Abstract Although the neuroprotective effects of hydrogen sulfide (H 2 S) have been demonstrated in several studies, whether H 2 S protects against early brain injury (EBI) and secondary cognitive dysfunction in subarachnoid hemorrhage (SAH) model remains unknown. This study was undertaken to evaluate the influence of H 2 S on both acute brain injury and neurobehavioral changes as well as the underlying mechanisms after SAH. The H 2 S donor, NaHS, was administered via an intraperitoneal injection at a dose of 5.6 mg/kg at 2 h, 6 h, 24 h, and 46 h after SAH in rat model. The results showed that NaHS treatment significantly improved brain edema and neurobehavioral function, and attenuated neuronal cell death in the prefrontal cortex, associated with a decrease in Bax/Bcl‐2 ratio and suppression of caspase‐3 activation at 48 h after SAH. NaHS also promoted phospho‐Akt and phospho‐ERK levels. Furthermore, NaHS treatment significantly enhanced the levels of brain‐derived neurotrophic factor (BDNF) and phospho‐CREB. Importantly, NaHS administration improved learning and memory performance in the Morris water maze test at 7 days post‐SAH in rats. These results demonstrated that NaHS, as an exogenous H 2 S donor, could significantly alleviate the development of EBI and cognitive dysfunction induced by SAH via Akt/ERK‐related antiapoptosis pathway, and upregulating BDNF‐CREB expression.
<p>PDF file - 126KB, mAb anti-VISTA clones GA1 and GG8 specifically bind to human VISTA. a) human PBMCs were stained with anti-CD33 and anti-VISTA clone GA1 (red and blue) or isotype control (grey). Blocking VISTA-Ig was included in one sample to show specificity (red). Representative overlays show live, large scatter, singlet, CD33 positive events from at least two separate donors. b) K562 cells transduced with human VISTA (red) or parent K562 cells (grey) were stained with anti-VISTA clone GA1. Representative overlays show live, singlet events. c) consecutive sections of human splenic tissues were stained with anti-VISTA clone GG8 and/or Blocking VISTA-Ig. A pre-incubation step with Fc Receptor Blocking Solution (Human TruStain FcX, BioLegend) was included in some tissue samples as indicated.</p>
To investigate the relationship of verumontanum hypertrophy with chronic prostatitis.Fifty-two patients with chronic prostatitis underwent cystourethroscopy for comparing the size of the verumontanum before and after treatment.Before treatment, all the patients showed different degrees verumontanum hypertrophy, of whom 50 were treated by conventional drug therapy, and the other 2 with voiding dysfunction by drug therapy combined with transurethral resection. Cystourethroscopy revealed significantly decreased size of the verumontanum in 44 of the patients after treatment (P < 0.05).Patients with chronic prostatitis often have verumontanum hypertrophy, which could be an indicator of the effect of treatment.
Reactive perforating collagenosis (RPC) is a cutaneous disorder that has rarely been associated with haematological malignancies. We present the case of a 47-year-old man with a 6-month history of Epstein–Barr virus-positive angioimmunoblastic T-cell lymphoma (AITL) who was undergoing chemotherapy and had an extremely pruritic, papular eruption that had worsened over the past 7 months. Skin biopsy findings revealed RPC. He was treated with triamcinolone cream and hydroxyzine alongside his chemotherapy; this resolved his symptoms. This patient’s case offers a unique clinicopathological presentation of RPC in the setting of AITL in the skin and demonstrates the importance of a dermatologist's management of cutaneous disorders in patients with cancer to improve their quality of life.
BACKGROUND Early therapies for metastatic melanoma improved patient quality of life; however, median survival remained unaffected. Studies are showing that surgical excision with the combination of immune checkpoint inhibitor (ICI) therapy has better outcomes than systemic therapy alone. This single-center case series describes 7 patients with oligometastatic melanoma treated by metastasectomy in combination with ICI and BRAF inhibitors. CASE REPORT One female and 6 male patients are included in our study, with ages ranging from 34 to 82 years. Oligometastatic melanoma is defined was having no more than 5 metastatic regions. Each patient had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received either ICI therapy with ipilimumab, nivolumab, and/or pembrolizumab, or targeted therapy with encorafenib and binimetinib, or a combination. Patients underwent metastasectomies with curative intent. The main outcome and measurements obtained were the duration of disease-free survival, based on radiographic evidence. The range of disease-free survival in our population was 13 to 67 months, with the lower end limited by patient death and the upper limit being the present day. CONCLUSIONS This case series reiterates survival benefit for patients who received metastasectomy after exhibiting good response to ICI therapy. ICI and/or BRAF inhibitor therapy combined with metastasectomy provides a possible curative option for patients who may have previously been relegated to palliative-focused care. By using a multimodal approach with oncologists and surgeons, we can challenge our understanding of what constitutes a resectable cancer.
Cutaneous squamous cell carcinoma (SCC) is a growing public health problem in the United States. A subset of high-risk SCC exhibits a more aggressive clinical trajectory including increased local recurrence and lymph node metastasis. However, there are no universally accepted criteria to help define and manage these patients. This review provides an overview of the high-risk features of cutaneous SCC, prognostic stratification of various staging systems and treatment options. It further examines the prognostic factors influencing the staging of cutaneous head and neck SCC.
Undifferentiated melanoma should be considered in the differential diagnosis of sarcomatoid cutaneous malignancies to ensure that patients receive the correct treatment. Dermatopathologists should recognize the pitfalls of relying too heavily on immunohistochemistry to establish this diagnosis and consider ancillary tests, including single-nucleotide polymorphism (SNP) copy number arrays and targeted next-generation sequencing (NGS), when a definitive diagnosis cannot be rendered on a primary or metastatic tumor. This technology can also help to exclude a collision of melanoma and sarcoma when both differentiated and undifferentiated components are juxtaposed. We describe an exceedingly rare, illustrative example of undifferentiated sarcomatoid melanoma presenting as a pedunculated nodule. The clinical context and presence of a small differentiated component helped to establish the diagnosis; however, the transition from differentiated to undifferentiated melanoma was accompanied by an abrupt loss of S100, Sox10, MITF, MelanA, and HMB45 with gain of CD10 and p63 staining. SNP copy number array and NGS revealed shared chromosomal copy number changes and overlapping mutations with additional aberrances detected exclusively in the sarcomatoid component, thereby excluding a collision tumor and confirming our putative impression of melanoma with progression to an undifferentiated sarcomatoid phenotype.
OBJECTIVE To explore the clinical effects of posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kummell disease with kyphosis. METHODS Twenty-four patients with Kummell disease complicated with kyphosis treated by posterior short-segment pedicle screw internal fixation combined with vertebroplasty from January 2016 to December 2018 were retrospectively analyzed, including 6 males and 18 females, aged 63 to 85 (73.1±6.5) years old. The clinical effect was evaluate by visual analogue scale (VAS), Oswestry Disability Index (ODI), the anterior height of injured vertebral body, and the sagittal Cobb angle of the affected segment beforeoperation, at 3 days and final follow up after operation. And the surgical complications were observed. RESULTS All 24 patients were followed up from 12 to 24 months with an average of (15.5±3.2) months. The VAS score was decreased from 5.21±1.06 preoperatively to 2.38±0.58 at 3 days postoperatively and 1.71±0.75 at final follow-up;ODI was decreased from (50.4±13.5)% preoperatively to (20.9±8.0)% at 3 days postoperatively and (16.7±9.6)% at final follow-up;the anterior height of injured vertebral body was restored from (8.0±4.2) mm before surgery to (18.1±5.0) mm at 3 days after surgery and (16.8±5.1) mm at final follow up;the sagittal Cobb angle of affected segment was decreased from (19.5±6.3)° preoperatively to (7.6±2.1)° at 3 days after surgery and(8.4±1.7)° at final follow-up. VAS, ODI, anterior height of injured vertebral body, and sagittal Cobb angle of affected segment were significantly improved at 3 days after operation and at final follow-up (P<0.05). Two patients had complications, including asymptomaticcement leakage in 1 patient and superficial wound infection in 1 patient. CONCLUSION Posterior short-segment pedicle screw internal fixation combined with vertebroplasty for the treatment of Kummell disease with kyphosis has relatively small surgical trauma, excellent clinical results, good vertebral height recovery, satisfactory correction of kyphotic angle, and fewer complications, etc. It is a safe and effective surgical method to treat Kummell disease with kyphosis.
A 24‐year‐old female with a lifelong history of neurofibromatosis type 1 presented with left ring finger pain and decreased sensation for over a year. She has multiple café au lait spots over her entire trunk, upper and lower extremities. She also had 11 surgeries to excise superficial neurofibromas over her body. She first noticed a painful swelling of the proximal phalanx of the left ring finger. She then gradually noticed a loss of sensation distally and a constant numb and tingling feeling distal to the palm and the left ring finger. The clinical impression was neurofibroma. MRI of the tender lesion found no evidence of neurofibroma. Biopsy of the lesion showed hypertrophy of Pacinian Corpuscles. Hypertrophy of Pacinian Corpuscles is a rare condition which has been reported very infrequently. It should be considered in the differential diagnosis of any patient with persistent pain localized to the distal palm or digits in addition to glomus tumor and neuroma. It was thought not to be connected with neurofibromatosis. The finding of this lesion in a patient with neurofibromatosis is somewhat intriguing and the relationship of these two entities is unclear.
Glioblastoma multiforme (GBM) is one of the utmost malignant tumors. Excessive angiogenesis and invasiveness are the major reasons for their uncontrolled growth and resistance toward conventional strategies resulting in poor prognosis. In this study, we found that low-dose JSI-124 reduced invasiveness and tumorigenicity of GBM cells. JSI-124 effectively inhibited VEGF expression in GBM cells. In a coculture study, JSI-124 completely prevented U87MG cell–mediated capillary formation of HUVECs and the migration of HUVECs when cultured alone or cocultured with U87MG cells. Furthermore, JSI-124 inhibited VEGF-induced cell proliferation, motility, invasion and the formation of capillary-like structures in HUVECs in a dose-dependent manner. JSI-124 suppressed VEGF-induced p-VEGFR2 activity through STAT3 signaling cascade in HUVECs. Immunohistochemistry analysis showed that the expression of CD34, Ki67, p-STAT3 and p-VEGFR2 protein in xenografts was remarkably decreased. Taken together, our findings provide the first evidence that JSI-124 effectively inhibits tumor angiogenesis and invasion, which might be a viable drug in anti-angiogenesis and anti-invasion therapies.
