 dependent on TGF-beta yet Collagen Type I via TGF-beta1 dependent and independent pathways in tenocytes.

Transforming growth factor beta 1 (TGFbeta-1) and connective tissue growth factor (CCN2) are important mediators of tissue repair and fibrosis, with CCN2 functioning as a downstream mediator of TGFß-1. Substance P (SP) is also linked to collagen production in tenocytes. A link between SP, TGFbeta-1 and CCN2 has yet to be established in tenocytes or fibrogenic processes. We sought to determine whether SP induces tenocyte proliferation, CCN2, or collagen production via TGFbeta-1 signaling or independently in rat primary tenocytes. Tenocytes were isolated from rat tendons, cultured and stimulated by SP and/or TGFbeta-1. Cultured cells expressed proteins characteristic of tenocytes (vimentin and tenomodulin) and underwent increased proliferation dose dependently after SP and TGFbeta-1 treatments, alone or combined (more than SP alone when combined). SP induced TGFbeta-1 expression in tenocytes in both dose- and time-dependent manners. SP and TGFbeta-1, alone or combined, stimulated CCN2 expression in tenocytes and their supernatants after both 24 and 48 h of stimulation; a response blocked with addition of a TGFbeta-1 receptor inhibitor. In contrast, SP potentiated collagen type I secretion by tenocytes, a response abrogated by the TGFbeta-1 receptor inhibitor after 48 h of stimulation, but not after the shorter 24 h of stimulation. Our findings suggest that both SP and TGFbeta-1 can stimulate tenocyte fibrogenic processes, albeit differently. TGFbeta-1 pathway signaling was involved in CCN2 production at all time points examined, while SP induced collagen type I production independently prior to the onset of signaling through the TGFbeta-1 pathway.

Endovascular repair of radial artery non-anastomotic pseudoaneurysm in a radial forearm free flap.

The development of pseudoaneurysm is an uncommon, life-threatening complication of head and neck microvascular surgery. Only a handful of reports have been published describing microvascular pseudoaneurysms, which usually occur at the arterial anastomosis and present as a pulsatile neck mass or as haemorrhage in case of pseudoaneurysm rupture. Management is highly variable, especially in the acute setting. In patients with pseudoaneurysm where flap inosculation is inadequate, endovascular approaches may be appropriate. In this report, we describe a ruptured distal pedicle pseudoaneurysm of a radial forearm free flap salvaged with a flow-diverting stent with complete flap survival and pedicle preservation. We demonstrate further evidence and feasibility of endovascular treatment of a non-anastomotic pseudoaneurysm arising from small vessels when parent vascular integrity is critical to flap survival.

Syndrome of the Trephined: Quantitative Functional Improvement after Large Cranial Vault Reconstruction.

BACKGROUND: Large decompressive craniectomies may be life-saving; however, they may also result in syndrome of the trephined. This postrecovery sequela is characterized by dizziness, fatigue, depression, weakness, speech slowing, gait disturbance, and impaired mentation. Because this entity is poorly understood, the authors attempted to quantify the functional improvement in patients with syndrome of the trephined after cranial vault reconstruction. METHODS: Patients with cranial vault defects (>50 cm) from trauma, meningioma, and hemorrhage were studied preoperatively and postoperatively (6 months) after cranial vault reconstruction using (1) the Cognistat Active Form and (2) the Functional Independence Measure instrument (n = 40). Cranial vault reconstructive techniques varied from split cranial bone to alloplastic implants (polyetheretherketone or titanium mesh). RESULTS: Of the 143 patients treated with decompressive craniectomies, 28 percent (n = 40) developed symptoms of syndrome of the trephined. A larger craniectomy defect size correlated with development of syndrome of the trephined. Time from craniectomy to presentation of symptoms was 4.5 months. Time from craniectomy to cranial vault reconstruction was 6.1 months. Time from cranial vault reconstruction to symptom improvement was 4.3 days. Complete functional recovery of syndrome of the trephined was seen in 70 percent. Type of cranial vault reconstruction included polyetheretherketone implant (57.5 percent), split calvarial graft (22.5 percent), and titanium mesh (20 percent), and was not a determinant of functional improvement. Cognistat assessment score noted improvement (from 38 to 69); likewise, the Functional Independence Measure measurement tool showed improvement (from 38 to 98). CONCLUSIONS: Syndrome of the trephined occurs more frequently than previously described in posttraumatic patients with large cranial vault defects. Cranial vault reconstruction leads to significant, quantifiable functional improvement in a large number of patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Development of Normal and Cleft Palate: A Central Role for Connective Tissue Growth Factor (CTGF)/CCN2.

Development of the palate is the result of an organized series of events that require exquisite spatial and temporal regulation at the cellular level. There are a myriad of growth factors, receptors and signaling pathways that have been shown to play an important role in growth, elevation and/or fusion of the palatal shelves. Altered expression or activation of a number of these factors, receptors and signaling pathways have been shown to cause cleft palate in humans or mice with varying degrees of penetrance. This review will focus on connective tissue growth factor (CTGF) or CCN2, which was recently shown to play an essential role in formation of the secondary palate. Specifically, the absence of CCN2 in KO mice results in defective cellular processes that contribute to failure of palatal shelf growth, elevation and/or fusion. CCN2 is unique in that it has been shown to interact with a number of other factors important for palate development, including bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), epidermal growth factor (EGF), Wnt proteins and transforming growth factor-ßs (TGF-ßs), thereby influencing their ability to bind to their receptors and mediate intracellular signaling. The role that these factors play in palate development and their specific interactions with CCN2 will also be reviewed. Future studies to elucidate the precise mechanisms of action for CCN2 and its interactions with other regulatory proteins during palatogenesis are expected to provide novel information with the potential for development of new pharmacologic or genetic treatment strategies for clinical intervention of cleft palate during development.

The pivotal role of CCN2 in mammalian palatogenesis.

Mammalian palatogenesis is a complex process involving a temporally and spatially regulated myriad of factors. Together these factors control the 3 vital processes of proliferation, elevation and fusion of the developing palate. In this study, we show for the first time the unequivocally vital role of CCN2 in development of the mammalian palate. We utilized CCN2 knockout (KO) mice and cranial neural crest derived mesenchymal cells from these CCN2 KO mice to investigate the 3 processes crucial to normal palatogenesis. Similar to previously published reports, the absence of CCN2 inhibits proliferation of cells in the palate specifically at the G1/S transition. Absence of CCN2 also inhibited palatal shelf elevation from the vertical to horizontal position. CCN2 KO mesenchymal cells demonstrated deficiencies in adhesion and spreading owing to an inability to activate Rac1 and RhoA. On the contrary, CCN2 KO mesenchymal cells exhibited increased rates of migration compared to WT cells. The addition of exogenous CCN2 to KO mesenchymal cells restored their ability to spread normally on fibronectin. Finally, utilizing an organ culture model we show that the palatal shelves of the CCN2 KO mice demonstrate an inability to fuse when apposed. Together, these data signify that CCN2 plays an indispensible role in normal development of the mammalian palate and warrants additional studies to determine the precise mechanism(s) responsible for these effects.