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Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

Ross, Stephen; Bossis, Anthony; Guss, Jeffrey; Agin-Liebes, Gabrielle; Malone, Tara; Cohen, Barry; Mennenga, Sarah E; Belser, Alexander; Kalliontzi, Krystallia; Babb, James; Su, Zhe; Corby, Patricia; Schmidt, Brian L
BACKGROUND: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. METHODS: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. RESULTS: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. CONCLUSIONS: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00957359.
PMCID:5367551
PMID: 27909164
ISSN: 1461-7285
CID: 2329512

Technique to Improve Tracheostomy Speaking Valve Tolerance after Head and Neck Free Flap Reconstruction

Stranix, John T; Danziger, Keri M; Dumbrava, Veturia L; Mars, Ginger; Hirsch, David L; Levine, Jamie P
Increased upper airway resistance from postoperative changes after major head and neck surgery may cause elevated transtracheal pressures and result in tracheostomy speaking valve intolerance. This may be particularly true among patients with baseline pulmonary disease. We describe a patient recovering from oral cancer resection and flap reconstruction who demonstrated prolonged ventilator dependence and tracheostomy speaking valve intolerance with abnormal tracheal manometry. We attempted to improve speaking valve tolerance through the adaptation of a valve modification intended to reduce transtracheal pressures. Drilling holes into the 1-way speaking valve allowed for excess air egress and resulted in normalization of transtracheal pressures with improved speaking valve tolerance. This 1-way speaking valve modification may serve as a simple method to allow for earlier restoration of voicing and potentially reduce the number of ventilator- dependent days in this patient population.
PMCID:5222638
PMID: 28293493
ISSN: 2169-7574
CID: 2488612

Discussion: Evaluation of the Upper Limb Lymphatic System: A Prospective Lymphoscintigraphic Study in Melanoma Patients and Healthy Controls [Comment]

Silva, Amanda K; Chang, David W
PMID: 27879603
ISSN: 1529-4242
CID: 2695092

The Effect of Osteotomy Dimension on Implant Insertion Torque, Healing Mode, and Osseointegration Indicators: A Study in Dogs

Marin, Charles; Bonfante, Estevam; Granato, Rodrigo; Neiva, Rodrigo; Gil, Luiz Fernando; Marao, Heloisa Fonseca; Suzuki, Marcelo; Coelho, Paulo G
PURPOSE: This study investigated the effect of the osteotomy diameter for implant placement torque and its effect on the osseointegration. MATERIALS AND METHODS: Eight male beagle dogs received 48 implants (3.75 mm x 10 mm) in their right and left radius, 3 implants per side and allowed to heal for 3 weeks. Three experimental groups were evaluated. Group 1: implant with an undersized osteotomy of 3.0 mm; group 2: osteotomy of 3.25 mm, and group 3: osteotomy of 3.5 mm. The insertion torque was recorded for all implants. Histological sectioning and histometric analysis were performed evaluating bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS: Implants of group 1 presented statistically higher insertion torque than those of groups 2 and 3 (P < 0.01). No differences in BIC or BAFO were observed between the groups. From a morphologic standpoint, substantial deviations in healing mode were observed between groups. CONCLUSION: Based on the present methodology, the experimental alterations of surgical technic can be clinically used with no detrimental effect over the osseointegration process.
PMID: 27513163
ISSN: 1538-2982
CID: 2213722

Impaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin

Keyes, Brice E; Liu, Siqi; Asare, Amma; Naik, Shruti; Levorse, John; Polak, Lisa; Lu, Catherine P; Nikolova, Maria; Pasolli, Hilda Amalia; Fuchs, Elaine
Aged skin heals wounds poorly, increasing susceptibility to infections. Restoring homeostasis after wounding requires the coordinated actions of epidermal and immune cells. Here we find that both intrinsic defects and communication with immune cells are impaired in aged keratinocytes, diminishing their efficiency in restoring the skin barrier after wounding. At the wound-edge, aged keratinocytes display reduced proliferation and migration. They also exhibit a dampened ability to transcriptionally activate epithelial-immune crosstalk regulators, including a failure to properly activate/maintain dendritic epithelial T cells (DETCs), which promote re-epithelialization following injury. Probing mechanism, we find that aged keratinocytes near the wound edge don't efficiently upregulate Skints or activate STAT3. Notably, when epidermal Stat3, Skints, or DETCs are silenced in young skin, re-epithelialization following wounding is perturbed. These findings underscore epithelial-immune crosstalk perturbations in general, and Skints in particular, as critical mediators in the age-related decline in wound-repair.
PMCID:5364946
PMID: 27863246
ISSN: 1097-4172
CID: 2964052

The Profunda Artery Perforator Flap Experience for Breast Reconstruction

Allen, Robert J Jr; Lee, Z-Hye; Mayo, James L; Levine, Joshua; Ahn, Christina; Allen, Robert J Sr
BACKGROUND: The profunda artery perforator flap was first introduced for breast reconstruction in 2010. In this article, the authors analyze the results of all profunda artery perforator flaps performed by their group to date. METHODS: A retrospective review was completed of consecutive profunda artery perforator flaps performed by the senior author (R.J.A.) from 2010 to 2014. Patient demographics, indications, operative techniques, flap specifics, complications, and number of operations were recorded. RESULTS: Ninety-six patients have undergone 164 profunda artery perforator flap operations for breast reconstruction since 2010. Reconstructions were performed following breast cancer management (59.5 percent), following prophylactic mastectomy for cancer risk reduction (35.7 percent), and for congenital breast deformity (4.8 percent). The average age of the patients was 48 years (range, 24 to 64 years) and their average body mass index was 22.5 kg/m. Average flap weight was 367.4 g and average pedicle length was found to be 10.2 cm. The success rate of the profunda artery perforator flap was greater than 99 percent, with a 3 percent take-back rate and only one flap loss recorded. Complications included hematoma (1.9 percent), seroma (6 percent), fat necrosis (7 percent), and donor-site infection (1.9 percent). CONCLUSIONS: The profunda artery perforator flap is an excellent option for breast reconstruction. Advantages include a reliable blood supply, long pedicle, thick donor tissue, and a favorable donor site. Currently, the profunda artery perforator flap is second only to the deep inferior epigastric artery perforator among flaps used by the authors for breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
PMID: 27391834
ISSN: 1529-4242
CID: 2287702

It's not the same thing [Editorial]

Jerrold, Laurance
PMID: 27871716
ISSN: 1097-6752
CID: 2314682

Aberrant Lower Extremity Arterial Anatomy in Microvascular Free Fibula Flap Candidates: Management Algorithm and Case Presentations

Golas, Alyssa R; Levine, Jamie P; Ream, Justin; Rodriguez, Eduardo D
An accurate and comprehensive understanding of lower extremity arterial anatomy is essential for the successful harvest and transfer of a free fibula osteoseptocutaneous flap (FFF). Minimum preoperative evaluation includes detailed history and physical including lower extremity pulse examination. Controversy exists regarding whether preoperative angiographic imaging should be performed for all patients. Elevation of an FFF necessitates division of the peroneal artery in the proximal lower leg and eradicates its downstream flow. For patients in whom the peroneal artery comprises the dominant arterial supply to the foot, FFF elevation is contraindicated. Detailed preoperative knowledge of patient-specific lower extremity arterial anatomy can help to avoid ischemia or limb loss resulting from FFF harvest. If preoperative angiographic imaging is omitted, careful attention must be paid to intraoperative anatomy. Should pedal perfusion rely on the peroneal artery, reconstructive options other than an FFF must be pursued. Given the complexity of surgical decision making, the authors propose an algorithm to guide the surgeon from the preoperative evaluation of the potential free fibula flap patient to the final execution of the surgical plan. The authors also provide 3 clinical patients in whom aberrant lower extremity anatomy was encountered and describe each patient's surgical course.
PMID: 28005769
ISSN: 1536-3732
CID: 2374522

Jaw in a Day: State of the Art in Maxillary Reconstruction

Runyan, Christopher M; Sharma, Vishal; Staffenberg, David A; Levine, Jamie P; Brecht, Lawrence E; Wexler, Leonard H; Hirsch, David L
BACKGROUND: Reconstruction of maxillary defects following tumor extirpation is challenging because of combined aesthetic and functional roles of the maxilla. One-stage reconstruction combining osseous free flaps with immediate osseointegrated implants are becoming the standard for mandibular defects, and have similar potential for maxillary reconstruction. METHODS: A woman with maxillary Ewing sarcoma successfully treated at age 9 with neoadjuvant chemotherapy, right hemimaxillectomy, and obturator prosthetic reconstruction presented for definitive reconstruction, complaining of poor obturator fit, and hypernasality. Her reconstruction was computer-simulated by a multidisciplinary team, consisting of left hemi-Lefort I advancement and right maxillary reconstruction with a free fibula flap with immediate osseointegrated implants and dental prosthesis. RESULTS: Full dental restoration, midface projection, and oral fistula corrections were achieved in 1 operative stage using this approach. CONCLUSIONS: This patient demonstrates a successful approach for maxillary reconstruction using computer-planned orthognathic surgery with free fibula reconstruction and immediate osseointegrated implants with dental prosthesis.
PMCID:5503155
PMID: 28005762
ISSN: 1536-3732
CID: 2374692

Biomechanical, Biologic, and Clinical Outcomes of Undersized Implant Surgical Preparation: A Systematic Review

Stocchero, Michele; Toia, Marco; Cecchinato, Denis; Becktor, Jonas P; Coelho, Paulo G; Jimbo, Ryo
PURPOSE: To compile the current evidence on biomechanical, biologic, and clinical outcomes of undersized surgical preparation protocols in dental implant surgery. MATERIALS AND METHODS: An electronic search using three different databases (PubMed, Web of Science, and Cochrane Library) and a manual hand search were performed including in vitro, animal, and clinical studies published prior to October 2015. Studies in which an undersized drilling protocol was compared with a nonundersized drilling protocol were included. RESULTS: From an initial selection of 1,655 titles, 29 studies met the inclusion criteria, including 14 biomechanical, 7 biologic, 6 biologic and biomechanical, and 2 clinical. Due to methodologic variation, meta-analysis was not performed. Several studies showed that implants inserted with an undersized drilling approach reached a significantly higher insertion torque value than conventional drilling in low-density substrates, while this effect is less evident if a thick cortical layer is present. Similar results in terms of boneto-implant contact (BIC) were achieved in the longer term between implants inserted with undersized and nonundersized protocols. Results in the short term were inconclusive. Clinical studies did not show negative outcomes for undersized drilling, although clinical evidence was sparse. No data are available on marginal bone loss. CONCLUSION: From the biomechanical standpoint, an undersized drilling protocol is effective in increasing insertion torque in low-density bone. Biologic response in long-term healing after undersized implant placement is comparable to that in the nonundersized surgical drilling protocol. Clinical studies indicate that performing an undersized drilling protocol on low-density bone is a safe procedure; however, more extensive studies are needed to confirm these data.
PMID: 27861649
ISSN: 1942-4434
CID: 2745932