Multidisciplinary management of a large microcystic congenital pulmonary airway malformation: case report and literature review.

INTRODUCTION: Congenital pulmonary airway malformations (CPAMs) are rare sporadic lesions frequently associated with poor fetal prognosis. Type 3 CPAMs are characterized by small hyperechogenic cysts (<5 mm). Hydrops often develops secondarily, and the fetal survival rate is approximately 5% in this setting. CASE PRESENTATION: We present a case of a large type 3 CPAM complicated by fetal hydrops. The lesion was detected at 19 gestational weeks (GW) and confirmed by fetal MRI at 29 GW. At 22 GW, a course of maternal steroids was given as a possible treatment of type 3 CPAM. Peritoneal-amniotic shunt was placed twice to reduce fetal ascites, with unsatisfactory results. Similarly, polyhydramnios was relieved by two amnioreductions, but redeveloped soon after. A baby girl was delivered spontaneously at 33 GW and received a two-stage partial lobectomy in the first three months of life. Desaturations necessitated challenging invasive oscillatory ventilation between stages. Her outcome is unexpectedly positive and she may expect a good quality of life. She now approaches one year of age, with near-to-normal growth and developmental milestones. DISCUSSION: Type 3 CPAMs complicated by fetal hydrops are associated with high perinatal mortality. While open fetal surgery remains a viable option in select specialist centers, antenatal interventions are typically ineffective. The survival of this infant can be attributed to prenatal management and early postnatal surgical intervention. The lack of guidelines for ventilation in this setting was a significant challenge for neonatal intensivists. Multidisciplinary vigilance and collaboration with frequent specialist follow ups were the key to success for both mother and child.

Parotid gland pleomorphic adenoma re-operations with regard to patient and surgeon satisfaction: what can be improved?

BACKGROUND: Surgery, the treatment of choice for parotid pleomorphic adenoma (PA), is associated with facial nerve palsy and decreased quality of life. Re-operation for PA recurrence (rPA) significantly increases these risks and constitutes a dilemma for both patient and surgeon. Factors influencing the success of re-operation, as well as the self-reported satisfaction of both sides, have yet to be addressed in the literature. This study aims to improve upon the decision-making schedule in PA re-operations, based on patient expectations, imaging, and concordance with the first operative report (FOpR). METHODS: Seventy-two rPAs treated in a single tertiary center were collected and analyzed. The FOpRs and pre-operative imaging were divided according to defined criteria into accurate and non-accurate categories. The re-operative field and course were categorized as anticipated or unanticipated. The re-operation was categorized as satisfactory or unsatisfactory for both the patient and the surgeon. RESULTS: The accuracy of FOpRs and pre-operative imaging was 36.1% and 69.4%, respectively. Re-operative courses were: 36.1% anticipated and 63.9% unanticipated. The most frequently omitted data were: presence of satellite tumors (9.7%), and amount of removed parenchyma (9.7%). Variables that most commonly affected FOpR non-accuracy were: tumor size (Chi2(1)=59.92; p < 0.001) and capsule condition (Chi2(1)=29.11; p < 0.001). There was no significant relationship between FOpR accuracy and re-operative course (Chi2(1)=1.14; p = 0.286), patient satisfaction (Chi2(1)=1.94; p = 0.164) or surgeon satisfaction (Chi2(1)=0.04; p = 0.837). Pre-operative imaging (Chi2(1)=36.73; p < 0.001) had the greatest impact on surgeon satisfaction. CONCLUSION: Accurate pre-operative imaging impacted surgeon satisfaction. The impact of the FOpR on re-operation technicalities and patient satisfaction was minor. Imaging precision should be improved to streamline the decision-making process of PA re-operation. This article proposes suggestions for a future decision-making algorithm as a starting point for a prospective study.Key messagesAccurate pre-operative imaging impacts both surgeon and patient satisfaction.There is no significant relationship between the accuracy of the first operative report and surgeon and patient satisfaction.There is a statistically significant relationship between patient and surgeon satisfaction.

SGLT2 Inhibitors in Type 2 Diabetes Mellitus and Heart Failure-A Concise Review.

The incidence of both diabetes mellitus type 2 and heart failure is rapidly growing, and the diseases often coexist. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption-resulting in glycosuria-and therefore improving glycemic control. Recent trials have proven that SGLT2i also improve cardiovascular and renal outcomes, including reduced cardiovascular mortality and fewer hospitalizations for heart failure. Reduced preload and afterload, improved vascular function, and changes in tissue sodium and calcium handling may also play a role. The expected paradigm shift in treatment strategies was reflected in the most recent 2021 guidelines published by the European Society of Cardiology, recommending dapagliflozin and empagliflozin as first-line treatment for heart failure patients with reduced ejection fraction. Moreover, the recent results of the EMPEROR-Preserved trial regarding empagliflozin give us hope that there is finally an effective treatment for patients with heart failure with preserved ejection fraction. This review aims to assess the efficacy and safety of these new anti-glycemic oral agents in the management of diabetic and heart failure patients.

Can Overnutrition Lead to Wasting?-The Paradox of Diabetes Mellitus in End-Stage Renal Disease Treated with Maintenance Hemodialysis.

BACKGROUND: The population of end-stage renal disease (ESRD) patients with diabetes mellitus (DM) may be at increased risk of protein energy wasting (PEW). The aim of the study was to investigate the impact of DM on selected indicators of PEW in the ESRD population that was undergoing maintenance hemodialysis (MHD). METHODS: A total of 515 MHD patients were divided into two subgroups with and without DM. The evaluation of diet composition, Charlson Comorbidity Index (CCI), SGA, and laboratory and BIS analyses were performed. All-cause and cardiovascular mortality was recorded. RESULTS: DM patients had lower albumin (3.93 (3.61-4.20) vs. 4.10 (3.80-4.30) g/dL, p < 0.01), total cholesterol (158 (133-196) vs. 180 (148-206) mg/dL, p < 0.01), and creatinine (6.34 (5.08-7.33) vs. 7.12 (5.70-8.51) mg/dL, p < 0.05). SGA score (12.0 (10.0-15.0) vs. 11.0 (9.0-13.0) points, p < 0.001), BMI (27.9 (24.4-31.8) vs. 25.6 (22.9-28.8) kg/m2, p < 0.001), fat tissue index (15.0 (11.4-19.6) vs. 12.8 (9.6-16.0) %, p < 0.001), and overhydration (2.1 (1.2-4.1) vs. 1.8 (0.7, 2.7) L, p < 0.001) were higher in the DM group. Increased morbidity, reflected in the CCI and mortality-both all-cause and cardiovascular-were observed in DM patients. CONCLUSIONS: Hemodialysis recipients with DM experience overnutrition with a paradoxically higher predisposition to PEW, expressed by a higher SGA score and lower serum markers of nutrition. This population is also more comorbid and is at higher risk of death, including from cardiovascular causes.

Expression of p16Ink4a protein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course.

AIMS: The aim of the study is to correlate p16Ink4a expression with the clinical courses of pleomorphic adenoma (PA), its malignant transformation (CaexPA) and treatment outcomes. METHODS: Retrospective analysis (1998-2019) of 47 CaexPA, 148 PA and 22 normal salivary gland samples was performed. PAs were divided into two subsets: clinically 'slow' tumours characterised by stable size or slow growth; and 'fast' tumours with rapid growth rate. RESULTS: Positive p16Ink4a expression was found in 68 PA and 23 CaexPA, and borderline expression in 80 and 20, respectively. All 22 (100%) normal salivary gland samples presented with no p16Ink4a expression. Significant difference in p16Ink4a expression was observed between normal tissue, PA and CaexPA (χ2 (4)=172,19; p=0.0001). The PA clinical subgroups were also evaluated separately, revealing additional statistical relations: 'fast' PA and CaexPA differed significantly in p16Ink4a expression (χ2 (2)=8.06; p=0.01781) while 'slow' PA and CaexPA did not (χ2 (2)=3.09; p=0.2129). 3-year, 5-year and 10-year survival among p16Ink4a positive CaexPA patients was 100%, 90.56% and 60.37%, respectively, and in CaexPA patients with borderline p16Ink4a expression was 90.0%, 73.64% and 22.20%, respectively. Statistically significant difference between expression pattern and survival rate was observed (F Cox test - F (16, 24)=2.31; p=0.03075). CONCLUSIONS: Our study confirms no p16Ink4a expression in normal tissue, but reveals differences in expression between 'fast' and 'slow' PA. We suggest that p16Ink4a overexpression is connected to PA proliferation and subsequent malignant transformation to CaexPA. Borderline p16Ink4a staining correlates with worse prognosis of CaexPA.

Is the 3D exoscope better than the surgical microscope in parotid surgery: a prospective, randomized single-center study.

BACKGROUND: High-definition, three-dimensional (3D) exoscopes are being used to perform a growing number of head and neck surgeries. However, the use of the 3D exoscope in parotid gland surgery has not been previously described. Our initial experience with the VITOM 3D exoscope in the surgical treatment of parotid gland tumors is detailed here. METHODS: We made a prospective study of patients with benign parotid gland tumors indicated for surgical resection. Between January and December 2018, patients were randomly assigned to undergo surgery assisted with the VITOM 3D system (n = 31) or an operating microscope (n = 40). Visualization quality (greater auricular nerve, digastric muscle, tragal pointer), operating time, conversion rates, and surgical outcomes were compared. RESULTS: A total of 71 patients underwent superficial (n = 18) or total parotidectomy (n = 53). No exoscope-related complications were observed. Five patients undergoing exoscope-guided deep lobe surgery required intraoperative conversion to a microscope. No differences were observed in the subjective quality of intraoperative visualization of key anatomical structures. However, a significantly higher percentage of patients in the exoscope group developed transient facial nerve paralysis (n = 9; 29% vs. n = 4, 10%). CONCLUSIONS: These findings suggest that the VITOM 3D is a valid visualization tool for parotid gland surgery, comparable to the operating microscope but with higher resolution 3D visualization, an increased degree of freedom of movement, and better ergonomics. However, the high rate of transient nerve palsy, possibly related to decreased depth perception and the brief learning curve, merits further investigation.

Aspects of the Tumor Microenvironment Involved in Immune Resistance and Drug Resistance.

The tumor microenvironment (TME) is a complex and ever-changing "rogue organ" composed of its own blood supply, lymphatic and nervous systems, stroma, immune cells and extracellular matrix (ECM). These complex components, utilizing both benign and malignant cells, nurture the harsh, immunosuppressive and nutrient-deficient environment necessary for tumor cell growth, proliferation and phenotypic flexibility and variation. An important aspect of the TME is cellular crosstalk and cell-to-ECM communication. This interaction induces the release of soluble factors responsible for immune evasion and ECM remodeling, which further contribute to therapy resistance. Other aspects are the presence of exosomes contributed by both malignant and benign cells, circulating deregulated microRNAs and TME-specific metabolic patterns which further potentiate the progression and/or resistance to therapy. In addition to biochemical signaling, specific TME characteristics such as the hypoxic environment, metabolic derangements, and abnormal mechanical forces have been implicated in the development of treatment resistance. In this review, we will provide an overview of tumor microenvironmental composition, structure, and features that influence immune suppression and contribute to treatment resistance.

Multifaceted Sexual Dysfunction in Dialyzing Men and Women: Pathophysiology, Diagnostics, and Therapeutics.

Patient survival continues to increase with the growing quality of dialysis and management of chronic kidney disease (CKD). As such, chronic therapy must include considerations of quality of life (QOL), and this includes the disproportionate prevalence of sexual dysfunction (SD) in this patient population. This review aims to describe the pathophysiological and the psychosocial causes of SD with regard to renal replacement therapy, particularly hemo- and peritoneal dialysis. The differences in its manifestation in men and women are compared, including hormonal imbalances-and therefore fertility, libido, and sexual satisfaction-the experience of depression and anxiety, and QOL. The impact of comorbidities and the iatrogenic causes of SD are described. This review also presents validated scales for screening and diagnosis of SD in CKD patients and outlines novel therapies and strategies for the effective management of SD. Increased prevalence of CKD invariably increases the number of patients with SD, and it is crucial for health care professional teams to become familiar with the clinical tools used to manage this sensitive and under-quantified field. As a known predictor of QOL, sexual function should become a point of focus in the pursuit of patient-centered care, particularly as we seek to achieve as "normal" a life as possible for individuals who receive dialysis.

SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment.

The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002-2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic.

"A case report: Co-occurrence of cerebral amyloid angiopathy and multiple sclerosis".

Cerebral amyloid angiopathy (CAA) is a chronic pathological condition characterized by progressive accumulation of amyloid protein in the wall of cerebral blood vessels, both leptomeningeal and cortical. That may result in the development of such conditions as microaneurysms, hemorrhagic, ischaemic brain injury and contribute to cognitive impairment. We herein report a case of Iowa-type hereditary cerebral amyloid angiopathy (CAA) mutation diagnosed with MS. The family of the reported patient had performed genetic testing due to the history of intracerebral hemorrhage. Sequence analysis of exon 17 of the APP gene showed the presence of the D694N g.275272 G > A (c.2080 G > A) mutation, which caused the substitution of aspartate for aspargine at position 694 of APP. Alike the discussed patient, this mutation has been found in other family members in an autosomal dominant pattern of inheritance. Contrary to the rest of the family, the reported patient has been diagnosed with multiple sclerosis based on McDonald criteria. Recent studies shed light on the possible link between the APP accumulation and MS progression. It has been indicated that amyloid can prove a vital role in neuroimmunology, whereas the accumulation of APP in the CNS has been suggested to be a potential biomarker for the progression of MS. Moreover, the amyloid positron-emission tomography (amyloid-PET) has been demonstrated to serve as a diagnostic tool for establishing the degree of demyelination and remyelination in MS. Even though, one swallow does not make a summer, this finding would be another step forward in the understanding of pathological processes underlying the pathogenesis of MS.

The impact of accurate documentation of parotid tumor operative reports on secondary surgical procedure.

OBJECTIVE: To develop a comprehensive operative report schema based on the accuracy of primary operative reports (OpR) assessed on a department's experience with parotid gland tumor re-operations. DESIGN: Retrospective cross-sectional study. SETTING: A tertiary referral center, the Department of Otolaryngology and Laryngological Surgery, Poznan University of Medical Sciences, Poland from 2008 to 2017. SUBJECTS: Out of 1154 surgeries, 71 patients underwent reoperation. Their OpR were categorized into accurate and non-accurate, and re-operation field and re-operation course were categorized as anticipated or unanticipated, according to defined criteria. INTERVENTION: None Main outcome measures: The impact of accuracy of the first OpR on re-operation course. RESULTS: In this series, OpR were 39% (14/36) accurate, 61% (22/36) non-accurate. Re-operation fields were 16% (11/71) anticipated, 37% (26/71) unanticipated. Re-operation courses were 37% (26/71) anticipated, 63% (45/71) unanticipated. An anticipated re-operation course followed 20% (5/26) of accurate and 20% (5/26) of non-accurate primary OpR. An unanticipated re-operation course followed 20% (9/45) of accurate and 40% (18/45) of non-accurate OpR. There is no significant relationship between the re-operation course and accuracy of the first OpR (Chi2(1)=0.69; p=0.40466). The most common variable that affected non-accuracy of the OpR was facial nerve function after surgery (6/12). CONCLUSIONS: The operative report should be based on clear criteria, robust classification and comprehensive protocol. This will improve follow-up and facilitate the planning of re-operation.

Salivary Gland Pleomorphic Adenomas Presenting With Extremely Varied Clinical Courses. A Single Institution Case-Control Study.

OBJECTIVE: Pleomorphic adenomas (PAs) with divergent clinical behavior, differing from the vast majority of PAs, were distinguished. "Fast" PAs are characterized by an unexpectedly short medical history and relatively rapid growth. The reference group consisted of "slow" PAs with very stable biology and long-term progression. We divide the PA group as a whole into three subsets: "fast," "normal," and "slow" tumors. Our goal is a multifactorial analysis of the "fast" and "slow" PA subgroups. METHODS: Consecutive surgeries in a tertiary referral center, the Department of Otolaryngology and Laryngological Surgery, Poznan University of Medical Sciences, Poland, were carried out between 2002 and 2011. Out of 1,154 parotid tumors, 636 (55.1%) were PAs. The data were collected prospectively in collaboration with the Polish National Registry of Benign Salivary Gland Tumors. The main outcome measure was the recurrence rate in "fast" and "slow" PA subgroups. All surgical qualifications and surgeries were performed by two experienced surgeons. RESULTS: Slow PAs, compared to fast PAs, presented in older patients (53.25 ± 15.29 versus 47.92 ± 13.44 years). Multifactor logistic regression analysis with recurrence (yes/no) as the outcome variable, fast/slow as the predictor variable and age, gender, margin, FN status as covariates showed that fast PAs were significantly predicting recurrence vs. slow PAs (p = 0.035). Fast PAs were increasing the risk of PAs 10-fold vs. slow PAs, exp ß = 10.20, CI95 [1.66; 197.87]. The variables impacting relapse were recent accelerated growth of the tumor OR = 3.35 (SE = 0.56), p = 0.030, positive margins OR = 7.18 (SE = 0.57), p < 0.001, incomplete or bare capsule OR = 9.91 (SE = 0.53), p = 0.001 and location III OR = 3.12 (SE = 0.53), p = 0.033. In the multivariate model only positive margin was selected as the best predictor of relapse, OR = 5.01 (SE = 0.60), p = 0.007. CONCLUSIONS: The simple clinical aspect of slow or fast PA progression is of great practical importance and can constitute a surrogate of the final histopathological information that is derived from the surgical specimen. The slow or fast nature of the PA to some extent indicates prognostic features such as recurrence risk. This finding requires correlation with histological and molecular features in further stages of research.

NK cells in patients with chronic rhinosinusitis show decreased maturity and limited expression of functional receptors.

Chronic rhinosinusitis is an inflammatory process of the mucous membrane of the nasal cavity and paranasal sinuses, presenting with two phenotypes that differ in symptoms and inflammatory profiles: either with or without polyps. Natural killer (NK) cells are involved in both the innate and acquired immune response, and their function may be limited under pathological conditions, leading to polyp formation. We determined NK cell involvement and maturity in chronic rhinosinusitis, by determining the percentage of NK cells in polyps, nasal mucosa, and in the peripheral blood. Material was obtained from 49 patients with chronic rhinosinusitis (36 with polyps, 13 without polyps), and 15 control patients. Flow cytometry was used to immunophenotype NK cells, and the expression of selected functional receptors was evaluated. NK cells were found to be increased in polyp tissue versus peripheral blood and nasal mucosa. NK cell maturation differed significantly with predominance of a cytotoxic phenotype (CD11b+/27-) in peripheral blood, compared with a regulatory/tolerogenic phenotype (CD11+/-/ 27+) in tissue material. These findings demonstrate the involvement of NK cells in the inflammatory process of chronic rhinosinusitis. Decreased expression of activating receptors in the analyzed groups may also indicate the presence of modifying agents. Disorders of the maturation process of NK cells may be an important element in the etiopathogenesis of chronic rhinosinusitis with and without polyps.