Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

Influence of COVID-19 Pandemic on Colorectal Cancer Presentation, Management and Outcome during the COVID-19 Pandemic.

The aim of the study was to investigate whether the COVID-19 pandemic and related measures had an influence on colorectal cancer (CRC) presentation, management, and outcomes; it was a retrospective monocentric study. CRC patients undergoing surgery during the COVID-19 pandemic (1 March 2020-28 February 2022) (group B) were compared with patients operated on in the previous two years (1 March 2018-29 February 2020) in the same unit (group A). The primary outcome was to investigate whether there were differences in concern regarding the stage at presentation, as a whole and after dividing groups based on cancer location (right colon cancer, left colon cancer, rectal cancer). Secondary outcomes included differences in the number of patients admitted from emergency departments and emergency surgeries between periods, and differences in the postoperative outcomes. A subanalysis within the pandemic group was conducted on the same outcomes, dividing the aforementioned group based on pandemic trends. Two hundred and eighty (280) were operated on during the study period: 147 in group A and 133 in group B. Stage at presentation was similar between groups; however, the subgroups analysis showed that in the pandemic group, the number of early-stage left colon cancer occurrences almost halves, yet not significantly. Emergency department referral was more common in group B (p-value: 0.003); in group B, they also had longer operations and there was a more frequent use of ostomy. No differences in the number of postoperative complications nor in the postoperative outcomes were found. Patients with CRC were more frequently referred through the emergency department during the COVID-19 pandemic and left-sided cancers appear to be generally diagnosed at a more advanced stage. Postoperative outcomes showed that high specialized colorectal units can deliver standard high-level treatment under high-pressure external conditions.

Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer's disease.

BACKGROUND: The complex pathophysiology of Alzheimer's disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit. METHODS: In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse- model. RESULTS: We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3-CA1 synapse, both basal synaptic transmission and long-term potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron-glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH-/- animals. CONCLUSION: In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer's disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the disease.

Acute appendicitis in elderly during Covid-19 pandemic.

PURPOSE: During the past months, the Italian Government has reduced the restrictions and access to hospitals. Since then, up to 40% of non-traumatic abdominal emergencies have had unusual delayed treatment. Given the rapidly evolving situation and the absence of evidence to support recommendations during the pandemic, it is useful to assess how the current situation is influencing the management of elderly with acute appendicitis. METHODS: Between February 2020 and December 2020, all patients older than 68 years old undergone appendectomy were included. Surgical approach, hospital stay, post-operative complications, radiology reports, and histologic examination were included in the retrospective analysis and compared with a same sample of the same period before the pandemic. RESULTS: Twenty-seven patients underwent appendectomy for acute appendicitis during the pandemic and 34 patients in the pre-outbreak period. Laparoscopic approach was completed in 51.8% of the cases, while conversion to laparotomy in 22.3% of patients and open procedure in the 25.9%, before the pandemic 73.6%, 14.7%, and 11.7%, respectively. During the pandemic, complicated appendicitis occurred in 59.3% of the cases (26.5% before the outbreak). One patient was treated for a pelvic abscess, while no minor complications were detected. No mortality rate was reported, with a mean hospital stay of 5.64 days during the outbreak and 4.21 days before the pandemic. CONCLUSION: Our data highlighted a partial delay in diagnosis in the elderly group, and an increase in complicated appendicitis also demonstrated by the need for conversion to laparotomy.

Description of the methodology for dosimetric quantification in treatments with 177Lu-DOTATATE. / Descripción de la metodología para la cuantificación dosimétrica en tratamientos con 177Lu-DOTATATE.

Implementation of dosimetry calculations in the daily practice of Nuclear Medicine Departments is, at this time, a controversial issue, partly due to the lack of a standardized methodology that is accepted by all interested parties (patients, nuclear medicine physicians and medical physicists). However, since the publication of RD 601/2019 there is a legal obligation to implement it, despite the fact that it is a complex and high resource consumption procedure. The aim of this article is to review the theoretical bases of in vivo dosimetry in treatments with 177Lu-DOTATATE. The exposed methodology is the one proposed by the MIRD Committee (Medical Internal Radiation Dose) of the SNMMI (Society of Nuclear Medicine & Molecular Imaging). According to this method, the absorbed dose is obtained as the product of 2factors: the time-integrated activity of the radiopharmaceutical present in a source region and a geometrical factor S. This approach, which a priori seems simple, in practice requires several SPECT/CT acquisitions, several measurements of the whole body activity and taking several blood samples, as well as hours of image processing and computation. The systematic implementation of these calculations, in all the patients we treat, will allow us to obtain homogeneous data to correlate the absorbed doses in the lesions with the biological effect of the treatment. The final purpose of the dosimetry calculations is to be able to maximize the therapeutic effect in the lesions, controlling the radiotoxicity in the organs at risk.

Sclerotherapy with 3% polidocanol foam for third- and fourth-degree hemorrhoids as "bridge treatment" during the COVID-19 pandemic in Italy.

PURPOSE: In Italy, colorectal surgery has been strongly affected with the vast majority (90%) of operations treating benign diseases, with an estimated overall 12-week cancellation rate of 72%. Little is known on how to best manage patients with benign diseases and the consequences this interruption of care will have in post-pandemic times. Proctologic diseases have social, psychological, and healthcare repercussions for their high incidence and great impact on the quality of life. METHODS: We decided to treated 10 urgent cases affected from III- and IV-degree hemorrhoids with 3% polidocanol foam in attempt to reduce hemorrhoidal symptoms while waiting for surgery so called "bridge treatment". RESULTS: During the follow-up no complications were occurred, and all patients had resolution of bleeding and pruritus with a mean VAS of 1 (range, 0-1). CONCLUSIONS: This treatment could reduce the bleeding that is the main symptom from which patients suffer and for which they underwent proctological evaluation and surgery. According to our preliminary experience in the impossibility of accessing the surgery during the COVID-19 pandemic, ST could be considered as the treatment of choice in those patients who are suffering from grade III- and IV-degree hemorrhoids while waiting for surgery.

Transperineal rectocele repair with biomesh: updating of a tertiary refer center prospective study.

PURPOSE: Symptomatic rectocele results in obstructed defecation and constipation. Surgical repair may provide symptomatic relief. A variety of surgical procedures have been used in the rectocele repair to enhance anatomical and functional results and to improve long-term outcomes. METHODS: In this prospective study, we treated 25 selected women suffering from simple symptomatic rectocele with transperineal repair using porcine dermal acellular collagen matrix Biomesh (Permacol®). Watson score and SF-36 questionnaire were used to evaluate postoperative outcomes and quality of life. RESULTS: Follow-up ranged from 12 to 24 months, the mean total Watson score was significantly lower than the preoperative score (P < 0.001), and every patient has improved functional outcomes. There were no major intraoperative or postoperative complications. Two cases of urinary infection and 4 patients delayed wound healing were reported. Those patients who were sexually active prior to surgery have not experienced problems with sexual function or dyspareunia. CONCLUSIONS: Despite lack of comparative study in literature, rectocele repair with Permacol® by the transperineal approach seems an effective and safe procedure that avoids some of the complications associated with synthetic mesh use.

Role of SPECT-CT in breast cancer sentinel node biopsy when internal mammary chain drainage is observed.

INTRODUCTION: SPECT-CT in the detection of the sentinel lymph node (SLN) of breast cancer offers known advantages over conventional planar lymphoscintigraphy. Sometimes, it shows atypical findings like mediastinal lymphatic drainage. We have evaluated these atypical findings showed by SPECT-CT performed in patients with migration to the internal mammary chain (IMC) and their roles in the management of the patients. MATERIALS AND METHODS: We reviewed the 56 lymphoscintigraphies (planar and SPECT-CT) of 56 women (average age: 55 years) diagnosed with breast cancer with IMC migration observed in the planar images. We compared the two techniques, obtaining the number of depicted nodes, atypical locations, their exact anatomical location and their role in the management of the patient. RESULTS: Planar images showed a total number of 81 IMC nodes. SPECT-CT showed 74 nodes in the IMC territory and 14 mediastinal lymphatic nodes in 6 patients. Out of the 81 IMC nodes reported by planar images, seven corresponded to mediastinal nodes. Planar and hybrid images showed 110 and 130 axillary nodes, respectively. SPECT-CT showed additional findings in five patients: three infraclavicular and two supraclavicular nodes that were exactly located. One intramammary node was discarded by the SPECT-CT as a focal skin contamination. CONCLUSION: Mediastinal nodes are unexpected, but not uncommon findings that are important in the planning of SLN biopsy. SPECT-CT found more nodes than planar images, being able to separate mediastinal and IMC nodes, helping to exactly depict the SLN and its relations with anatomical structures.

Bilateral Ureteral Obstruction in Children after Appendectomy.

Acute renal failure due to bilateral ureteral obstruction is a rare complication after appendectomy in children. We report a case of bilateral ureteric obstruction in a 14-year-old boy nine days after surgery for an acute appendicitis. After saline-filling of the urinary bladder, transabdominal ultrasound demonstrated bilateral hydronephrosis of moderate degree. No abscess was found with CT but presence of millimetric stones on both distal ureters was shown, with bilateral calyceal dilatation. Cystoscopy revealed inflammatory changes in the bladder base. Following introduction of bilateral ureteric stents, there was rapid normalisation of urinary output and serum creatinine.

Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis.

OBJECTIVE: To estimate the incremental yield of detecting copy number variants (CNVs) by genomic microarray over karyotyping in fetuses with increased nuchal translucency (NT) diagnosed by first-trimester ultrasound. METHODS: This was a systematic review conducted in accordance with PRISMA criteria. We searched PubMed, Ovid MEDLINE and Web of Science for studies published between January 2009 and January 2015 that described CNVs in fetuses with increased NT, usually defined as ≥ 3.5 mm, and normal karyotype. Search terms included: fetal or prenatal, nuchal translucency or cystic hygroma or ultrasound anomaly, array comparative genomic hybridization or copy number variants, with related search terms. Risk differences were pooled to estimate the overall and stratified microarray incremental yield using RevMan. Quality assessment of included studies was performed using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. RESULTS: Seventeen studies met the inclusion criteria for analysis. Meta-analysis indicated an incremental yield of 5.0% (95% CI, 2.0-8.0%) for the detection of CNVs using microarray when pooling results. Stratified analysis of microarray results demonstrated a 4.0% (95% CI, 2.0-7.0%) incremental yield in cases of isolated NT and 7.0% (95% CI, 2.0-12.0%) when other malformations were present. The most common pathogenic CNVs reported were 22q11.2 deletion, 22q11.2 duplication, 10q26.12q26.3 deletion and 12q21q22 deletion. The pooled prevalence for variants of uncertain significance was 1%. CONCLUSION: The use of genomic microarray provides a 5.0% incremental yield of detecting CNVs in fetuses with increased NT and normal karyotype.

Rectus sheath haematoma: are there prognostic risk factors of haemodynamic instability motivating an early operative treatment?

PURPOSE: Rectus sheath haematoma (RSH) is an uncommon condition caused by lesion of the superior or inferior epigastric arteries or their branches or by rupture of the rectus muscle. Treatment is usually supportive; however, if haemodynamic compromise develops, intravascular embolisation or surgery may be required. Furthermore, in some cases, bleeding may be so conspicuous that it can determine the patient's death before an adequate treatment is performed. We performed a retrospective study on 78 consecutive patients with the diagnosis of RSH admitted to the General Surgery Unit of our hospital between January 2000 and December 2010 in order to identify possible prognostic risk factors that could affect the operational approach before the onset of haemodynamic instability. METHODS: Demographic characteristics, patient history, laboratory and diagnostic imaging examinations were investigated. The variables considered were: gender, age, anti-coagulation or anti-platelet therapy, trauma, international normalised ratio (INR) and bleeding time in the first 72 h of observation and concomitant diseases. The data were used for statistical analysis. RESULTS: Sixty patients received a conservative treatment, while 18 underwent operative treatment for haemodynamic instability (embolisation in 2 patients and surgery in 16 patients). Three of these 18 patients (17 %) died for consumption coagulopathy after surgery. None of the variables included in the univariate statistical analysis was significant (p = ns). CONCLUSION: Ultrasonography or computed tomography are the most common methods used to establish the diagnosis of RSH, so it is no longer a diagnostic dilemma. Most patients can be treated conservatively and an operative treatment is justified only in case of haemodynamic instability. Our retrospective study could not identify any prognostic risk factor of haemodynamic instability in RSH. We believe that only a close observation of the patients with RSH and "common sense" can prevent a possible fatal outcome.

Focus on abdominal rectopexy for full-thickness rectal prolapse: meta-analysis of literature.

BACKGROUND: Laparoscopic rectopexy to treat full-thickness rectal prolapse has proven short-term benefits, but there are few long-term follow-up and functional outcome data available. Using meta-analysis techniques, this study was designed to evaluate long-term results of open and laparoscopic abdominal procedures to treat full-thickness rectal prolapse in adults. METHODS: A literature review was performed using the National Library of Medicine's PubMed database. All articles on abdominal rectopexy patients with a follow-up longer than 16 months were considered. The primary end point was recurrence of rectal prolapse, and the secondary end points were improvement in incontinence and constipation. A random effect model was used to aggregate the studies reporting these outcomes, and heterogeneity was assessed. RESULTS: Eight comparative studies, consisting of a total of 467 patients (275 open and 192 laparoscopic), were included. Analysis of the data suggested that there is no significant difference in recurrence, incontinence and constipation improvement between laparoscopic abdominal rectopexy and open abdominal rectopexy. Considering non-comparative trials, the event rate for recurrence was similar in open and laparoscopic suture rectopexy studies and in open and laparoscopic mesh rectopexy trials. Improvement in constipation after the intervention was not statistically significant except for open mesh repair; postoperative improvement in incontinence was statistically significant after laparoscopic procedures and open mesh rectopexy. CONCLUSIONS: Laparoscopic abdominal rectopexy is a safe and feasible procedure, which may compare equally with the open technique with regard to recurrence, incontinence and constipation. However, large-scale randomized trials, with comparative, strong methodology, are still needed to identify outcome measures accurately.

[Final voluntary assessment for Traumatology and Orthopaedic Surgery medical residents: a report on the results and a look at the future]. / Evaluación final voluntaria para médicos residentes de Cirugía Ortopédica y Traumatología: balance de resultados y mirada al futuro.

INTRODUCTION: The idea of establishing an examination that accredits the training of the specialists in orthopaedic surgery at the end of their educational period as residents is subject to controversy. With the aim of encouraging the development of this examination, the present members of the National Commission of the Specialty of Orthopaedics (CNE) have reviewed the results obtained in previous examination. MATERIALS AND METHODS: The results of the voluntary final exam for Orthopaedics residents, and of the surveys of participant opinions for the years 2006 to 2011 are presented. RESULTS: The total number of participants was 231, growing from 19 in 2005, to 71 in 2011. The overall mean score in the period reviewed (2006-2011) was 6.72 out of 10 points. In these 6 years, 9 participants failed (4.25%). The mean score for the test was 7.57. The overall mean score of the oral exam was 6.57. The worst results were obtained in the general knowledge section of the oral examination. Nobody has ever failed the section on reconstruction of the lower extremity. The upper extremity section in the oral examination achieves the best average results. DISCUSSION: The examination has established its place in the structure of orthopaedic resident training in our country, even without making it official by the Administration. We must positively acknowledge those candidates who chose to take the examination and be evaluated by their peers in order to prove their qualification and distinction. This recognition will be the best encouragement for future generations.

Coexistence of two different types of lymphoma in a patient with Sjögren's syndrome. The usefulness of the PET-CT.

Sjögren syndrome is a chronic systemic autoimmune disease in which there is an increased risk of developing non-Hodgkin's lymphoma. Neoplastic lung involvement and the coexistence of different histological types of lymphoma are uncommon in these patients. These patients frequently have associated infectious processes, most of them due to oral candidiasis. When there is immunodeficiency, the hematogenous spread of the fungus may affect the lungs. We present the case of a female patient diagnosed with follicular non- Hodgkin lymphoma within the context of long-term Sjögren syndrome. In addition to the neoplastic nodal and splenic disease, the PET-CT study showed extensive lung involvement. Due to suspicion of a false positive result for pulmonary Candida infection, antifungal treatment was initiated, with no response. A further histological study showed the presence of a second and different type of lymphoma.