Acetylcholinesterase inhibitors are ineffective in MuSK-antibody positive myasthenia gravis: Results of a study on 202 patients.

BACKGROUND: Myasthenia gravis (MG) with MuSK antibodies (MuSK-MG) represents a distinct subtype with different responses to treatments compared to patients with AChR antibodies, especially in terms of tolerance to acetylcholinesterase inhibitors (AChEI). However, AChEI are often used as first line symptomatic treatment in MuSK-MG, despite reports that they are poorly tolerated, seldom effective or even deleterious. METHODS: We analyzed demographic, clinical and therapeutic responses and side-effects in the large cohort of 202 MuSK-MG patients cared for at the MG Clinic of Azienda Ospedaliero-Universitaria Pisana. RESULTS: 165 patients had received AChEI at first evaluation. Only 7/165 patients (4.2%) reported an initial clinical benefit. Conversely, 76.9% of patients reported at least one side effect, most commonly neuromuscular hyperexcitability (68.4%), gastrointestinal (53.9%) and neurovegetative (35.8%) disturbances. 56 (33.9%) patients reported a concomitant worsening of muscle weakness and twelve patients (7.3%) suffered a cholinergic crisis. According to these patients, the severity of cholinergic side effects was greater at higher doses of AChEI, but side effects occurred regardless of the dose administered and ceased once the drug was discontinued. CONCLUSIONS: This is the largest population of MuSK-MG patients reported for perceived responsiveness and tolerance to AChEI treatment. Our obervations strongly suggest avoiding this treatment in MuSK-MG.

Absorbed dose evaluation of a blood irradiator with alanine, TLD-100 and ionization chamber.

Irradiation of blood bags using X-ray irradiators and dosimetry services are required to ensure uniform dose levels in the range 25-50 Gy to prevent Transfusion Associated Graft versus Host Disease (TA-GvHD). An absorbed dose characterization of a Raycell MK2 X-Irradiator was performed using three different dosimetric systems. Results showed a dosimetric accuracy of the ionization chamber together with the Alanine dosimeter. TLDs measurements exhibited a small overestimation by 4% of the absorbed dose. The Dose Uniformity Ratio (DUR), between maximum and minimum dose levels in the canister, was in good agreement with the manufacturer specifications (≤1.5).

HOCl Rapidly Kills Corona, Flu, and Herpes to Prevent Aerosol Spread.

The COVID-19 pandemic has escalated the risk of SARS-CoV-2 transmission in the dental practice, especially as droplet-aerosol particles are generated by high-speed instruments. This has heightened awareness of other orally transmitted viruses, including influenza and herpes simplex virus 1 (HSV1), which are capable of threatening life and impairing health. While current disinfection procedures commonly use surface wipe-downs to reduce viral transmission, they are not fully effective. Consequently, this provides the opportunity for a spectrum of emitted viruses to reside airborne for hours and upon surfaces for days. The objective of this study was to develop an experimental platform to identify a safe and effective virucide with the ability to rapidly destroy oral viruses transported within droplets and aerosols. Our test method employed mixing viruses and virucides in a fine-mist bottle atomizer to mimic the generation of oral droplet-aerosols. The results revealed that human betacoronavirus OC43 (related to SARS-CoV-2), human influenza virus (H1N1), and HSV1 from atomizer-produced droplet-aerosols were each fully destroyed by only 100 ppm of hypochlorous acid (HOCl) within 30 s, which was the shortest time point of exposure to the virucide. Importantly, 100 ppm HOCl introduced into the oral cavity is known to be safe for humans. In conclusion, this frontline approach establishes the potential of using 100 ppm HOCl in waterlines to continuously irrigate the oral cavity during dental procedures to expeditiously destroy harmful viruses transmitted within aerosols and droplets to protect practitioners, staff, and other patients.

A deep learning classifier for digital breast tomosynthesis.

PURPOSE: To develop a computerized detection system for the automatic classification of the presence/absence of mass lesions in digital breast tomosynthesis (DBT) annotated exams, based on a deep convolutional neural network (DCNN). MATERIALS AND METHODS: Three DCNN architectures working at image-level (DBT slice) were compared: two state-of-the-art pre-trained DCNN architectures (AlexNet and VGG19) customized through transfer learning, and one developed from scratch (DBT-DCNN). To evaluate these DCNN-based architectures we analysed their classification performance on two different datasets provided by two hospital radiology departments.DBT slice images were processed following normalization, background correction and data augmentation procedures. The accuracy, sensitivity, and area-under-the-curve (AUC) values were evaluated on both datasets, using receiver operating characteristic curves. A Grad-CAM technique was also implemented providing anindication of the lesion position in the DBT slice. RESULTS: Accuracy, sensitivity and AUC for the investigated DCNN are in-line with the best performance reported in the field. The DBT-DCNN network developed in this work showed an accuracy and a sensitivity of (90% ± 4%) and (96% ± 3%), respectively, with an AUC as good as 0.89 ± 0.04. Ak-fold cross validation test (withk = 4) showed an accuracy of 94.0% ± 0.2%, and a F1-score test provided a value as good as 0.93 ± 0.03. Grad-CAM maps show high activation in correspondence of pixels within the tumour regions. CONCLUSIONS: We developed a deep learning-based framework (DBT-DCNN) to classify DBT images from clinical exams. We investigated also apossible application of the Grad-CAM technique to identify the lesion position.

Acquired neuromyotonia in thymoma-associated myasthenia gravis: a clinical and serological study.

BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.

What is the optimal management of an intra-operative air leak in a colorectal anastomosis?

AIM: An airtight anastomosis on intra-operative leak testing has been previously demonstrated to be associated with a lower risk of clinically significant postoperative anastomotic leak following left-sided colorectal anastomosis. However, to date, there is no consistently agreed upon method for management of an intra-operative anastomotic leak. Therefore, we powered a noninferiority study to determine whether suture repair alone was an appropriate strategy for the management of an intra-operative air leak. METHOD: This is a retrospective cohort analysis of prospectively collected data from a tertiary care referral centre. We included all consecutive patients with left-sided colorectal or ileorectal anastomoses and evidence of air leak during intra-operative leak testing. Patients were excluded if proximal diversion was planned preoperatively, a pre-existing proximal diversion was present at the time of surgery or an anastomosis was ultimately unable to be completed. The primary outcome measure was clinically significant anastomotic leak, as defined by the Surgical Infection Study Group at 30 days. RESULTS: From a sample of 2360 patients, 119 had an intra-operative air leak during leak testing. Sixty-eight patients underwent suture repair alone and 51 underwent proximal diversion or anastomotic reconstruction. The clinically significant leak rate was 9% (6/68; 95% CI: 2-15%) in the suture repair alone arm and 0% (0/51) in the diversion or reconstruction arm. CONCLUSION: Suture repair alone does not meet the criteria for noninferiority for the management of intra-operative air leak during left-sided colorectal anastomosis. Further repair of intra-operative air leak by suture repair alone should be reconsidered given these findings.

Characterization of Self-Assembled Monolayers on a Ruthenium Surface.

We have modified and stabilized the ruthenium surface by depositing a self-assembled monolayer (SAM) of 1-hexadecanethiol on a polycrystalline ruthenium thin film. The growth mechanism, dynamics, and stability of these monolayers were studied. SAMs, deposited under ambient conditions, on piranha-cleaned and piranha + H2SO4 cleaned substrates were compared to monolayers formed on H-radical-cleaned Ru surfaces. We found that alkanethiols on H-radical-cleaned Ru formed densely packed monolayers that remained stable when kept in a nitrogen atmosphere. X-ray photoelectron spectroscopy (XPS) shows a distinct sulfur peak (BE = 162.3 eV), corresponding to metal-sulfur bonding. When exposed to ambient conditions, the SAM decayed over a period of hours.

High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society advise evaluating autoantibody positivity in first-degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the disease. The aim of this study was to determine the prevalence of beta-cell autoimmunity in FDRs of T1DM patients in Sardinia. METHODS: A total of 188 Sardinian families were recruited in collaboration between diabetes and pediatric units of university and district hospitals in Sardinia. The recruitment involved 188 patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies (Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43 Aabs-positive FDR. RESULTS: The prevalence of Aabs (any type of autoantibody, single or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53) were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55% (4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of HLA-DR and DQ loci showed that 89% of FDR carried moderate- to high-risk genotypes, with only 5 FDR with low-risk genotypes. CONCLUSIONS: The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.

Uracil-DNA glycosylases-structural and functional perspectives on an essential family of DNA repair enzymes.

Uracil-DNA glycosylases (UDGs) are evolutionarily conserved DNA repair enzymes that initiate the base excision repair pathway and remove uracil from DNA. The UDG superfamily is classified into six families based on their substrate specificity. This review focuses on the family I enzymes since these are the most extensively studied members of the superfamily. The structural basis for substrate specificity and base recognition as well as for DNA binding, nucleotide flipping and catalytic mechanism is discussed in detail. Other topics include the mechanism of lesion search and molecular mimicry through interaction with uracil-DNA glycosylase inhibitors. The latest studies and findings detailing structure and function in the UDG superfamily are presented.

What are 30-day postoperative outcomes following splenic flexure mobilization during anterior resection?

BACKGROUND: The aim of this study was to determine whether mobilization of the splenic flexure during anterior resection is associated with an increased number of complications. METHODS: This is a retrospective cohort analysis of all non-emergent anterior resections with anastomosis (open and laparoscopic) between January 2005 and December 2009 from the American College of Surgeons National Surgical Quality Improvement Program. Infectious, renal, and pulmonary adverse events as well as operative times were analyzed for cases with splenic flexure mobilization as compared to no mobilization. We then constructed multivariate models to identify risk factors for postsurgical adverse events. RESULTS: During the 5-year study period, 6,324 (57 %) open resections and 4,788 (43 %) laparoscopic resections were performed. Mobilization of the splenic flexure was associated with an increase in operating room time (204 vs 172 min, p < 0.0001). Although anastomotic leaks were not recorded, there was no difference in organ space infections (3.9 vs 3.7 %, p = 0.7) or return to operating room events between the two groups. However, patients who underwent splenic flexure mobilization had significantly more superficial surgical site infections (10.6 vs 8.4 %, p < 0.0002). Multivariate analysis accounting for laparoscopic or open surgery and standard preoperative and intraoperative variables demonstrated a persistent increase in superficial surgical site infections for patients with splenic flexure mobilization. CONCLUSIONS: Operating room times are longer and superficial surgical site infections are more common when the splenic flexure is mobilized. The absolute indications for splenic flexure mobilization should be addressed in further research.

Structure of the uracil complex of Vaccinia virus uracil DNA glycosylase.

Poxvirus uracil DNA glycosylases are the most diverse members of the family I uracil DNA glycosylases (UNGs). The crystal structure of the uracil complex of Vaccinia virus uracil DNA glycosylase (D4) was determined at 2.03 Å resolution. One uracil molecule was located in the active-site pocket in each of the 12 noncrystallographic symmetry-related D4 subunits. Although the UNGs of the poxviruses (including D4) feature significant differences in the characteristic motifs designated for uracil recognition and in the base-excision mechanism, the architecture of the active-site pocket in D4 is very similar to that in UNGs of other organisms. Overall, the interactions of the bound uracil with the active-site residues are also similar to the interactions previously observed in the structures of human and Escherichia coli UNG.

Do admissions and discharges to long-term care facilities influence hospital burden of Clostridium difficile infection?

BACKGROUND: Substantial geographical clustering of Clostridium difficile infection (CDI) outbreaks in hospitals in the USA have previously been demonstrated. AIM: To test the hypothesis that hospital burden of CDI is associated with admission from and discharge to long-term care facilities (LTCFs). METHODS: Hospital discharge data from 19 states in the USA were used to identify all patients discharged with a diagnosis of CDI from 1 January 2002 to 31 December 2004. For every hospital, the proportion of discharges with a diagnosis of CDI was calculated, and those above the 90th percentile were classified as 'high CDI' hospitals. We tested the association between this measure of hospital burden of CDI and the rates of admission from and discharges to LTCFs. We adjusted for other hospital level characteristics, case-complexity and local population characteristics. FINDINGS: We identified 38,372,951 discharges during the three-year study period. Of all discharges, 274,311 (0.71%) had a primary or secondary diagnosis of CDI. Hospitals had a mean CDI burden of 7.8 cases per 1000 discharges. High CDI hospitals (N = 610; 10.0%) had a mean CDI burden of 34.8 cases per 1000 discharges. Compared to other hospitals, high CDI hospitals were more likely to have a high proportion of admissions from or discharges to LTCFs. This association persisted after adjustments for other hospital characteristics, case-complexity, and area population characteristics. CONCLUSION: A high rate of admission from or discharge to LTCFs is associated with an increased hospital burden of CDI.

How often do patients return to the operating room after colorectal resections?

AIM: We sought to identify the rate of re-operation after an index colorectal surgical procedure and potential contributing risk factors. METHOD: This is a retrospective cohort study from the American College of Surgeons National Surgical Quality Improvement Program. We identified all patients who either returned or did not return to the operating room after any colorectal resection from January 2005 to December 2008. RESULTS: From a total cohort of 635, 265 patients included in the National Surgical Quality Improvement Program over the 4-year study period, we identified 54, 237 patients who underwent colorectal operations. A return to the operating room was coded in 5.4 ± 0.1% of non colorectal resection patients and 7.6 ± 0.2% of colorectal resection patients (P < 0.001). The multivariate model identified patients with postoperative diagnostic codes for abdominal cavity hernia or colostomy complication as having the highest odds of return to the operating room within 30 days. Patients returning to the operating room had longer length of stay and higher overall mortality compared with those patients who did not return to the operating room. CONCLUSION: Return to the operating room is a relatively common occurrence after colorectal resections, with an associated high rate of mortality. Given the association between return to the operating room and adverse patient outcomes, emphasis should be placed on determining strategies to reduce the need for return to the operating room.

[In vitro activity of voriconazole and other antifungal agents against clinical isolates of 138 Candida spp]. / Attivita in vitro del voriconazolo e di altri agenti antimicotici nei confronti di 138 isolati clinici di Candida spp.

Voriconazole is used for treating invasive Aspergillosis, Fusarium and Scedosporium infections as well as resistant candidiasis. It is referred to as a second generation triazole. The purpose of this study was to evaluate the concordance of the results of antifungal voriconazole susceptibility tests for yeast isolates, comparing the Sensititre YeastOne method, Atb Fungus 3 and Etest. In all, 138 yeast isolates (42 C. tropicalis, 36 C. glabrata, 14 C. albicans, 8 C. famata, 6 C. parapsilosis, 4 C. dubliniensis, 3 C. krusei, 3 C. lusitaniae, 2 C. zeylanoides, 20 Candida spp.) were tested for susceptibility to amphotericin B, flucytosine, fluconazole , itraconazole and voriconazole with Atb Fungus 3 method. The concordance between the Sensititre YeastOne method, Atm Fungus 3 and Etest for voriconazole was high (90%).

In vitro activity of tigecycline against multidrug-resistant Acinetobacter baumannii clinical isolates.

This survey was conducted to evaluate the in vitro activity of tigecycline against 50 isolates of multidrug-resistant (MDR) Acinetobacter baumannii. Isolates of A. baumannii were resistant to ciprofloxacin, chloramphenicol, imipenem, levofloxacin, piperacillin and piperacillin-tazobactam, but were always susceptible to colistin. MICs of tigecycline were determined by E-test in Mueller-Hinton agar. The results of the study showed that 50% of the A. baumannii strains were susceptible to tigecycline.

Predictors of Clostridium difficile colitis infections in hospitals.

Hospital-level predictors of high rates of 'Clostridium difficile-associated disease' (CDAD) were evaluated in over 2300 hospitals across California, Arizona, and Minnesota. American Hospital Association data were used to determine hospital characteristics associated with high rates of CDAD. Significant correlations were found between hospital rates of CDAD, common infections and other identified pathogens. Hospitals in urban areas had higher average rates of CDAD; yet, irrespective of geographic location, hospital rates of CDAD were associated with other infections. In addition, hospitals with 'high CDAD' rates had slower turnover of beds and were more likely to offer transplant services. These results reveal large differences in rates of CDAD across regions. Hospitals with high rates of CDAD have high rates of other common infections, suggesting a need for broad infection control policies.

Blastomyces dermatitidis of the perianal skin: report of a case.

Isolated fungal infections of the perianal skin are rare and their diagnosis is frequently overlooked. We report a case of a 78-year-old male patient who presented with a friable, violaceous, papulopustular lesion, with heaped-up edges along the anal verge. Biopsy revealed unicellular yeast consistent with blastomycosis. The patient was treated with itraconazole with resolution of this lesion. An extensive MEDLINE literature review from 1958 to the present indicates that this is an uncommon manifestation of cutaneous blastomycosis. A summary of the medical literature is presented with a review of the characteristics, diagnosis, and management of blastomycosis.

[Some behavioral characteristics of physicians desired by ambulatory patients. A pilot survey]. / Alcune caratteristiche comportamentali del medico desiderate dal paziente in ambito ambulatoriale. Indagine conoscitiva pilota.

AIMS: We must pay attention to character formation of Medical Doctors because it could build a good or bad relationship with colleagues and patients: it is not a merely "humanistic" goal but a necessary component of professional excellence. The first endpoint of this study is to identify how to improve the quality of the outpatient visit. MATERIALS AND METHODS: We tested a user-friendly questionnaire, distributed to 100 patients. RESULTS AND CONCLUSIONS: The most important behavioral characteristics desired by patients from physicians are: 1. to have the physician's attention without feeling hurried (such as without the physician answering a phone call during the office visit); 2. to have continuity of care even in the ambulatory setting; 3. to find a relationship of empathy, participation and sharing; 4. to have a peaceful relationship of collaboration with the nurses and other health care personnel; 5. to find the physician appropriately groomed and dressed; 6. to receive the full diagnosis with clarity and at the most appropriate moment of communication.

Causes of portal venous thrombosis in cirrhotic patients: the role of genetic and acquired factors.

OBJECTIVE AND METHODS: We compared frequencies of three common prothrombotic mutations (factor V Leiden, the G20210A mutation of the prothrombin gene, and homozygosity for C677T methylenetetrahydrofolate reductase) in 219 cirrhotic patients, 43 with and 176 without portal vein thrombosis (PVT). The following variables were related to PVT: prothrombin levels, platelet count, Child-Pugh classification, previous abdominal surgery, number of decompensation events, size of varices, red markers on varices, and sclerotherapy. All patients were followed up for a mean period of 18 months (range 10-30). RESULTS: Prothrombotic mutations were detected in 64 of the 219 cirrhotic patients (29.2%), at equal frequency in patients with or without PVT. At univariate analysis, PVT was associated with Child-Pugh classes B and C, signs of liver decompensation, large varices with red markings, sclerotherapy, and abdominal surgery. At multivariate analysis, PVT was associated with sclerotherapy [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.2-11] and previous surgery (OR 2.8, 95% CI 1.2-6.3). The combination of the two acquired factors increased the risk of PVT, whereas the combination of local with genetic defects did not. Only a single patient with genetic thrombophilia and without PVT at inclusion developed the complication during follow-up, concomitantly with the development of hepatocellular carcinoma. CONCLUSION: In cirrhotic patients prothrombotic mutations by themselves are not causative of PVT. Sclerotherapy and previous abdominal surgery favour the development of two-thirds of cases of PVT; in the remaining cases the pathogenesis remains elusive.