Surgical Excision of Unusual Sacked Neck and Mediastinum Abscess of Odontogenic Origin.

The most common cause of neck infections is odontogenic abscesses that can often be life-threatening and require a surgical drain associated with antibiotic therapy. We present a case of the surgical management of an odontogenic sack-shaped and walled abscess arising from elements 3.6, 3.7 and 3.8 that reached the laterocervical spaces and anterior mediastinum in a 28-year-old healthy woman. Typical signs and symptoms of cervical complications of dental origin are fever, a neck mass, lymphadenopathy, trismus and odynophagia. The gold standard treatment in these situations is a multidisciplinary approach involving an oral surgeon, ENT specialist and thoracic surgeon to drain the infected material. To the best of our knowledge, this is the first described case report of a dental abscess enclosed in a sack in the deep space of the neck and in the anterior space of the mediastinum.

Fetal and post-natal growth in infants of mothers with multiple sclerosis: A case-control stud.

BACKGROUND: Multiple sclerosis does not seem to adversely affect fetal and neonatal outcomes, although some studies reported a possible reduction in mean birth weight and length, and a higher incidence of preterm delivery, mainly in relation to the exposure to disease-modifying drugs (DMDs) during pregnancy. Few data are available on intrauterine fetal growth and postnatal somatic development of newborns from mothers with multiple sclerosis compared to those from healthy women. For these reasons, we decided to investigate fetal growth, neonatal anthropometric parameters, and postnatal somatic development up to 12 months of life in offsprings from MS mothers. METHODS: This retrospective cohort study included 211 women with multiple sclerosis, and 384 healthy women paired for maternal age and parity as controls. Fetal biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) measured during the third trimester of pregnancy (30-34 weeks' gestation) were retrieved from the computerized database of the Department (EcoPlus*) where the results of ultrasound exams performed in the hospital are stored. Newborn measurements (weight, length and head circumference) at birth were obtained from the hospital's computerized obstetric and neonatal database (Trackare* and Remote* data base); measurements at 6 and 12 months of life were obtained from the regional database (ECWMED*) of family pediatricians of our region. RESULTS: No differences between the two groups were observed for all the fetal parameters considered, expressed as centiles of growth according to gestational age (biparietal diameter: p = 0.40; head circumference: p = 0.40; abdominal circumference: p = 0.32; femur length: p = 0.32). No differences in gestational age at delivery, birthweight, and in the incidence of low birthweight and small for gestational age newborns were observed between the two groups. In the multiple sclerosis group a significantly higher incidence of caesarean section (p = 0.01) and late preterm delivery (at less than 37 weeks'gestation, p = 0.001) were registered. The trends of postnatal growth in weight (F = 0.53; p-value = 0.590) and length (F = 0.44; p-value = 0.645) were superimposable between the two groups. The trends of growth for head circumference showed a slightly, not significantly greater head circumference of infants from mothers with multiple sclerosis at 6 months of life, but the values at twelve months of life in the two groups were similar (F = 0.85; p-value = 0.427) . Moreover, the trends of postnatal increase of weight (F = 1.016; p-value = 0.331), length (F = 2.001; p-value = 0.146) and head circumference (F = 1.591; p-value = 0.212) of newborns/infants (from birth to twelve months of life) born to mothers with multiple sclerosis who breastfed, mothers who did not, and in the control group were similar. CONCLUSION: Multiple sclerosis in pregnancy does not seem to affect fetal growth and postnatal development during the first year of the offspring life. We think that these results represent an important and reassuring information to provide the patients with during preconception counseling.

Influence of Implant Scanbody Wear on the Accuracy of Digital Impression for Complete-Arch: A Randomized In Vitro Trial.

The aim of this study was to evaluate the influence of implant scanbody (ISB) wear on the accuracy of digital impression for complete-arch. A polymethylmethacrylate (PMMA) edentulous mandibular model with four internal hexagonal interlocking conical connections was scanned with an extraoral optical scanner to achieve a reference file. Four cylindrical polyetheretherketone (PEEK) ISBs were scanned 30 times with IOS, and the test files were aligned to the reference file with a best-fit algorithm. For each analog linear (ΔX, ΔY and ΔZ-axis) and angular deviations (ΔANGLE) were assessed. Euclidean distance (ΔEUC) was calculated from the linear deviation, reporting a mean of 82 µm (SD 61) ranging from 8 to 347 µm. ΔANGLE error mean was 0.33° (SD 0.20), ranging from 0.02 to 0.92°. From a multivariate analysis, when ΔEUC was considered as a response variable, a significant influence of ISB wear by scan number in interaction to position for implant 3.6 was identified (p < 0.0001); when ΔANGLE was considered as a response variable, a significant effect of position 3.6 was recorded ((p < 0.0001). The obtained results showed that the ISB wear negatively influenced the accuracy of IOS, suggesting that ISB base wear could be detrimental for the seating of ISBs on angulated implants.

Pembrolizumab for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: Analysis of Prognostic Factors of Outcomes.

BACKGROUND: In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe. OBJECTIVE: To evaluate retrospectively the safety and efficacy of this drug and to investigate potential prognostic factors in daily clinical practice. METHODS: From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study. Gender, Age (> or <70 years), ECOG-PS (0-1 or 2), histology (squamous or nonsquamous), presence of brain, bone and liver metastases at baseline, PD-L1 score (>90% or <90%), smoking status (never or former or current) were applied to the stratified log-rank. Cox's proportional hazards model was used for multivariate analysis. RESULTS: At a median follow-up of 15.2 months, median progression-free and overall survival (mPFS and mOS) were 9.2 months (95% C.I., 4.8-13.5) and 15.9 months (95% C.I., not yet evaluable), respectively. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 had mPFS of 2.8 months (95% C.I., 2.1-3.4) and mOS of 3.9 months (95% C.I., 2.5-5.3). Patients with liver metastases at diagnosis had an mPFS of 3.2 months (95% C.I., 0.6-5.8) and an mOS of 6.0 months (95% C.I., 3.7-8.4). At multivariate analysis for OS gender, ECOG-PS 2, and presence of liver metastases were independent prognostic factors. CONCLUSION: Patients with ECOG-PS 2 derived little benefit from the use of first-line pembrolizumab. In patients with liver metastases, the association of pembrolizumab with platinum-based chemotherapy could be a better option than pembrolizumab alone.

Adherence, persistence and efficacy of dasatinib and nilotinib in the treatment of patients resistant or intolerant to imatinib with chronic myeloid leukemia in chronic phase: an Italian multicenter study over two years in real life.

BACKGROUND: The use of dasatinib and nilotinib in the treatment of patients with chronic myeloid leukemia represents a valid therapeutic option for patients resistant or intolerant to imatinib. In this multicentre study, adherence, persistence and efficacy in real life over two years of treatment were evaluated. MATERIALS AND METHODS: Adherence to treatment was calculated as the ratio between the dose received and the prescribed dose. The dose received was calculated using pharmacy refill data. The persistence with treatment was calculated as the difference between the end and the beginning of the treatment. Efficacy was assigned as Progression-Free Survival (PFS) and Events-Free Survival (EFS) and represented through the Kaplan-Meier curve. RESULTS: The number of patients analysed was 117, 70 treated with dasatinib and 47 with nilotinib. Adherence to treatment for dasatinib and nilotinib at two years was 0.91 and 0.82 respectively. Persistence at two years was 77% while the PFS was 92% for both drugs in the study. CONCLUSION: Adherence to the treatment calculated over two years showed a superiority of dasatinib over nilotinib. Nevertheless, the efficacy in terms of PFS and EFS is superimposable between the two drugs in the study.

Minimally Invasive Intraoral Approach to Submandibular Lodge.

The purpose of this study is to describe the Minimally Invasive Intraoral Approach (MIIA) performed on selected cases of abscesses and neck phlegmons of odontogenic origin when the infection has not spread beyond the inferior mandibular margin. This technique allows us to avoid cervicotomy by a direct approach to the abscess, draining it through the oral cavity. If the limits have already been crossed, then cervicotomy is necessary. The aim of the study is to show the surgical outcomes that we have achieved during a time span of two years, and to show the effectiveness of the MIIA and its results. We selected 66 patients with abscesses and neck phlegmons, from January 2018 to June 2020. Among these cases, five patients were excluded as it was not possible to recover medical records from database. The MIIA technique has been performed on 16 patients (26.2%) when a successful dental extraction and drainage of the submandibular lodge were accomplished. The patients who underwent the MIIA surgery have all perfectly healed and did not suffer from relapses during the follow-up. The results show the achievement of excellent healing, underlining the lower impact required by MIIA when compared to a more traditional approach through cervicotomy.

Surgical and orthodontic rapid palatal expansion in adults using a modified palatal partial osteotomy technique (ppot): Technique description and clinical experience.

Transversal hypoplasia of the upper maxilla is a frequent condition between malocclusions. The rapid maxillary expansion (RME) is an already consolidated technique for these types of defects. This case report analyzes the outcome of a novel surgical technique that we named TOPP (Partial Palatal osteotomy technique) aiming to provide scientifically proven data over the percentage of relapse and the long-term stability of this type of surgical assisted palatal expansion. A 24 year old male patient with a hyperdivergent class III, presenting the absence of 1.1 due to a teenage trauma and a transversal contraction of the upper arch was selected for the surgery. The mucoperiosteal flap was performed at a palatal level with a paramarginal arch shape (from region 1.4 to 2.4) due to preserve the nasal-incisal vascular bundle and the mucoperiosteum was detached from the floor of the nose. A horizontal osteotomy was performed at 4-5 mm above the roots apexes; a sagittal osteotomy in a posterior direction was done at the level of the midline to divide the mesiopalatine suture and separate the maxilla in two halves. The only bony attachment that remained was represented by the perpendicular lamina of the palatal bone. The TOPP technique showed that it is possible to have a better control of both the intercanine and intermolar expansion, that is more difficult in the case of a conventional SARME. Other goals were a greater view and access to the site and the reduction of the risk of damaging the palatine fibromucosa. The incision of the archform paramarginal flap improves certainly the conditions of the palatal fibromucosa in the post operative and allows the reduction of the soft tissues' elastic return. Key words:Rapid maxillary expansion, orthognatic surgery, maxillary osteotomy.

Chronic maxillary sinusitis of dental origin and oroantral fistula: The results of combined surgical approach in an Italian university hospital.

Unilateral chronic maxillary sinusitis is a possible complication of odontogenic disease or dental treatment and is mainly due to the development of an oroantral fistula (OAF). The management of chronic maxillary sinusitis of dental origin (CMSDO) requires a combined treatment via endoscopic sinus surgery (ESS) and intraoral surgical treatment of the odontogenic source. The aim of this study is to present the results of our university hospital unit in the treatment and follow-up of a case series of 34 patients treated with a combined surgical approach for CMSDO due to OAF. All patients were treated with ESS combined with an intraoral approach. No intraoperative or immediate postoperative complications were observed; nasal synechia was found in 3 patients (8.82%). The overall success rate after the primary intervention was 94.12%; recurrence was observed in 2 cases (5.88%), both were suffering from diabetes mellitus and were tobacco smokers. Our results confirm that simultaneous surgery with a combination of an intraoral and endoscopic approach can be considered the best strategy for the long-term restoration of normal sinonasal homeostasis in selected patients with chronic odontogenic sinusitis and OAF, guaranteeing an effective treatment with minimal complications in the short and long term.

Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.

Safety and antitumor efficacy of (153)Sm-EDTMP and docetaxel administered sequentially to patients with metastatic castration-resistant prostate cancer.

BACKGROUND: Bone metastases are responsible for most of the morbidity associated with metastatic castration-resistant prostate cancer (mCRPC). Bone-seeking radiopharmaceuticals have been approved for palliation of painful skeletal metastases, but their clinical use is limited by concerns of toxicities both when administered alone and especially when combined with chemotherapy agents. OBJECTIVE: We investigated whether docetaxel administered to mCRPC patients after treatment with samarium-153-labeled ethylene-diamine-tetra-methylene-phosphonic acid (Sm-EDTMP) has increased toxicity and/or reduced antitumor efficacy. MATERIALS AND METHODS: Thirty mCRPC patients with skeletal metastases were enrolled. Patients received standard therapy with docetaxel (75 mg/m intravenously every 21 days for at least six cycles) on average 6 weeks after Sm-EDTMP (37 MBq/kg). Patients were monitored for the presence of toxicities, and antitumor efficacy was assessed by changes in serum prostate-specific antigen levels. Besides standard descriptive statistical analysis, progression-free survival and overall survival were defined using the Kaplan-Meier method. RESULTS: Over 80% of the patients showed favorable biochemical responses. Median time to progression was 9.1 months (mean 9.8, 95% confidence interval 7.8-9.9), and median overall survival was 19.9 months (mean 24.5, 95% confidence interval 16.9-22.8); five patients were still alive over 5 years after enrollment. No additional hematological toxicities were observed when docetaxel was administered after Sm-EDTMP other than those expected when administering the agent alone. CONCLUSION: Prior administration of Sm-EDTMP does not cause additional toxicities for subsequent treatment with docetaxel and does not reduce the antitumor efficacy of the latter. This work justifies further investigations on the possible synergistic effects of combined strategies with the two agents.

Left-sided IVC in left renal cell carcinoma.

AIM: Congenital anomalies of the inferior vena cava (IVC) are very rare and extremely diverse, reflecting the complexity of the embryological development of these structures. The variants must be differentiated from pathology, particularly lymphadenopathy, on imaging studies as their presence can affect surgical and interventional procedures in retroperitoneum. We describe two patients with renal cell carcinoma of left kidney and left IVC. CASE REPORT: First patient was taken up for left radical nephroureterectomy. During surgery the existence of a transposed left IVC was demonstrated. The second case is a fifty-four-year-old man; abdomen and pelvic CT-scan with coronal maximum intensity projection reconstruction showed a 7 cm heterogeneously enhancing neoformation involving the left kidney with intraparenchymal hematoma and a transposed left IVC. CONCLUSIONS: Preoperative detection of congenital IVC anomalies can prevent morbidity. Once diagnosed, appropriate care must be taken during the operation to expose and define the anatomic anomaly and protect it from injury.

5-fluorouracil pharmacokinetics predicts disease-free survival in patients administered adjuvant chemotherapy for colorectal cancer.

PURPOSE: To evaluate 5-fluorouracil (5-FU) and 5-fluoro-5,6-dihydrouracil (5-FDHU) pharmacokinetics and disease-free survival (DFS) in colorectal cancer patients given 5-FU-based adjuvant chemotherapy within a nonrandomized, retrospective, pharmacokinetic study. EXPERIMENTAL DESIGN: One hundred fifteen patients including 72 men (median age, 63 years; range, 36-79 years) and 43 women (median age, 60 years; range, 36-73 years) received 6 cycles of l-leucovorin 100 mg/m(2)/day and 5-FU 370 mg/m(2)/day i.v. boluses (5 days every 4 weeks). Individual plasma concentrations of 5-FU and 5-FDHU were determined on day 1 of the first cycle with a validated high performance liquid chromatography method, and the main pharmacokinetic variables were determined. Follow-up of all patients was extended up to 5 years after the end of adjuvant chemotherapy, and DFS was recorded. Univariate and multivariate analyses were conducted to evaluate any correlation among 5-FU pharmacokinetics, clinical and pathologic variables, and DFS. RESULTS: The area under the time/concentration curve (AUC) of 5-FU was significantly lower in 58 subjects who recurred (7.5 +/- 2.9 h x mg/L) with respect to other patients (9.3 +/- 4.1 h x mg/L). Furthermore, AUC values lower than 8.4 h x mg/L together with lymph node involvement and the interruption of treatment or reduction of doses were identified as risk factors at univariate analysis. The completion of 6 cycles of adjuvant treatment without dosage modifications was the only independent risk factor at multivariate analysis, despite a trend toward significance for 5-FU AUC values (cutoff value, 8.4 hxmg/L) was observed (P = 0.06). CONCLUSIONS: Pharmacokinetics of 5-FU should be regarded as an important factor for predicting disease recurrence in colorectal cancers.

Implementation of a congenital hypothyroidism newborn screening procedure with mutation detection on genomic DNA extracted from blood spots: the experience of the Italian northeastern reference center.

After a couple of decades from the institution of nationwide congenital hypothyroidism (CH) newborn screening program, the first generation properly treated is now displaying normal reproductive rate and the causative molecular defects are spreading from one generation to the next. In the present study we propose a method of detection of mutations in the thyrotropin receptor (TSHR) and in the paired box 8 (PAX8) genes that have been proved to be responsible for some forms of CH. The method, carried out by means of denaturing high-performance liquid chromatography (DHPLC) followed by direct sequencing, takes advantage of the CH newborn screening procedure, because genomic DNA for the analysis is extracted from the same blood spot collected for recall confirmation. Among 16 hypothyroid newborns with thyroid hypoplasia born between January 1999 and April 2005 in northeastern Italy, three heterozygous causative mutations in the TSHR gene were evidenced, whereas the analysis of the PAX8 gene revealed an unknown heterozygous substitution that could interfere with the start of transcription.

Analysis of B- and T-cell clonality and HLA class II alleles in patients with idiopathic thrombocytopenic purpura: correlation with Helicobacter pylori infection and response to eradication treatment.

Many authors have recently found a positive correlation between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP), the most common autoimmune hematological disorder. In order to clarify the pathogenic mechanism of H. pylori-associated ITP, we have investigated 52 consecutive ITP adult patients for Helicobacter pylori infection, B- and T-cell clonality and HLA class II alleles. Thirty-four ITP patients (65.4%) were infected by H. pylori and bacterium eradication was accompanied by a long-term platelet response in 17 (53.1%) of them. A B-cell clonality was found in three patients (5.8%, two patients H. pylori-negative and one patient H. pylori-positive). The ITP patients with H. pylori infection showed a HLA-DRB1*11, *14 and -DQB1*03 frequencies significantly higher and a -DRB1*03 frequency significantly lower than in H. pylori-negative patients. Moreover, an HLA-DQB1*03 pattern was associated with a higher probability of platelet response to eradication treatment. If our study documents the efficacy of eradication treatment in H. pylori-infected ITP patients, it may also help to identify different subgroups of ITP patients with probably different pathogeneses of thrombocytopenia and, finally, different responses to eradication treatment.

Efficacy and safety of phlebotomy to reduce transfusional iron overload in adult, long-term survivors of acute leukemia.

BACKGROUND: Transfusional iron overload is a frequent finding in long-term survivors of acute leukemia (AL). Only a few studies have reported the results of iron depletion therapy in this category of patients. STUDY DESIGN AND METHODS: Between January 1996 and July 2003, 26 consecutive adult patients who achieved complete remission of AL and developed transfusional iron overload underwent a weekly phlebotomy program at our transfusion center. Serum ferritin levels and transferrin saturation were monitored during the iron depletion therapy and the follow-up period. These AL patients were also checked for the presence of 12 hereditary hemochromatosis (HH) gene mutations. RESULTS: After a mean follow-up of 57.8 months, therapeutic phlebotomy (mean number of units collected, 36.6) was effective in reducing mean ferritin concentration and transferrin saturation from 1726.9 to 93.0 mg per L and from 54.7 to 23.3 percent, respectively. The presence of a HH gene mutation did not influence initial iron status or response to treatment. The phlebotomy program was well tolerated and no adverse events were recorded during or after collection. In three cases the time between phlebotomies was increased because of patient's poor compliance or low Hb levels. CONCLUSION: Our study shows that phlebotomies are a safe and effective method for reducing iron over-load in multiply transfused long-term AL survivors with secondary hemochromatosis.

Analysis of hemochromatosis gene mutations in 52 consecutive patients with polycythemia vera.

A literature review reports increased erythrocyte indices [hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin (MCH), MCH concentration] in subjects with hereditary hemochromatosis (HH). We, therefore, screened 52 consecutive patients with polycythemia vera for 12 HH gene mutations, comparing iron status and red cell parameters between patients positive or negative for HH gene mutations. Our results support the evidence that there is no association between these two conditions.