Breakthrough COVID-19 in people with multiple sclerosis on disease modifying treatments: Is it still a severe disease?

INTRODUCTION: Disease modifying treatments (DMTs) for multiple sclerosis (MS) are effective in preventing both relapses and disability progression. Highly effective treatments (HETs) are more effective than platform therapy in preventing confirmed disability progression (CDP), when used early. Infections may complicate HETs administration, and their prevention through vaccination is crucial in order to assure the safety of people with MS (pwMS). The aim of the present study is to describe the effect of MS DMTs on COVID-19 vaccination and the risk of breakthrough infection in a cohort of pwMS. MATERIALS AND METHODS: This is a monocentric retrospective observational study conducted at the MS center of the Guglielmo da Saliceto Hospital in Piacenza, Italy. One hundred and fifty-seven (157) pwMS who received two doses of the SARS-CoV-2 vaccine (with 80.3 % receiving a booster dose) were included in the study. RESULTS: fifty-six pwMS (35.7 %) were females, the mean age was 48.6 (SD: 12.87) years, and 59 (37.6 %) had at least one comorbidity. Twenty-five (15.9 %) breakthrough infections were observed, with 17 (68.0 %) classified as mild and 8 (32.0 %) as moderate. A multivariable linear regression model confirmed that B-cell suppressor DMTs and EDSS were factors associated with the latest antibody titre. Patients treated with B-cell suppressors exhibited a risk almost four times higher for breakthrough infections compared to other patients, with a hazard ratio (HR) of 3.72 (95 % CI: 1.50 - 9.27) (p = 0.005). CONCLUSIONS: B-cell suppressor DMTs are associated with the risk of breakthrough COVID-19 in our cohort, but vaccination fully protected pwMS against severe breakthrough disease.

Ultrasonographic characterization of parametrial endometriosis: a prospective study.

OBJECTIVE: To study the ultrasonographic diagnostic accuracy and characteristics of parametrial endometriosis comprehensively. DESIGN: This prospective study enrolled patients with suspected deep endometriosis (DE) scheduled for laparoscopic surgical treatment. Preoperative ultrasonographic examinations were performed following the International Deep Endometriosis Analysis criteria. This study aimed to evaluate the presence of parametrial endometriosis and its ultrasonographic characteristics, using surgical diagnosis as the reference standard. Additionally, indirect signs of DE and concomitant DE nodules associated with parametrial involvement were identified, assessing their predictive significance in the anterior, lateral, and posterior parametrial areas. SETTING: Referral institution for endometriosis. PATIENTS: Patients with suspected DE scheduled for surgical treatment. INTERVENTIONS: Standardized preoperative ultrasonographic examination. MAIN OUTCOME MEASURES: The diagnostic accuracy of transvaginal ultrasound in identifying parametrial endometriosis, including sensitivity and specificity, and the ultrasonographic characteristics of parametrial nodules, prevalence in distinct parametrial areas, and associations with indirect DE signs and concomitant DE nodules. RESULTS: Surgical confirmation of parametrial nodules was observed in 105 of 545 patients (left, 18.5; right, 17.0%). Transvaginal ultrasound demonstrated a sensitivity of 77.1% (95% confidence interval, 68.0%-84.8%) and specificity of 99.1% (95% confidence interval, 67.7%-99.8%). Parametrial nodules typically exhibited characteristics such as a mild hypoechoic appearance (83.6%), starry morphology (74.7%), irregular margins (70.2%), and low vascularization. The posterior parametrial region was the most common location (52.2%), followed by the lateral (41.0%) and anterior (6.8%) parametrial regions. Concomitant DE nodules in the rectum (63.5%) and infiltrating the rectovaginal septum (56.5%) were significantly more prevalent in patients with parametrial involvement. Indirect DE signs, such as the ovaries fixed to the uterine wall (71.8%) and the absence of a posterior sliding sign (51.8%), were also more common in women with parametrial nodules. Hydronephrosis, although relatively uncommon in patients with parametrial involvement (8.2%), was largely detected in lateral parametrial nodules (70.0%). CONCLUSIONS: This study represents a systematic ultrasonographic characterization of parametrial endometriosis. Specifically, it comprehensively assesses the diagnostic accuracy of transvaginal ultrasound in identifying parametrial involvement within a sizable cohort of patients with preoperative suspicion of DE. CLINICAL TRIAL REGISTRATION NUMBER: NCT06017531.

Ultrasonographic Findings Indirectly Predicting Parametrial Involvement in Patients with Deep Endometriosis: The ULTRA-PARAMETRENDO I Study.

STUDY OBJECTIVE: To evaluate ultrasonographic findings as a first-line imaging tool to indirectly predict the presence of parametrial endometriosis (PE) in women with suspected deep endometriosis (DE) undergoing surgery. DESIGN: Retrospective analysis of a prospectively collected database (ULTRA-PARAMETRENDO I study; NCT05239871). SETTING: Referral center for DE. PATIENTS: Consecutive patients undergoing laparoscopic surgery for DE. INTERVENTIONS: Preoperative transvaginal ultrasonography was done according to the International Deep Endometriosis Analysis consensus statement. A stepwise forward regression analysis was performed considering the simultaneous presence of DE nodules and the following ultrasonographic indirect signs of DE: diffuse adenomyosis, endometriomas, ovary fixed to the lateral pelvic wall or the uterine wall, absence of anterior/posterior sliding sign, and hydronephrosis. The gold standard for the presence of PE was surgery with histologic confirmation. MEASUREMENTS AND MAIN RESULTS: Of 1079 patients, 212 had a surgical diagnosis of PE (left: 18.5%; right: 17.0%; bilateral: 15.9%). The obtained prediction model (χ2 = 222.530; p <.001) for PE included, as independent indirect DE signs presence of hydronephrosis (odds ratio [OR] = 14.5; p = .002), complete absence of posterior sliding sign (OR = 3.3; p <.001), presence of multiple endometriomas per ovary (OR = 3.0; p = .001), and ovary fixation to the uterine wall (OR = 2.4; p <.001); as independent concomitant DE nodules, presence of uterosacral nodules with the largest diameter >10 mm (OR = 3.2; p <.001), presence of rectal endometriosis with the largest diameter >25 mm (OR = 2.3; p = .004), and rectovaginal septum infiltration (OR = 2.3; p = .003). The optimal diagnostic balance was obtained considering at least 2 concomitant DE nodules and at least 1 indirect DE sign (area under the curve 0.75; 95% confidence interval, 0.72-0.79). CONCLUSION: Specific indirect ultrasonographic findings should raise suspicion of PE in women undergoing preoperative assessment for DE. The suspicion of parametrial invasion may be critical to address patients to expert leading centers, where proper diagnosis and surgical treatment for PE can be performed.

The Impact of Highly Effective Treatment in Pediatric-Onset Multiple Sclerosis: A Case Series.

INTRODUCTION: Pediatric-onset multiple sclerosis (POMS) is characterized by high inflammatory disease activity. Our aim was to describe the treatment sequencing and report the impact highly effective disease-modifying treatment (HET) had on disease activity. MATERIALS AND METHODS: Five consecutive patients with POMS were administered HET following lower efficacy drug or as initial therapy. Data on treatment sequencing, relapses and MRIs were collected during the follow-up. RESULTS: Our patients had an average age of 13.8 years (range 9-17) at diagnosis and 13.4 years (range 9-16) at disease onset, and 2/5 (40%) POMS were female. The pre-treatment average annualized relapse rate was 1.6 (range 0.8-2.8), and the average follow-up length was 5 years (range 3-7). A total of 2/5 (40%) patients were stable on HET at initial therapy, and 3/5 (60%) required an escalation to more aggressive treatment, even if two of them had been put on HET as initial treatment. Four out of five patients (80%) had No Evidence of Disease Activity-3 status (NEDA-3) at an average follow-up of 3 years (range 2-5). CONCLUSION: It has been observed that in a recent time period all the cases had prompt diagnosis, early HET or escalation to HET with a good outcome in 80% of the cases.

A "Post-mortem" of COVID-19-associated stroke: a case-control study.

OBJECTIVES: To assess whether COVID-19 could be a concurrent factor in the genesis and/or worsening of stroke and to provide data on COVID-19 -associated stroke patients during the first pandemic wave and comparative data on COVID-19 negative stroke patients in the same period. MATERIALS AND METHODS: This is a retrospective, observational, case-control, single centre study, carried out in a General Hospital in northern Italy. Sixty-three consecutive stroke patients were included, COVID-19-associated stroke was classified as cases and non COVID-19-associated stroke as controls. RESULTS: A total of 19/63 (28.8%) had a COVID-19-associated stroke, 11 /63 (17.5%) were haemorrhagic and 52/63 (82.5%) ischaemic. COVID-19-associated strokes were more severe (p-value 0.019) and had a higher risk of severe disability and/or death (OR 3.79, CI 95%: 1.21-11.93, p-value 0.19). The COVID-19-associated stroke patients with onset during hospitalization for COVID-19 had a more severe stroke than patients with COVID-19 onset during hospitalization for stroke (p-value 0.019). CONCLUSION: Although no relationship was observed between the stroke aetiology and COVID-19, intriguingly, COVID-associated stroke turned out to be more severe and disabling. Hopefully, further studies will provide more data and help in the management of this emerging population.

Lung involvement correlates with disability in MS patients with COVID-19 pneumonia.

INTRODUCTION: The visual-well aerated lung (V-WAL) is a score for the visual quantification of the well aerated lung on CT scan in COVID-19 patients and its value at admission seems to predict future COVID-19 severity. The aim of the present study was to analyze the association between V-WAL and risk factors for severe COVID-19 evolution in people with multiple sclerosis. MATERIALS AND METHODS: This is an observational retrospective study, including people with multiple sclerosis and concomitant COVID-19, who were investigated with a lung CT scan at Hospital admission. The association of V-WAL with age, sex, EDSS, comorbidities, recent steroid use, and treatment (anti-CD20 vs other) was assessed by a multivariate linear regression model. RESULTS: In this observational retrospective study, the only factor that was significantly associated to a lower V-WAL at multivariable analysis was an increasing level of the EDSS (R2 = 0.41, p = 0.001), with an average decrease of 8% of V-WAL for each additional EDSS point. DISCUSSION AND CONCLUSION: This analysis shows that a high EDSS level is the main factor associated to the severity of lung involvement in a group of people with multiple sclerosis who were hospitalized for Covid-19.

Multiple Sclerosis Treatment in the COVID-19 Era: A Risk-Benefit Approach.

The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population.

"The Sword in the Stone": radical excision of deep infiltrating endometriosis with bowel shaving-a single-centre experience on 703 consecutive patients.

BACKGROUND: Laparoscopic segmental bowel resection, disc excision and rectal shaving are described as surgical options for the treatment of bowel endometriosis, but the gold standard has not yet established. The aim of the study is to investigate the efficacy of the laparoscopic bowel shaving technique in terms of pain symptomatology and to analyse early and late postoperative complications. METHODS: Retrospective cohort study of a series of 703 consecutive patients treated between January 2014 and December 2019 in a tertiary care referral centre. All patients underwent laparoscopic bowel shaving with concomitant radical excision of DIE. RESULTS: Bilateral posterolateral parametrectomy and ureterolysis were performed, respectively, in 314 (44.7%) and 318 cases (45.2%). A radical hysterectomy was performed in 107 cases (82.9%). Postoperative complications were infrequent: 17 patients required a reoperation (2.4%) and in this subgroup we registered 2 rectovaginal fistulas (0.3%), 4 patients received blood transfusion (0.6%), 12 patients (1.7%) experienced postoperative fever, 6 patients experienced impaired bladder voiding (0.9%) after 6 months. Median follow-up was 14 months. The study reported good clinical and surgical results, with a regression of symptoms (p < 0.0001) and an overall rate of recurrence of 6.5%. Clinical and instrumental criteria of bowel endometriosis relapse were exclusively detected in 5 patients (0.8%). Eleven patients (1.7%) with relapsed endometriosis were reoperated. CONCLUSIONS: Bowel shaving is a feasible and valuable surgical procedure. It is only the last step of a complex surgery which is aimed to minimize the residual quote of infiltrating nodule and requires a multidisciplinary team to achieve optimal treatment preoperatively, intraoperatively and postoperatively.

Role of ultrasonographic parameters for predicting tubal involvement in infertile patients affected by endometriosis: A retrospective cohort study.

INTRODUCTION: Transvaginal ultrasound is fundamental for the mapping of endometriosis, and the imaging criteria have been clearly described for different organs study. However, no specific ultrasonographic signs of tubal endometriosis have been reported, with the exception of hydrosalpinx, which is the expression of an extreme tubal damage and obstruction. The detection of tubal pathology in infertile patients is fundamental, therefore the aim of the study was to evaluate incidence of tubal endometriosis in infertile patients, and to analyze ultrasonographic signs useful for detection of this condition. MATERIAL AND METHODS: It is a single-center, retrospective cohort study. All 500 consecutive infertile women who underwent laparoscopic surgery for endometriosis were included. The preoperative workup included transvaginal ultrasound and was compared to intraoperative findings and histologic study. RESULTS: The incidence of tubal endometriosis in our study was 8%. Using hydrosalpinx as the ultrasonographic marker for tubal involvement the overall pooled, sensitivity and specificity of TVU were 12% (95%CI, 5-23%) and 99% (95%CI, 98-100%), respectively. If at least one ultrasonographic parameter like hydrosalpinx, periadnexal adhesions or ovarian cyst was considered as a sign of tubal endometriosis, a sensitivity, VPN and specificity were 94% (95% IC, 85-98%), 97% (95%IC, 93-99%) and 31% (95%CI, 27-36%), respectively. DISCUSSION: Hydrosalpinx as ultrasonographic sign alone is characterized by a high specificity but low sensitivity for detection of tubal endometriosis; its sensitivity can be improved by the addition of other markers such as endometrioma and/or periadnexal adhesions.

Total laparoscopic bladder resection in the management of deep endometriosis: "take it or leave it." Radicality versus persistence.

BACKGROUND: Bladder endometriosis (BE) is the most common external site of deep-infiltrating endometriosis (DIE) affecting the urinary tract. Frequently associated with other DIE lesions, it can be strongly related to a ventral spread of adenomyosis. Possible symptoms are urinary frequency, tenesmus and hematuria, and they are frequently related to DIE of the posterior and lateral compartment. Hormonal therapy can be used in non-symptomatic patients; conversely, in other cases surgical treatment is the management of choice. METHODS: Retrospective cohort study of a series of consecutive patients treated between September 2004 and December 2017 in a tertiary care referral center. Only full-thickness detrusor involvement was considered as BE. All patients underwent laparoscopic bladder resection with concomitant radical excision of DIE. RESULTS: BE was found in 264 patients and was associated with simultaneous bowel DIE requiring bowel resection in 140 patients (53%). Twenty-five patients (9.5%) had associated obstructive ureteral signs requiring ureteroneocystostomy. Mean hospital stay and time of catheter removal were 9.7 and 9.1 days, respectively. Postoperative major complications (< 28 days) were observed in 19 patients (7.2%). Follow-up was performed at 1, 6 and 12 months after surgery, with a 2.3% recurrence rate observed. CONCLUSIONS: Laparoscopic partial cystectomy for BE is a feasible and safe technique, and experienced laparoscopic surgeons should consider it the gold standard treatment. Surgical eradication leads to excellent surgical outcomes in terms of reduction of symptoms and recurrence rates, considering the need to maintain an adenomyotic uterus for fertility purposes.

Guillain-Barré-like axonal polyneuropathy associated with Toscana virus infection: A case report.

RATIONALE: Numerous cases of post-infectious Guillain-Barré syndrome (GBS) have been reported in the literature. Toscana virus (TOSV) is an arthropod-borne emerging pathogen in the Mediterranean area. PATIENT CONCERNS: A 40-year-old male patient was admitted to hospital for acute facial weakness, associated to numbness paraesthesias at lower and upper limbs. The neurological examination revealed facial diplegia and reduced tendon reflexes. The nerve conduction studies documented an acute motor and sensory axonal neuropathy (AMSAN); the lumbar puncture detected albuminocytologic dissociation. Serology for human immunodeficiency virus (HIV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), mumps, and Borrelia was negative, as was cerebrospinal fluid (CSF) polymerase chain reaction assay for Herpes virus, Borrelia, Mycoplasma pneumoniae, Cryptococcus, and Mycobacterium tubercolosis. Positivity for TOSV IgG antibodies was found on both CSF and serum; the patient remembered being recently exposed to mosquitoes. DIAGNOSES: The AMSAN subtype of GBS, subsequent to a TOSV infection, was diagnosed. INTERVENTIONS: The patient was treated with plasma-exchange with complete clinical recovery, but a relapse occurred 9 months later, when the nerve conduction studies confirmed the presence of an AMSAN, which benefited from oral steroids. OUTCOMES: A good clinical recovery was achieved after treatments. LESSONS: This is the first case, to the best of our knowledge, of a TOSV infection associated to a peripheral neuropathy mimicking a GBS syndrome, both clinically and electrophysiologically. The clinical spectrum of TOSV neurological complications seems to be wider than previously known: this should be taken into account by the scientific community and public health institutions.

Estimation of birthweight by measurement of fetal thigh soft-tissue thickness improves the detection of macrosomic fetuses.

The accuracy of sonographic estimation of birthweight in suspected macrosomic fetuses is compromised by the imprecision of the biometrical measurements. This prospective study evaluated the performance of an equation based on linear measurement of the soft tissue above the external side of the fetal femur. The performance of this algorithm was compared with two classical algorithms. Sonographic measurements were taken within 48 h before of delivery. Sixty-two patients with fetuses with suspected macrosomia were enrolled. The studied formulas were compared between them and showed a significant correlation with birthweight (p < 0.0001) and satisfactory statistical performances (r > 0.9). The new formula showed a reduced standard deviation that means a lower internal error in the prediction. This study supports the potential of this new approach for the estimation of birthweight in large fetuses based on sonographic linear measurements only.

Ulnar entrapment neuropathy in patients with type 2 diabetes mellitus: an electrodiagnostic study.

AIMS: This study aimed to assess the prevalence and electrophysiological features of ulnar entrapment neuropathy in patients with type 2 diabetes mellitus (DM). METHODS: Nerve conduction studies (NCS) were performed in a sample of consecutive diabetic patients aged 25-75 years, referred by the Diabetology Unit. NCS of the median, ulnar, radial, peroneal and sural nerves were performed on the non-dominant side. Median entrapment neuropathy at the wrist (MNW) and ulnar neuropathy at the elbow (UNE) and wrist (UNW) were diagnosed according to standard electrodiagnostic criteria. RESULTS: Sixty-four patients were enrolled, 28 male (44%), average age 61, average DM duration 14.5 years. Polyneuropathy was diagnosed in 45 subjects (70%). UNE was detected in 22 patients (34%) (4 did not have polyneuropathy), in the abductor digiti minimi in 16, the first interosseus in 14 and in both in 8. UNW was detected in 7 (11%) subjects and MNW in 40 (63%). NCS alterations consistent with ulnar neuropathy were detected in a high proportion of patients (45%), suggesting that the ulnar nerve is very susceptible to focal entrapment in DM. CONCLUSIONS: Upper limb sensory and motor NCS, including motor conduction velocity across the elbow, should be considered in the staging of DM patients.

Carcinosarcoma of the ovary: analysis of 13 cases and review of the literature.

OBJECTIVES: The aim of this study was to evaluate our experience with patients affected by ovarian carcinosarcoma. PATIENTS AND METHODS: During a 16-year period, data on 13 patients with ovarian carcinosarcoma were collected. They were obtained from hospital charts and follow-up visits. Survival curves were estimated by the Kaplan-Meier method and compared using the log-rank test. All tests were two-tailed with p values < 0.05 considered significant. RESULTS: Our study was conducted on 13 patients with ovarian carcinosarcoma referred to our unit, during an observation time of about 16 years (March 1994 to October 2010). An improved survival was observed in patients treated with optimal cytoreductive surgery with residual tumors <2 cm (30 vs. 5 months; p = 0.042). All patients underwent adjuvant chemotherapy based on the combination of cisplatin, epirubicin and ifosfamide (PEI) and taxol and carboplatin (TAX-CBDCA) regimen. Overall survival of the patient population was 17 months. CONCLUSIONS: Similarly to data published in the literature, we observed that malignant mixed mullerian ovarian tumors are very aggressive and are usually diagnosed at an advanced age and at an advanced stage of disease. Therefore, due to the rarity of the tumor we would like to add our series to those already published in the literature, although our treatment recommendations are actually based upon retrospective studies with a small patient population.