The prognostic and predictive role of class III ß-Tubulin and hENT1 expression in patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: FOLFIRINOX and gemcitabine-nabpaclitaxel (GnP) are standard first-line treatment regimens for advanced pancreatic ductal adenocarcinoma (PDAC). However, currently, there is a lack of predictive biomarkers to aid in the treatment selection. We aimed to explore the prognostic and predictive value of class III ß-Tubulin (TUBB3) and human equilibrative nucleoside transporter 1 (hENT1) expression, which have previously been shown to be associated with taxane and gemcitabine resistance in advanced PDAC. METHODS: We conducted a retrospective analysis of 106 patients with advanced PDAC treated with GnP and/or FOLFIRINOX at our institution. TUBB3 and hENT1 immunohistochemical staining was performed on tumor specimens and subsequently evaluated based on the intensity and percentage of expression. RESULTS: In patients who received the GnP regimen, a high combined score (TUBB3low/hENT1high) was associated with a higher DCR and longer PFS compared to those with intermediate (TUBB3high/hENT1high or TUBB3low/hENT1low) and low score (TUBB3high/hENT1low). In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR:11.96; 95 % CI:2.61-54.82; p = 0.001) and longer PFS (HR:0.33; 95%CI:0.18-0.60; p < 0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving the FOLFIRINOX regimen. CONCLUSION: Our findings indicate that tumor TUBB3 and hENT1 expression may predict the efficacy of the GnP regimen, and low TUBB3 and high hENT1 expression (TUBB3low/hENT1high) are associated with a higher DCR and longer PFS in patients treated with GnP. Evaluating TUBB3 and hENT1 jointly can identify the patients most (as well as least) likely to benefit from GnP chemotherapy.

Can lactate be valuable in early diagnosis and prognosis of neonatal sepsis?

Background: Sepsis monitoring tissue perfusion is crucial for detecting circulatory failure early, implementing the right treatments, and assessing response. Insufficient oxygenation leads to a rise in lactate level and has been shown to be useful in predicting mortality and morbidity in newborns. There have not been many studies on how lactate measurement affects neonatal sepsis diagnosis and prognosis. Aim: The aim of our study was to determine the impact of lactate on early diagnosis and prognosis in neonatal sepsis. Materials and Methods: Eighty-seven newborns diagnosed with neonatal sepsis at a neonatal intensive care unit between January 2010 and July 2021 were included in the study. Venous blood gas, lactate, and C-reactive protein (CRP) levels and complete blood count on the first, second, and third day of hospitalization were noted. Lactate values were correlated with other variables to determine the impact of hyperlactatemia on morbidity and to determine factors affecting the length of stay. IBM SPSS Statistics version 22.0 for Windows was used to analyze the data (SPSS Inc., Chicago, IL, United States). Results: A strong negative correlation between lactate and oxygenation and perfusion indicators (HCO3, BE, PaO2) during the therapeutic process was observed. With treatment, the initial measured lactate value decreased, and a significant increase in CRP and oxygen saturation was observed, which was interpreted as the observation of an early lactate response to infection before a CRP response. The initial lactate level, as well as the change in lactate levels, was not, however, significantly correlated with the length of stay. Conclusion: Lactate can be used in the early diagnosis of neonatal sepsis and for determining prognosis.

The disappearance of respiratory syncytial virus and influenza viruses in children during the second year of the COVID-19 pandemic - are non-pharmaceutical interventions as effective as vaccines?

OBJECTIVE: Respiratory viral diseases are common in children. A viral diagnostic test is necessary, because COVID-19 shows signs and symptoms similar to those of common respiratory viruses. The article aims at analyzing the presence of respiratory viruses that were common before the pandemic in children who were tested for suspected COVID-19, and is also concerned with how common respiratory viruses were impacted by COVID-19 measures during the second year of pandemic. PATIENTS AND METHODS: Nasopharyngeal swabs were examined to detect the presence of respiratory viruses. The respiratory panel kit included SARS-CoV-2, influenza A and B, rhinovirus/enterovirus, parainfluenza 1, 2, 3 and 4, coronaviruses NL 63, 229E, OC43, and HKU1, human metapneumovirus A/B, human bocavirus, respiratory syncytial virus (RSV) A/B, human parechovirus, and adenovirus. Virus scans were compared during and after the restricted period. RESULTS: No virus was isolated from the 86 patients. SARS-CoV-2 was the most frequently observed virus, as expected, and rhinovirus was the second, and coronavirus OC43 was the third. Influenza viruses and RSV were not detected in the scans. CONCLUSIONS: Influenza and RSV viruses disappeared during the pandemic period and rhinovirus was the second most common virus after the CoVs during and after the restriction period. Non-pharmaceutical interventions should be established as a precaution to prevent infectious diseases even after the pandemic.

Clinical and laboratory predictors of long-COVID in children: a single center retrospective study.

OBJECTIVE: The majority of children experience a mild course of acute Coronavirus Disease 2019 (COVID-19). Only few studies have looked at long-term recovery from COVID-19 infection in children. The purpose of this study was to identify the predictors of long-COVID by performing a thorough analysis of the clinical, laboratory, and demographic characteristics of children with COVID-19. PATIENTS AND METHODS: Between August and October 2021, data were obtained retrospectively from the medical records of 251 children diagnosed with COVID-19 at a tertiary single-center hospital. The prognostic effects of admission-related factors were compared between patients who experienced long-lasting symptoms and those who did not. RESULTS: Long-COVID symptoms were noted in 12.4% of patients. Joint pain (7.6%), lumbago (4.8%), and headache (3.2%) were the most common symptoms. The mean onset of long-COVID symptoms was 1.35±0.49 months. The onset of long-COVID symptoms was 4 weeks after initial diagnosis in 64.5% of patients and 4-8 weeks later in 35.5% of the patients. The mean duration of long-COVID symptoms was 5.32±2.51 months. Children with long-COVID had higher leukocytes, neutrophils, monocytes, basophils, platelets, and D-dimer when compared with patients without long-COVID (p < 0.001). Leukocytes, neutrophils, monocytes, platelets, and D-dimer had the highest AUC in the ROC analysis (0.694, 0.658, 0.681, 0.667, and 0.612, respectively) and were statistically significant. CONCLUSIONS: Despite the majority of children with COVID-19 having mild or asymptomatic acute disease, the majority of long-COVID symptoms were associated with functional impairment between 1 and 9 months after the start of the infection. Increased leukocytes, monocytes, neutrophils, platelets, and D-dimer appear to be the most powerful laboratory predictors for long-COVID and monitoring these predictors may assist clinicians to identify and follow-up patients with higher risk for long-COVID.

PROPROTEIN CONVERTASE 1/3 DEFICIENCY WITH PELVIC EWING SARCOMA.

Proprotein convertase 1/3 (PC 1/3) deficiency is a rare, autosomal recessive disorder caused by mutations in the PCSK1 gene. The disease is characterized by early-onset chronic diarrhea/malabsorption, followed by severe obesity and hormonal deficiencies such as hypocortisolism, hypothyroidism, diabetes insipidus, hypogonadism, growth deficiency, and diabetes mellitus. Ewing's sarcoma is a rare tumor, usually of small dimensions of neuroectodermal origin that is difficult to distinguish pathologically from a primitive neuroectodermal tumor. A 22-year-old female patient with PC 1/3 deficiency was admitted to our clinic with recurrent urinary tract infections. Magnetic resonance imaging (MRI) revealed an 11x12 cm pelvic mass displacing the uterus. A core-needle biopsy was performed on the pelvic mass. As a result of the pathological evaluation, it was diagnosed with pelvic Ewing's sarcoma. The patient was started on the VAC-IE chemotherapy protocol. We report a case of pelvic Ewing's sarcoma in a patient with PC 1/3 deficiency. Further research is needed to assess malignancy risk in metabolic disorders including very rare disorders like PC 1/3 deficiency.

PILE: a candidate prognostic score in cancer patients treated with immunotherapy

Background Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. Methods A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. Results The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2–3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450–3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263–2.954, p = 0.002) compared to PILE low-risk group (PILE score 0–1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. Conclusion In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy. (AU)

PILE: a candidate prognostic score in cancer patients treated with immunotherapy.

BACKGROUND: Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. METHODS: A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. RESULTS: The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2-3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450-3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263-2.954, p = 0.002) compared to PILE low-risk group (PILE score 0-1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. CONCLUSION: In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy.

Clinical and pathological diagnosis and comparison of benign and malignant eyelid tumors.

PURPOSE: To assess and compare demographic and clinical features of benign and malignant eyelid tumors from 2011 to 2018 in a tertiary medical center. MATERIALS AND METHODS: The study was conducted retrospectively from medical records to compare demographic and clinical characteristics and recurrence of benign and malignant eyelid tumors after obtaining institutional review board approval. A total of 428 eyelid tumors with histopathologic diagnoses were studied. Premalignant lesions were not included. The lesions were classified into two groups according to malignancy: benign and malignant eyelid lesions. RESULTS: Among the 428 histopathologically confirmed eyelid lesions, 373 (87.1%) were benign and 55 (12.9%) were malignant. The patients with malignant eyelid tumors had a higher mean age at diagnosis than patients with benign eyelid tumors (P=0.012). The most common benign eyelid tumors were squamous papilloma (17.7%), xanthelasma (11.5%), and epidermal cysts (11.3%). The most common malignant eyelid tumors were basal cell carcinomas (65.5%), squamous cell carcinomas (14.5%), and sebaceous gland carcinomas (7.3%). There was no relative gender predominance between patients with benign and malignant eyelid tumors (P=0.287). Benign eyelid tumors were most commonly located on the right side and upper eyelid (P=0.027 and 0.036, respectively). Malignant tumors had a higher rate of recurrence (P=0.002). CONCLUSION: Differentiation between benign and malignant eyelid lesions is important, since it may lead to cosmetic complications and serious morbidity, particularly in patients with malignant eyelid tumors.

Case of metastatic kaposi sarcoma successfully treated with anti-PD-1 immunotherapy.

INTRODUCTION: Kaposi sarcoma (KS) is an angioproliferative malignancy associated with HHV-8. It is mostly observed in patients affected by HIV and/or chronic immunosuppression, while classic KS without underlying immunosuppression are relatively rare. Systemic chemotherapy is used for advanced diseases, although there is no consensus in treatment algorithms. With the demonstration of PD-1 expression in KS, immune-checkpoint-inhibitors (ICI) emerged as possible treatment options. Notwithstanding, the data of ICIs is limited to case reports/series. Herein, we present a case of advanced classic KS, which has been treated successfully with nivolumab. CASE REPORT: 82-year-old male patient was investigated for erythematous lesions on thigh. Punch biopsy lead to KS diagnosis. Abdominal CT showed lymphadenopathies in the inguinal region. After radiotherapy follow-up, patient had shown vertebral & gastric metastases. Because of the PSA elevation patient was diagnosed with prostatic adenocarcinoma. Metastases were investigated for origin. The lesions showed no uptake in Ga-68 PET-CT, therefore accepted as KS metastases. Patient rejected chemotherapy options and consented to immunotherapy trial.Management and outcome: Nivolumab was initiated 3 mg/kg bi-weekly with 12-dose protocol. After nivolumab patient wellbeing is improved and control endoscopy shown no metastases. With these findings patient has been assessed as complete response. DISCUSSION: ICI on KS is still a blurred option to be included in standard regimens; but progressive understanding of PD-1 expression and its role in disease progression may be a milestone for further treatment algorithms on KS. Besides good efficacy, tolerability of ICIs could be helpful patients with comorbidities precluding the use of chemotherapy.

Nivolumab for the salvage treatment of desperate germ cell tumor: A case report.

INTRODUCTION: Testicular germ cell tumors (GCT) are the most common tumor in young men. Their distinctive feature is the exceptional response to platin based combination chemotherapy.Since the prognosis is poor in relapsed and refractory patients, the immune checkpoint inhibitors are candidate agents in these patients although clinical trials are mostly lacking. Herein, we describe a patient with a refractory nonseminomatous GCT using nivolumab as a last resort therapy and provided long term response without any significant toxicity. CASE REPORT: A 41-year-old male presented with the complaint of flank pain eleven years ago. The patient underwent a retroperitoneal lymph node excision and pathology reported as the mixed germ cell tumor. There were no mass in the testicles and the patient was diagnosed with a primary retroperitoneal GCT. Since the disease has progressed under multiple lines of chemotherapy and autologous stem cell transplantation, treatment was started with nivolumab. MANAGEMENT AND OUTCOME: The patient started to treatment with nivolumab 3 mg/kg two weekly as a last resort treatment. The nivolumab was continued and the patient's response to this treatment is ongoing and has been stable for 13 months. DISCUSSION: There are limited treatment options in platinum-refractory germ cell tumors. Recently, immune checkpoint inhibitors tried in this setting with some success in especially non-seminomatous GCTs. We see a good response and prolonged benefit with the use of nivolumab in our patient. Further research including prospective studies on the use of immune checkpoint inhibitors in platinum-resistant testicular cancer can further delineate the role of immunotherapy.

Enhancement of nutrient removal performance of activated sludge with a novel hybrid biofilm process.

The aim of this study was to investigate the efficacy of a hybrid biofilm pilot-scale treatment plant, designed with a novel configuration by the integration of a fixed-film system, to improve nitrogen removal. The pilot-scale system was established at a wastewater treatment plant in Istanbul and operated based on stream separation following a process consisting of Bio-P and primary sedimentation units in which carbonaceous compounds were entrapped/incorporated in settled biomass. The ammonia-rich supernatant was directed to a moving bed biofilm (MBBR) nitrification tank to obtain an efficient nitrification with the reduced organic loading after the primary sedimentation. The conventional activated sludge process, for which the net specific growth rate ([Formula: see text]) was measured to be 0.26 day-1 at 15 °C, exhibited a low nitrification capacity. However, the pilot-scale hybrid biofilm system secured nitrification performance up to 1.8 gN/m2/day ammonia loading, providing a competitive advantage over the conventional single sludge systems. The proposed hybrid configuration enables removal efficiencies of 80% and 85% for total nitrogen and phosphorus. It was possible to entrap organic matter by mixing 30% of return activated sludge (RAS) with raw wastewater. Simulation-based design study showed that the use of the hybrid biofilm system reduces the environmental footprint and aeration requirement of the nutrient removal by about 50% and 19%, respectively. Economic analyses highlighting the benefit of hybrid biofilm over conventional BNR system are illustrated.

Histomorphometric changes in the placenta and umbilical cord during complications of pregnancy.

Pregnancy complications may cause morphological changes and circulation defects in the placenta, which may lead to morbidity and mortality in fetuses and newborns. We investigated structural changes in the placenta and umbilical cord under various abnormal maternal conditions. Placenta and umbilical cord specimens were obtained from pregnant women during labor at 37 - 42 weeks gestation. Volumetric measurements were made for each placenta and umbilical cord using the Cavalieri method. Significant differences were observed for volumetric densities of total villi, syncytial knots, intervillous vessels and perivillous fibrin deposition. We observed particular increases in the volumetric parameters of the pre-eclampsia group compared to the other groups. The tunica media of the umbilical arteries was increased significantly with intrahepatic cholestasis.

Multicenter study of pars plana vitrectomy for optic disc pit maculopathy: MACPIT study.

PurposeTo evaluate surgical intervention with pars plana vitrectomy (PPV) for correction of optic disc pit maculopathy (ODP-M).Patients and methodsRetrospective chart review from 13 centres of 51 eyes of 50 patients with ODP-M who underwent PPV between 2002-2014. Anatomic and final best-corrected visual acuity (BCVA) outcomes were evaluated for all cases with different adjuvant techniques.ResultsThere were 23 males and 27 females with median age 25.5 (6-68) years. Preoperative median foveal thickness was 694.5 (331-1384) µm and improved to 252.5 (153-1405) µm. Median BCVA improved from 20/200 (20/20000 to 20/40) to 20/40 (20/2000 to 20/20) with 20/40 or better in 31 eyes. Complete retinal reattachment was achieved in 44 eyes (86.3%) at 7.1 (5.9) months. The good surgical outcomes were achieved in different adjuvant groups. Median follow-up was 24 (6 to 120) months.ConclusionsThese results confirm the long-term effectiveness of PPV for ODP-M. Prospective studies are needed to determine the effectiveness of any adjuvant technique in improving the success of PPV for ODP-M.

Kinetic evaluation of nitrification performance in an immobilized cell membrane bioreactor.

High rate membrane bioreactor (MBR) systems operated at extremely low sludge ages (superfast membrane bioreactors (SFMBRs)) are inefficient to achieve nitrogen removal, due to insufficient retention time for nitrifiers. Moreover, frequent chemical cleaning is required due to high biomass flux. This study aims to satisfy the nitrification in SFMBRs by using sponge as carriers, leading to the extension of the residence time of microorganisms. In order to test the limits of nitrification, bioreactor was run under 52, 5 and 2 days of carrier residence time (CRT), with a hydraulic retention time of 6 h. Different degrees of nitrification were obtained for different CRTs. Sponge immobilized SFMBR operation with short CRT resulted in partial nitrification indicating selective dominancy of ammonia oxidizers. At higher CRT, simultaneous nitrification-denitrification was achieved when accompanying with oxygen limitation. Process kinetics was determined through evaluation of the results by a modeling study. Nitrifier partition in the reactor was also identified by model calibration.

Is parturition-timing machinery related to the number of inhibitor CD94/NKG2A positive uterine natural killer cells?

PURPOSE: Prematurity is the most common cause of infant mortality and morbidity. To prevent this, the timing of parturition and its mechanisms should be understood. It is likely that inhibitor CD94/NKG2A positive decidual natural killer cells (uNK) provide for the continuation of pregnancy. Here, we aimed to evaluate whether CD94/NKG2A positive uNK cells are highest in elective cesarian section (C/S) (suggesting ongoing gestation), moderate in normal full-term birth, and lowest in pre-eclamptic parturition. METHODS: Of 48 pregnant women, 21 C/S, 16 normal, and 11 pre-eclamptic deliveries were included in this study. Five placentas in each group were assigned randomly. After staining, the volumetric analysis of the placental villi and villous blood vessels was performed via the Cavalieri principle. The CD94/NKG2A positive uNK cells were counted using the physical disector method. RESULTS: The gestation periods and birth weights of the pre-eclamptic deliveries were lower than those of the other two groups. Additionally, the villi and villous vascular volumes were lowest in the pre-eclamptic placentas. As proposed in our hypothesis, the inhibitor CD94/NKG2A positive uNK cells were the highest in the C/S, moderate in the normal, and lowest in the pre-eclamptic placentas. CONCLUSIONS: These data suggest that CD94/NKG2A positive uNK cells are related with the continuation of pregnancy, and that our human model could be used to search for parturition-timing machinery. We believe that CD94/NKG2A positive uNK cells are also related to the timing of birth.

Stereological and histopathological evaluation of ovary and uterine horns of female rats prenatally exposed to diclofenac sodium.

In this study, we investigated the morphometric and histological alterations of the ovary and uterine horns in 4-week-old rats that were prenatally exposed to diclofenac sodium (DS). For this purpose, pregnant rats were divided into two groups: the control and drug-treated groups. Beginning from the 5th day after mating through the 15th day of pregnancy, DS (1 mg/kg daily) was intraperitoneally injected in the treated group. No injection was given to the rats in the control group. After spontaneous delivery, male offspring were obtained. At the end of the 4th week, ovary and uterine horn samples were removed. Following dissection and routine histological preparation, histopathological and stereological investigations were carried out. Our results indicate that DS application leads to a decrease in the mean volume fraction of the uterine horn. Moreover, there was an increased volume fraction in some structures of the ovary; like the cortex, medulla and zona granulosa. There was no difference found between the two groups in terms of the mean volume of the antrum and the Graafian follicle fraction. Finally, in light of our findings, we may suggest that DS may lead to adverse effects in rats that are prenatally subjected to this drug.