A fibroblast-dependent TGFß1/sFRP2 noncanonical Wnt signaling axis promotes epithelial metaplasia in idiopathic pulmonary fibrosis.

Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGFß1 signaling inhibitor, epigallocatechin gallate (EGCG), to Interstitial Lung Disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA sequencing on spare tissue. Biopsies from untreated patients showed higher fibroblast TGFß1 signaling compared to non-disease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGFß1 signaling and several pro-inflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzle-like receptor protein 2 (sFRP2), an unrecognized TGFß1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision cut lung slices (PCLS) from non-diseased donors, we found TGFß1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature Krt5+ basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGFß1 signaling in ILD, the therapeutic potential of EGCG in reducing IPF-related transcriptional changes, and identify TGFß1-non-canonical Wnt pathway crosstalk via sFRP2 as a novel mechanism for dysfunctional epithelial signaling in Idiopathic Pulmonary Fibrosis/ILD.

Psychological Resilience in Post-acute Care: A Cross-Sectional Study of Health Care Workers in Singapore Community Hospitals.

OBJECTIVES: Psychological resilience is a crucial component of mental health and well-being for health care workers. It is positively linked to compassion satisfaction and inversely associated with burnout. The current literature on health care worker resilience has mainly focused on primary care and tertiary hospitals, but there is a lack of studies in post-acute and transitional care settings. Our study aims to address this knowledge gap and evaluate the factors associated with psychological resilience among health care professionals working in community hospitals. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Physicians, nurses, rehabilitation therapists (consisting of physiotherapists, occupational therapists, and speech therapists), pharmacists, dietitians, and social workers in 2 community hospitals in Singapore. METHODS: Eligible health care workers were invited to fill in anonymous, self-reported questionnaires consisting of sociodemographic, lifestyle, and work-related factors together with the Connor-Davidson Resilience Scale (CD-RISC-10). Univariate analysis and multiple linear regression were conducted to study the relationship between each factor and resilience scores. RESULTS: A total of 574 responses were received, giving a response rate of 81.1%. The mean CD-RISC-10 score reported was 28.4. Multiple linear regression revealed that male gender (B = 1.49, P = .003), Chinese (B = -3.18, P < .001), active smokers (B = -3.82, P = .01), having perceived work crisis support (B = 2.95, P < .001), work purpose (B = 1.84, P = .002), job satisfaction (B = 1.01, P = .04), and work control (B = 2.53, P < .001) were significantly associated with psychological resilience scores among these health care workers. CONCLUSION AND IMPLICATIONS: Our study highlights the importance of certain individual and organizational factors that are associated with psychological resilience. These findings provide valuable insight into developing tailored interventions to foster resilience, such as strengthening work purpose and providing effective work crisis support, thus reducing burnout among health care workers in the post-acute care setting.

Supercharged deep inferior epigastric perforator flap for reconstruction of soft tissue defect after excision of giant invasive squamous cell carcinoma of the thigh in a refractory diabetic with Pseudomonas aeruginosa infection.

Patients with large defects after oncologic surgery often require enhanced surgical planning to optimize reconstructive outcomes. As such, medically complex patients require innovative solutions when utilizing abdominal flaps due to concern for ischemia of the distal tissue. Vascular augmentations, such as supercharging or turbocharging, serve to increase perfusion in these medical complex patients to ensure flap survival. In this report, we highlight the use of a supercharged bilateral pedicled deep inferior epigastric perforator (DIEP) flap in a patient with a 231 cm2 thigh defect in the setting of uncontrolled diabetes. A 57-year-old male with poorly-controlled diabetes (blood sugar prior to surgery 510 mg/dL) and iron deficiency anemia presented with a two-year history of a large nonmetastatic squamous cell carcinoma (SCC) measuring 19 × 9 cm2 on the right thigh. Positron emission tomography/computed tomography and biopsies of the right retroperitoneal and inguinal lymph nodes diagnosed the mass as Stage 3 localized SCC. After excision, we performed immediate reconstruction of the resultant defect with a supercharged bilateral pedicled DIEP flap. The flap was pedicled on the ipsilateral DIEP and the contralateral perforator was anastomosed to the descending branch of the lateral circumflex femoral artery (DLCFA) at the inferior aspect of the defect. A venous coupler was used for the veins and the arteries were hand-sewn in end-to-end fashion. The supercharged bilateral pedicled DIEP flap was utilized for enhanced augmented perfusion to the distal edge of the pedicled flap in a high-risk patient. The patient's clinical course was complicated by a Pseudomonas infection of a small hematoma requiring operative washout and debridement of necrotic fat. However, the flap survived and covered the defect completely. The patient required outpatient antibiotics for the Pseudomonas infection which resolved completely without further need for operative intervention. At 6-month follow up, the reconstruction was stable with no tumor recurrence on clinical exam. Our results suggest that a supercharged pedicled DIEP flap may be a viable option for large defects of the thigh and can may be utilized in medically complex patients with poor capacity for wound healing.

Novel use and utilization of robotic Hoyer-Hook system for suspension of panniculus morbidus.

Panniculus morbidus is a complication of morbid obesity characterized by massive abdominal folds that hang below the beltline. Ulceration, dermatitis, and sinus tract formation of the pannus can cause significant morbidity to the patient and impair activities of daily living. If patients fail medical management, the next step is surgical excision. Challenging aspects of the procedure include adequate suspension of the pannus, cost, and prevention of intra-abdominal injuries. We present a case of a 70-year-old female with panniculus morbidus with endometrial carcinoma. We successfully performed a panniculectomy using a novel combination of towel hooks and the Hoyer lift to suspend the abdomen. In the same anesthesia event, she underwent robotic-assisted hysterectomy. No intra-operative or post-operative complications were encountered, and the patient was satisfied with her results. In this case, we demonstrated an effective and cost-efficient approach to panniculectomy in the severely obese patient.

Non-surgical Management of Locally Advanced Basal Cell Carcinoma of the Upper Extremity With Vismodegib.

Basal cell carcinoma (BCC) is a common skin malignancy that can present reconstructive challenges in patients with locally advanced diseases of the extremities. This article highlights three cases of locally advanced BCC of the extremities managed with vismodegib (Erivedge, Genentech). Vismodegib is a sonic hedgehog pathway (Shh) inhibitor approved by the FDA for use in metastatic or recurrent BCC. All three patients in our case series demonstrated significant clinical responses with reductions in tumor size which obviated the need for complex reconstructive surgery or amputation.

Reporting errors in plain radiographs for lower limb trauma-a systematic review and meta-analysis.

INTRODUCTION: Plain radiographs are a globally ubiquitous means of investigation for injuries to the musculoskeletal system. Despite this, initial interpretation remains a challenge and inaccuracies give rise to adverse sequelae for patients and healthcare providers alike. This study sought to address the limited, existing meta-analytic research on the initial reporting of radiographs for skeletal trauma, with specific regard to diagnostic accuracy of the most commonly injured region of the appendicular skeleton, the lower limb. METHOD: A prospectively registered, systematic review and meta-analysis was performed using published research from the major clinical-science databases. Studies identified as appropriate for inclusion underwent methodological quality and risk of bias analysis. Meta-analysis was then performed to establish summary rates for specificity and sensitivity of diagnostic accuracy, including covariates by anatomical site, using HSROC and bivariate models. RESULTS: A total of 3887 articles were screened, with 10 identified as suitable for analysis based on the eligibility criteria. Sensitivity and specificity across the studies were 93.5% and 89.7% respectively. Compared with other anatomical subdivisions, interpretation of ankle radiographs yielded the highest sensitivity and specificity, with values of 98.1% and 94.6% respectively, and a diagnostic odds ratio of 929.97. CONCLUSION: Interpretation of lower limb skeletal radiographs operates at a reasonably high degree of sensitivity and specificity. However, one in twenty true positives is missed on initial radiographic interpretation and safety netting systems need to be established to address this. Virtual fracture clinic reviews and teleradiology services in conjunction with novel technology will likely be crucial in these circumstances.

PLA2 and ENPP6 may act in concert to generate phosphocholine from the matrix vesicle membrane during skeletal mineralization.

Mineralization is a key process in the formation of bone and cartilage in vertebrates, involving the deposition of calcium- and phosphate-containing hydroxyapatite (HA) mineral within a collagenous matrix. Inorganic phosphate (Pi) accumulation within matrix vesicles (MVs) is a fundamental stage in the precipitation of HA, with PHOSPHO1 being identified as the principal enzyme acting to produce Pi PHOSPHO1 is a dual-specific phosphocholine/phosphoethanolamine phosphatase enriched in mineralizing cells and within MVs. However, the source and mechanism by which PHOSPHO1 substrates are formed before mineralization have not been determined. Here, we propose that 2 enzymes-phospholipase A2 (PLA2) and ectonucleotide pyrophophatase/phosphodiesterase 6 (ENPP6)-act in sequence upon phosphatidylcholine found in MV membranes to produce phosphocholine, which PHOSPHO1 can hydrolyze to liberate Pi This hypothesis is supported by evidence that both enzymes are expressed in mineralizing cells and data showing that phosphatidylcholine is broken down in MVs during mineralization. Therefore, PLA2 and ENPP6 activities may represent a key step in the mineralization process. Further functional studies are urgently required to examine their specific roles in the initiation of skeletal mineralization.-Stewart, A. J., Leong, D. T. K., Farquharson, C. PLA2 and ENPP6 may act in concert to generate phosphocholine from the matrix vesicle membrane during skeletal mineralization.

Chondromyxoid fibroma of the sacrum: A case report and literature review.

BACKGROUND: Chondromyxoid fibroma (CMF) is an extremely rare, benign cartilaginous tumor that makes up <0.5% of all bone tumors, typically presenting in the second or third decade of life. CMF of the sacrum is exceedingly rare, with only seven documented cases reported in the neurosurgical literature. CASE DESCRIPTION: We report a case of a 35-year-old female with a 3 month history of lower back pain after sustaining a fall on her sacrum/coccyx presenting with a progressive complaint of localized lower back pain, occasional urinary retention without incontinence, gluteal hypesthesia, and pressure below the gluteal crease. Imaging demonstrated a large, expansile enhancing soft-tissue lesion involving the sacrum, distal to the S2-3 disc space. The tumor was removed with partial sacrectomy for open en bloc resection with partial nerve sparing. The patient was found at 1.5-year follow-up with the improvement of symptoms, no recurrence, and no residual neurologic dysfunction. CONCLUSION: Sacral CMF is a rare clinical entity that may mirror more aggressive sacral pathology, including chordoma, in both clinical presentation and imaging characteristics. A review of the available literature regarding diagnosis, surgical management options, and prognosis for sacral CMF is provided.

Injury and illness surveillance at the International Sailing Federation Sailing World Championships 2014.

BACKGROUND/AIM: The Sailing World Championships 2014 was contested by 1167 sailors in all 10 Olympic classes. Our objective was to characterise sailing-related injuries and illnesses in sailors participating in this regatta. METHODS: We conducted 2 surveys: (1) prior to the World Championships, sailors answered a 12-month recall questionnaire on sailing-related injuries and illnesses and (2) during the Championships, injuries and illnesses were documented. RESULTS: There were 760 respondents (65% of all participants) for the 12-month recall questionnaire (58% male, 42% female), of whom 244 participants reported 299 injuries (0.59 injuries per 1000 h of sailing). Injuries were most prevalent in the 49erFX (64%), RS:X Women (39%), 49er (37%) and Nacra 17 (36%). Lower back (29% of sailors), knee (13%), shoulder (12%) and ankle (10%) injuries were most prevalent; most (58% of all injuries) were overuse injuries; and 56% of sailors lost sailing time. Most illnesses (40%) were infections, primarily of the respiratory system (43%). During the Championships, there were 67 injuries (4 per 1000 days of sailing). The 49er (24% of all injuries), 470 Men and Women (24%), and 49erFX (19%) had the highest incidence. Injuries to the hand/fingers (22% of all injuries), back (18%), and foot (12%) were most common, as were contusions (37% of all injuries), cuts/lacerations (24%), and sprains (9%). Of the 29 illnesses (2 per 1000 days of sailing), 9 (31%) were gastrointestinal and 6 (21%) respiratory, while 2 (7%) were gout attacks. CONCLUSIONS: The Olympic classes introduced since 2000 (49erFX, 49er, Nacra 17) have resulted in a rise in injuries.

Comparison of autologous conditioned plasma injection, extracorporeal shockwave therapy, and conventional treatment for plantar fasciitis: a randomized trial.

OBJECTIVES: To evaluate the efficacy of autologous conditioned plasma (ACP) compared with extracorporeal shockwave (ESWT) and conventional treatments for plantar fasciitis. DESIGN: Randomized trial. SETTING: Sports medicine center in a tertiary care hospital. PATIENTS: Fifty-four subjects (age range, 29-71 years) with unilateral chronic plantar fasciitis with more than 4 months of symptoms. METHODS: Subjects randomized to 3 groups: 19 to ACP and conventional treatment (ACP group), 19 to ESWT and conventional treatment (ESWT group), and 16 to conventional treatment alone. Conventional treatment included stretching exercises and orthotics if indicated. MAIN OUTCOME MEASUREMENTS: Outcomes were pain-Visual Analog Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and ultrasound plantar fascia thickness assessed at baseline before treatment and at 1 month, 3 months, and 6 months after treatment. RESULTS: VAS, AOFAS ankle-hindfoot scale, and plantar fascia thickness improved in all groups. Significant VAS pain score improvements in the ACP group compared with conventional treatment at month 1 (P = .037) and for the ESWT group compared with conventional treatment at months 1, 3, and 6 (P = .017, P = .022, and P = .042). The AOFAS ankle-hindfoot scale score improved in the ACP group at months 3 and 6 (P = .004 and P = .013) and, for the ESWT group, at months 1 and 3 (P = .011 and P = .003) compared with conventional treatment. Significant improvements in plantar fascia thickness were seen in the ACP group at months 1 and 3 compared with conventional treatments (P = .015 and P = .014) and at months 3 and 6 compared with the ESWT group (P = .019 and P = .027). No adverse events reported. CONCLUSIONS: Treatment of plantar fasciitis with ACP or ESWT plus conventional treatments resulted in improved pain and functional outcomes compared with conventional treatment alone. There was no significant difference between ACP and ESWT in terms of VAS and AOFAS ankle-hindfoot scale improvements, although the ACP group demonstrated greater reductions in plantar fascia thickness.

Comparing effects of low- and high-volume moderate-intensity exercise on sexual function and testosterone in obese men.

INTRODUCTION: Obesity and inactivity are associated with erectile dysfunction and hypogonadism. AIM: To compare the effects of low volume (LV) and high volume (HV) of moderate-intensity exercise on sexual function, testosterone, lower urinary tract symptoms (LUTS), endothelial function, and quality of life (QoL) in obese men. MAIN OUTCOME MEASURES: Weight, waist circumference (WC), body composition, International Index of Erectile Function 5-item (IIEF-5), International Prostate Symptom Scale (IPSS) (for LUTS), and 36-item Short Form Survey version 2 Instrument (SF-36) (for QoL) scores, plasma testosterone, sex-hormone binding globulin, glucose, insulin and lipids, and endothelial function (by Reactive Hyperaemia Index [RHI] using finger plethysmography) were measured at baseline and 24 weeks. METHODS: Ninety abdominally obese (body mass index > 27.5 kg/m(2), WC > 90 cm), sedentary (exercise ≈ 80 minutes/week) Asian men (mean age 43.6 years, range 30-60) were prescribed a diet to reduce daily intake by ≈ 400 kcal below calculated requirement and randomized to perform moderate-intensity exercise of LV (<150 minutes/week) or HV (200-300 minutes/week) (n = 45 each) for 24 weeks. Seventy-five men (83.3%) completed the study. RESULTS: Weekly exercise volume was significantly greater in the HV (236 ± 9 minutes) than the LV (105 ± 9 minutes) group. The HV group had significantly greater increases in IIEF-5 score (2.6 ± 0.5 points) and testosterone (2.06 ± 0.46 nmol/L) and reductions in weight (-5.9 ± 0.7 kg, -6.2%), WC (-4.9 ± 0.8 cm, -4.9%), and fat mass (-4.7 ± 1.0 kg, -14.5%) than the LV group (-2.9 ± 0.7 kg, -3.0%; -2.7 ± 0.7 cm, -2.5%; -1.1 ± 0.8 kg, -3.2%; 0.79 ± 0.46 nmol/L; and 1.8 ± 0.5 points). Improvements in IPSS and SF-36 scores, and RHI, were similar. CONCLUSIONS: Moderate-intensity HV aerobic exercise > 200 minutes/week produces greater improvements in sexual function, testosterone, weight, WC, and fat mass than smaller exercise volume.

Surgical treatment of breast cancer in previously augmented patients.

The incidence of breast cancer is increasing each year. Concomitantly, cosmetic breast augmentation has become the second most often performed cosmetic surgical procedure. As the augmented patient population ages, an increasing number of breast cancer cases among previously augmented women can be anticipated. The surgical treatment of these patients is controversial, with several questions remaining unanswered. Is breast conservation therapy feasible in this patient population and can these patients retain their implants? A retrospective review of all breast cancer patients with a history of previous augmentation mammaplasty who were treated at the Revlon/UCLA Breast Center between 1991 and 2001 was performed. During the study period, 58 patients were treated. Thirty patients (52 percent) were treated with a modified radical mastectomy with implant removal. Twenty-eight patients (48 percent) underwent breast conservation therapy, which consisted of lumpectomy, axillary lymph node dissection, and radiotherapy. Twenty-two of the patients who underwent breast conservation therapy initially retained their implants. Eleven of those 22 patients (50 percent) ultimately required completion mastectomies with implant removal because of implant complications (two patients), local recurrences (five patients), or the inability to obtain negative margins (four patients). Nine additional patients experienced complications resulting from their implants, including contracture, erosion, pain, and rupture. The data illustrate that breast conservation therapy with maintenance of the implant is not ideal for the majority of augmented patients. Breast conservation therapy with explantation and mastopexy might be appropriate for rare patients with large volumes of native breast tissue. Mastectomy with immediate reconstruction might be a more suitable choice for these patients.

Restraint stress modulates brain, pituitary and adrenal expression of angiotensin II AT(1A), AT(1B) and AT(2) receptors.

Angiotensin II (Ang II) AT(1) receptors are involved in the regulation of the stress response. In adult male rats, acute restraint increased AT(1A) mRNA in paraventricular nucleus. Repeated restraint increased AT(1A) mRNA and AT(1) binding in paraventricular nucleus and AT(1) binding in subfornical organ and median eminence. AT(1B) and AT(2) receptors were not expressed in brain areas involved in the stress response. Acute restraint increased anterior pituitary AT(1A) mRNA and AT(1) binding and decreased AT(1B) mRNA. During repeated restraint, the increase in AT(1A) mRNA in the anterior pituitary was maintained, but AT(1B) mRNA and AT(1) binding returned to normal levels. In adrenal zona glomerulosa, AT(1B) mRNA, AT(1) binding, AT(2) mRNA and AT(2) binding decreased during acute restraint. Receptor mRNA and binding returned to normal after repeated stress, with the exception of rebound increase in adrenal zona glomerulosa AT(2) mRNA. In adrenal medulla, AT(1A) mRNA increased and AT(2) mRNA decreased during acute restraint. AT(1A) mRNA remained increased during repeated restraint, while alterations in AT(2) mRNA were no longer present. Expression of AT(1A), AT(1B) and AT(2) receptors in the hypothalamic-pituitary-adrenal axis is tissue specific and is different in acute and repeated stress. Increased brain, pituitary and adrenomedullary AT(1A) receptor expression correlates with hypothalamic-pituitary-adrenal axis stimulation, supporting the hypothesis of Ang II, through selective AT(1A) receptor stimulation, as an important determinant of the acute and repeated stress response. Decreased adrenal zona glomerulosa and anterior pituitary AT(1B) receptors during acute stress can be interpreted as compensatory to increased stimulation by Ang II. There may be additional roles for adrenal AT(2) receptors during acute stress, possibly related to interaction or cross-talk with AT(1) receptors.