Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1–positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.     

Spontaneous splenic rupture during infection of cytomegalovirus. A case report

Splenic rupture is most commonly encountered after blunt abdominal trauma. Spontaneous atraumatic splenic rupture is a rare but dramatic occurrence that is most commonly attributed to infection or neoplasia. We report the case of a 27-year-old female patient without pathological history. Admitted to the emergency department for the sudden onset of left hypochondrial pain associated with vomiting, rapidly progressing to hypovolemic shock. She had reported an influenza-like illness a week earlier for which her COVID-19 PCR was negative. Emergency abdominal ultrasound and CT-scan revealed a ruptured spleen and widespread hemorrhagic fluid in the abdomen. Exploration revealed multiple ruptures in the spleen capsule. The patient underwent splenectomy with good clinical evolution. Despite the rarity of this condition, physicians should consider the diagnosis of spontaneous non traumatic splenic rupture when encountering healthy patients presenting with nonspecific left hypochondrial abdominal pain and hypovolemia. Mortality is essentially related to the delay in diagnosis and treatment and to the severity of the underlying pathology. Treatment often consists of splenectomy.     

UV-selective organic absorbers for the cosensitization of greenhouse-integrated dye-sensitized solar cells: synthesis and computational study

Molecular cosensitization is favorable for manipulating solar radiation through the judicious choice of cosensitizers having complementary absorption spectra. For greenhouse-integrated dye-sensitized solar cells (DSCs), the manipulation of solar radiation is crucial in order to maximize the flow of photosynthetically active radiation (PAR) for the effectual photosynthetic activity of plants; meanwhile, non-PAR is utilized in agrivoltaics for generating electricity. In this study, we report the synthesis of novel four UV-selective absorbers, based on the diimide scaffold, functionalized with carboxylate and pyridyl anchoring groups, for adequate adsorption onto the TiO₂ electrode in DSC. The UV/Vis absorption spectra of the DMF solution-based free dyes were measured experimentally. Basic photophysical and energetics requirements for operating greenhouse-integrated DSCs were examined at the molecular level via (time-dependent) density functional theory-based calculations. The computational results revealed the outperformance of the biphenyldiimide-structured DI-CA1 dye, especially for maximum charge transferred to its anchor, lower thermodynamic barrier for dissociating the photogenerated exciton, largest Stokes'' shift, strong electronic coupling with TiO₂ nanoparticles, and higher degree of charge separation at the DI-CA1/TiO₂ interface. PDOS showed deeper existence for the LUMO level in the CB of TiO₂, which expedites the electron injection process. The chemical and optical compatibility of DI-CA1 were then investigated as a potential cosensitizer of a reference BTD–DTP1, a green light-absorbing dye. Considerable overlap between the fluorescence spectrum of DI-CA1 and absorption spectrum of the reference BTD–DTP1 advocated the opportunity of excitation energy transfer via the radiative trivial reabsorption mechanism, which confirms the cosensitization functionality. Energy decomposition analysis and reduced density gradient maps estimated the chemical compatibility owing to weak dispersion interactions as the dominant stabilizing attractive force. This noncovalent functionalization retains the chemical compatibility without distorting the π–π conjugation and the associated physicochemical properties of the individual dye molecules. Along with the expanded consumption of non-photosynthetically active solar radiation, an improved power conversion efficiency of greenhouse-integrated DSC is accordingly expected.

Molecular cosensitization is favorable for manipulating solar radiation through the judicious choice of cosensitizers having complementary absorption spectra.     

Role of peritoneal ultrasonography and ultrasound-guided fine needle aspiration cytology/biopsy of extravisceral masses in the diagnosis of ascites of undetermined origin

Background and study aimsAscites may be of undetermined origin despite comprehensive study. This study aimed to assess the accuracy and safety of conventional and interventional high-frequency peritoneal ultrasound in the diagnosis of patients with ascites of unclear origin.Patients and methodsA total of 62 patients were prospectively enrolled; they underwent conventional (3.5–5 MHz) and high-frequency (6–8 MHz) transabdominal peritoneal ultrasound to suggest the nature of ascites supplemented by fine needle aspiration cytology (FNAC) of ascites and/or core biopsy of the omentum or other extra-visceral masses for final histopathologic diagnosis. Laparoscopy or laparotomy was needed if biopsy was inconclusive.ResultsUltrasound-guided procedures were diagnostic in 55 (87.7%) patients. Thirty-six (58.1%) were benign, of whom 86% had tuberculous peritonitis, 26 (41.9%) were malignant, of whom 76.9% had peritoneal metastasis. High-frequency ultrasound was able to propose ultrasonographic criteria in a trial to diagnose the nature of ascites. Our proposed ultrasonographic criteria were based on the amount and texture of ascites in addition to the omental and mesenteric features. These were able to suggest the diagnosis with 80.7% sensitivity for malignant ascites and 75% specificity for benign ascites. Moreover, histopathological examination of tissues obtained by ultrasound-guided procedures increased the sensitivity to 88.5% and the specificity to 88.9% in diagnosing malignant and benign disease, respectively, with an overall diagnostic accuracy of 88.6%. These procedures were considered to be safe as only one major (haemoperitoneum) and two minor complications (temporary ascitic fistula) were reported.ConclusionHigh-frequency peritoneal ultrasound together with the minimally invasive ultrasound-guided FNAC/biopsy of extra-visceral lesions may be considered an effective and safe tool in the diagnosis of ascites of undetermined origin.     

Utero-cutaneous fistula following cesarean section: A case report

Utero-cutaneous fistula is a rare pathology. It mostly occurs consecutively to surgical intervention such as Cesarean section. Blood discharge from the cesarean scar during menstruation is a quasi-pathognomonic feature. Imaging modalities, particularly with the injection of contrast material through the cutaneous fistulous opening, confirm the diagnosis. The management is mainly surgical.We report the case of a utero-cutaneous fistula in a 27-year-old lady, with systemic lupus erythematosus. She presented seven months after her third cesarean section with pain and blood discharge from the cutaneous scar during menstruation for four months. A pelvic CT scan with the injection of the contrast material through the cutaneous fistulous opening confirmed the diagnosis of utero-cutaneous fistula. Surgical management was successful.     

Comparison of the Seventh and Eighth Edition of American Joint Committee on Cancer (AJCC) Staging for Selected and Nonselected Oropharyngeal Squamous Cell Carcinomas

ObjectivesThe eighth edition American Joint Committee on Cancer (AJCC) Staging incorporates significant changes to the seventh edition in the staging of oropharyngeal squamous cell carcinomas (OPSCC). An important change was the inclusion of OPSCC associated with the human papilloma virus (HPV). Our goal is to compare the performance of both staging systems for patients with HPV-selected and unselected clinical characteristics for OPSCC.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2016, we identified patients with likely HPV-associated OPSCC based on surrogate markers (white males aged <65 years old with squamous cell carcinomas of the tonsil and base of tongue), excluding those who underwent surgery. We re-classified these patients using seventh and eighth edition staging for HPV-selected OPSCC and compared the prediction performance of both staging editions for overall survival (OS) and disease-specific survival (DSS). We performed the same analysis for clinically unselected patients with OPSCC.ResultsOur analysis included 9554 patients with a median follow-up of 67 months. Comparing the eighth versus seventh edition for our HPV-selected cohort, clinical staging changed for 92.3% of patients and 10-year OS was 62.2%, 61.2%, 35.3%, and 15.5% for Stage I, II, III, and IV, versus 52.9%, 59.2%, 61.6%, 55.1%, 38.3%, and 15.5% for stage I, II, III, IVA, IVB, and IVC, respectively. A similar pattern was observed for 10-year DSS. The concordance statistics for our HPV-selected cohort were improved for both AJCC 7 (0.6260) and AJCC 8 (0.6846) compared with the unselected cohort, 0.5860 and 0.6457 for AJCC 7 and 8, respectively.ConclusionThe overall performance of discrimination improved from AJCC 7 to AJCC 8 for both clinically selected and unselected patients, but more notably for our HPV-selected cohort. Despite the lack of statistically significant differentiation between Stages I and II in AJCC 8 in either groups, markedly improved discrimination was observed between Stages I/II, III, and IV in the HPV-selected cohort.     

Elective neck dissection in T1/T2 oral squamous cell carcinoma with N0 neck: essential or not? A systematic review and meta-analysis

European Archives of Oto-Rhino-Laryngology - Oral squamous cell carcinoma (SCC) is characterized by a high risk of cervical lymph node metastasis with a high incidence of occult metastasis. A...     

Randomized Pilot Study of 20 Gy in 5 Fractions versus 27 Gy in 3 Fractions Radiotherapy for Treating Painful Bone Metastases: A Single Institution Experience

Purpose: Radiotherapy is a very effective tool in the treatment of painful bone metastases. The aim of this study was to compare the palliative effect of radiotherapy between the standard fractionation schedule 20 Gy over 5 fractions (20Gy/5fr) and the high biological dose schedule 27 Gy over 3 fractions (27Gy/3fr) which is frequently used in Stereotactic body radio-surgery (SBRT). Methods: Patients were randomized to receive (20Gy/5fr)or (27Gy/3fr). The primary aim of the study was pain relief using the numeric rating scale (NRS), after three months of radiation therapy. Secondary end points include pain relief immediately after finishing radiation therapy (within one week), and narcotic relief after three months of radiation therapy. Results: Twenty-two patients with painful bone metastases were included. 12 patients received (20Gy/5fr) and 10 patients received (27Gy/3fr). Male patients were predominant on both arms (81.8%) with a mean age of 58 years [ranging between 19-72 years]. For pain relief after three months of radiation therapy, partial pain relief was documented in 9 patients (75%) with (20Gy/5fr) and in 8 patients (80%) with (27Gy/3fr) with a p- value of 0.6. Additionally, narcotic relief after three months was equal for both groups. For immediate pain relief, partial pain relief was seen in one patient (8%) with (20Gy/5fr) versus seven patients (70%) with (27Gy/3fr) with a p value of 0.06. The increase in immediate pain relief in the 27Gy arm was numerically but not statistically significant. Conclusion: SBRT and standard fractionation radiation therapy had equal effectiveness for pain relief, when the assessment was done after three months of radiation therapy. Interestingly, SBRT had a better immediate pain relief.