Risk Of Persistent Disease Research Articles

470. Relapsing COVID-19 Pneumonia in Patients Receiving Rituximab Therapy

BackgroundRituximab is a monoclonal antibody against the CD20 antigen on B-lymphocytes leading to B-cell death and depletion. Patients who receive rituximab and are infected with the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) causing coronavirus disease (COVID-19) may have increased difficultly clearing the virus and be at risk for persistent disease. While the limited literature available is mixed regarding the severity of COVID-19 in patients receiving rituximab, there is minimal literature regarding persistent and relapsing COVID-19 in this patient population. This is a case series of patients with persistent COVID-19 who previously received rituximab. MethodsThis is a retrospective review of 5 patients admitted between 1/1/2021 and 5/1/2021 to our institution with confirmed COVID-19 and receipt of rituximab for any indication within the previous 12 months. Information regarding hospital readmissions, time course of positive infection, medical management, disease severity, and discharge disposition were collected.ResultsFive patients, median age of 46, currently or recently on rituximab therapy were admitted a median of 2 times due to persistent, severe COVID-19 (Table 1). Patients received their initial COVID-19 diagnosis a median of 34 days (8-102 days) since their last rituximab administration and had documented SARS-CoV-2 infection a median of 66 days (19-195 days; Figure 1). All 5 patients received remdesivir and corticosteroids over the course of their COVID-19 disease and 2 patients received convalescent plasma therapy 1 and 5 days prior to a positive SARS-CoV-2 antibody IgG.Figure 1. Patient SARS-CoV-2 Infection Course Table 1. Patient Clinical and Therapeutic Data ConclusionRituximab therapy may be associated with persistent or relapsing COVID-19 disease. Controlled investigations are necessary to evaluate the exact impact anti-CD20 agents have on the course of COVID-19 and whether convalescent plasma or other therapies can prevent relapsing disease.Disclosures All Authors: No reported disclosures

Long-term outcome of differentiated thyroid cancer in children and young adults: risk stratification by ATA criteria and assessment of pre-ablation stimulated thyroglobulin as predictors of disease persistence.

Differentiated thyroid cancer (DTC) has an increasing incidence in childhood and adolescence but long-term outcome data are limited. We aimed to identify possible risk factors associated with disease persistence, with special focus on the usefulness of ATA risk stratification system and pre-ablation stimulated thyroglobulin (Tg) levels. We retrospectively studied 103 patients, 79 females (76.7%), aged 15.6 ± 3.2 years (range 5-21 years) who underwent total thyroidectomy for DTC. Patients were classified by ATA risk stratification criteria as low, intermediate, and high risk for recurrence. All, except five with papillary microcarcinoma, received radioactive iodine (RAI) treatment. At diagnosis, 44.7% of patients had cervical lymph node and 7.8% pulmonary metastases. Amongst the 72 patients with long-term follow-up data, 31.9% had persistent disease. Lymph node as well as pulmonary metastases and increased pre-ablation stimulated thyroglobulin (Tg) levels were associated with persistent disease. The risk of persistent disease was significantly higher in both the intermediate- (OR 17.95; 95% CI 2.66-120.94, p < 0.01) and high-risk (OR 17.65; 95% CI 4.47-69.74, p < 0.001) groups. ROC curve analysis showed that a pre-ablation Tg level higher than 14 ng/ml had a sensitivity of 94.7% to predict persistence, corresponding to a positive (PPV) and negative predictive values (NPV) of 66.7% and 93.8%, respectively. ATA risk stratification was validated in our population of children and young adults with DTC. Moreover, pre-ablation stimulated Tg levels of <14 ng/ml were associated with a low risk of long-term persistence and may therefore serve as a marker to identify patients who may need less intensive surveillance.

Use of Functional Magnetic Resonance Imaging in Cervical Cancer Patients With Incomplete Response on Positron Emission Tomography/Computed Tomography After Image-Based High-Dose-Rate Brachytherapy

Toinvestigate the correlation between positron emission tomography/computed tomography (PET/CT) response and outcome in the era of magnetic resonance imaging (MRI)-based planning and to assess whether the addition of diffusion-weighted MRI (DW-MRI) could more accurately classify treatment response and prognosis. A retrospective chart review identified 244 consecutive patients with International Federation of Gynecology and Obstetrics stage IB1-IVA cervical cancer treated with concurrent chemoradiation, including high-dose-rate image-based brachytherapy, between 2007 and 2016. Image-based brachytherapy was delivered with 5 intracavitary/interstitial fractions, each 5 to 6Gy per fraction. An complete response on posttreatment PET/CT (PET-CR) was discovered in 50 of 244 patients (20%) at a median interval of 3.3months (range, 2.1-7.7months) after treatment. After a median follow-up of 27months, 2-year overall survival was 83% in all patients. Metabolic response significantly impacted 2-year overall survival (94% complete response on posttreatment PET/CT vs 62.4% PET-IR, P<.001). Of those with a PET-IR, 16 of 50 patients (32%) suffered a local recurrence. A total of 27 of 50 patients with a PET-IR underwent DW-MRI; 11 of 27 posttreatment DW-MRI scans (40%) were interpreted as positive by central review (median apparent diffusion coefficient of 0.973×10-3mm2/s). Of the DW-MRI-positive patients, 9 of 11 (81.8%) suffered a histologically confirmed local recurrence, and 2 of 11 patients are without evidence of disease. Additionally, 16 of 27 DW-MRI studies were interpreted as negative, and 2 of 16 (12.5%) of these patients suffered a local recurrence. Diffusion-weighted MRI findings significantly impacted 2-year overall survival (83% negative DW-MRI vs 36% positive DW-MRI, P=.049). Incomplete PET/CT response was documented in 20% of patients after image-based brachytherapy for locally advanced cervical cancer. Integration of DW-MRI helped accurately identify patients at risk for persistent disease and worse long-term outcome. The value of DW-MRI requires further validation in a large prospective dataset as this modality may allow earlier evaluation and salvage treatment in those with PET-IR.

Adenotonsillectomy to treat obstructive sleep apnea: Is it enough?

Although adenotonsillectomy is the first line treatment for children with obstructive sleep apnea syndrome (0SAS),1 improvement in objectively documented outcomes is often inadequate and a substantial number of children have residual disease. Early recognition and treatment of children with persistent OSAS is required to prevent long-term morbidity. The management of these children is frequently complex and a multidisciplinary approach is required as most of them have additional risk factors for OSAS and comorbidities. In this paper, we first provide an overview of children at risk for persistent disease following adenotonsillectomy. Thereafter, we discuss different diagnostic modalities to evaluate the sites of persistent upper airway obstruction and the currently available treatment options. Pediatr Pulmonol. 2017;52:699-709. © 2016 Wiley Periodicals, Inc.

The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence.

ContextThere has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course.Materials and MethodsThis retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system.ResultsThe PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases).ConclusionsThe DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification.

Persistent and recurrent disease in patients with papillary thyroid carcinoma with clinically apparent (cN1), but not extensive, lymph node involvement and without other factors for poor prognosis.

Lymph node metastases (LNM) are frequent in patients with papillary thyroid cancer (PTC). The risk of persistent disease (PD) and tumor recurrence (TR) is increased when factors for poor prognosis other than LNM exist, when LNM are numerous, large, detected by preoperative ultrasonography (US), or exhibit extranodal extension. This study evaluated the risk of PD and TR in patients with LNM not exhibiting these characteristics. Eighty-six patients with 5 or fewer LNM detected during intraoperative inspection, but not by preoperative US, who had no other factors for poor prognosis [tumors > 4 cm, extensive extrathyroid invasion, vascular invasion, aggressive histological subtype, distant metastases, incomplete tumor resection], were studied. All patients underwent total thyroidectomy followed by radioiodine ablation. PD was defined as metastases on initial post-therapy whole-body scans (RxWBS) or detected by imaging methods up to 12 months after ablation. TR was defined as structural disease diagnosed more than one year after ablation in patients without PD. PD was diagnosed in 3/86 patients (3.5%). TR was observed in 2/83 patients (2.5%) after 62 months of follow-up. There was no case of death due to the disease. A correlation was observed between pre-ablation Tg and PD or TR [1/48 (2%) with Tg ≤ 2 ng/mL versus 2/22 (9%) with Tg > 2 ≤ 10 ng/mL versus 2/7 (28.5%) with Tg ≥ 10 ng/ml)]. It is noteworthy that 38 patients had up to 3 positive LN and pre-ablation Tg ≤ 2 ng/ml, and none of them had PD or TR. The frequency of PD and TR was low in patients with PTC with 5 or fewer LNM and without other factors for poor prognosis. Low postoperative stimulated Tg was predictive of the absence of PD and TR in these patients.

The Weight of the Resected Gland Predicts Rate of Success After Image-Guided Focused Parathyroidectomy.

A recent study of focused minimally invasive parathyroidectomy (FPTX) in sporadic primary hyperparathyroidism (pHPT) using intraoperative parathyroid hormone (ioPTH) measurements shows that inadequate ioPTH drop and multiglandular disease are more commonly found when a first gland<200 mg is resected. Our aim was to study if a resected gland that weighed <200 mg was associated with an increased persistence rate after FPTX. This is a cohort study of FPTX for pHPT performed in the period 1998-2013. FPTX was performed in patients with pHPT where Sestamibi and Ultrasound imaging localized single-gland disease, only one gland was excised and the weight recorded. IoPTH was not used routinely. Two groups were composed according to the weight of the resected gland: Group A<200 mg and Group B≥200 mg. Persistent or recurrent disease was defined if it occurred within, or after 6 months. The primary outcome measure was the rate of persisting pHPT. A total of 3,511 parathyroidectomies were performed, and a total 1,745 FPTX (1,347 female) met inclusion criteria. There were 245 and 1,500 patients in groups A and B, respectively. The rate of persistent pHPT was higher in Group A, 6.1 versus 2.0% (p<0.001). Findings at re-operative surgery showed that the ipsilateral gland was diseased in 47% (7/15) of persistent cases in group A. The risk of persistent disease after MIP was higher if the resected gland weighed ≤200 mg, and this corroborates the findings of a recent study. A heightened awareness of the possibility of multigland disease should be raised, and ioPTH monitoring, identification of the ipsilateral gland or bilateral exploration may be advisable in such cases.

Neck recurrence from thyroid carcinoma: serum thyroglobulin and high‐dose total body scan are not reliable criteria for cure after radioiodine treatment

Local and regional recurrences occur in up to 20% of patients with papillary and follicular thyroid carcinoma. Diagnostic work-up and treatment modalities are still controversial, because nodal control is difficult to ascertain. We assessed the value of serum thyroglobulin (Tg) determination and of high-dose 131I total body scan (TBS) for ascertaining the absence of disease in patients who had already been treated with radioiodine and who subsequently underwent surgery. Between 1990 and 2000, 105 patients who had been treated with radioiodine for lymph node recurrence with initial 131I uptake were included in a standardized protocol performed after withdrawal of thyroid hormone treatment: on day 1, serum Tg determination and administration of 3.7 GBq 131I; on day 4, 131I TBS; on day 5, surgery; on day 8, 131I TBS. In 25 patients the serum Tg obtained following thyroid hormone withdrawal was undetectable: for these patients, the 131I TBS showed uptake foci in 21 and pathology disclosed neoplastic foci in 19. In 32 patients the serum Tg ranged from 1 to 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 26 and pathology disclosed neoplastic foci in 28. In 48 patients the serum Tg level was above 10 ng/ml: for these patients, the 131I TBS showed uptake foci in 38 and pathology disclosed neoplastic foci in 46. Thus, no uptake was found preoperatively in 20 patients, among whom pathology disclosed lymph node metastases in 16. However, both tests were negative in only two of the 93 patients in whom pathology disclosed neoplastic foci. Serum Tg levels and 131I TBS cannot be considered as reliable indicators for the absence of disease in patients already treated with 131I. However, when both tests are negative, the risk of persistent disease is minimal.

Persistent disease after surgery for primary hyperparathyroidism: the long-term outcome.

Nineteen patients with persistent primary hyperparathyroidism were investigated to evaluate their clinical and laboratory status a long time after treatment was ended. The risk of persistent disease and need for extensive surgery for cure, i.e. more than two neck operations, or mediastinal exploration, was also evaluated. The medical records of 896 consecutive patients operated on for primary hyperparathyroidism were scrutinised at follow-up, a mean of 10.3 Years after surgery. Data on state of health, medication, bone fractures and other diagnoses were collected by use of a questionnaire. There were 600 patients still alive, among whom 13 had persistent disease and they were compared with 509 patients who were cured and without any suspicion of recurrent disease, according to laboratory examination. Serum calcium and creatinine values had with few exceptions remained stable over the Years. In five patients, serum calcium levels were within the normal range at follow-up. Still, all 19 patients were considered hyperparathyroid. They had substantial cardiovascular morbidity, and their state of health was not as good as that of the patients who were surgically cured. After one operation, 5.5% (95% confidence interval (CI) 4.0-7.2%) had persistent disease, and 2.1% after reoperation. Extensive surgery for cure was performed in 2% of the patients (95% CI 1.1-3.2%). We found that the state of health was significantly better for patients with cured primary hyperparathyroidism than for patients with persistent disease, but serious deterioration of laboratory values was uncommon. The result of the present study supports surgical treatment.

Villöse und nicht villöse gestationsbedingte Trophoblasterkrankungen - eine Übersicht

Gestationsbedingte Trophoblasterkrankungen (GTD) sind selten und stellen aufgrund ihrer klinikopathologischen Besonderheiten eine große Herausforderung für Pathologen und Kliniker dar. Die Blasenmole und die Partialmole als Formen der villösen GTD sind aufgrund ihres differenten Risikos für eine persistierende Erkrankung und ihres zytogenetischen Hintergrundes streng zu trennen. Die häufigste Form der nicht villösen GTD ist das Chorionkarzinom. Die notwendige Chemotherapie erfolgt in strenger Korrelation zum WHO-Prognosescore. Als weitere Entitäten sind in den vergangenen Jahren der Plazentabettknoten und die hyperplastische Implantationsstelle abgegrenzt worden, die keiner weiteren Therapie bedürfen und im Allgemeinen Zufallsbefunde darstellen. Zu den Tumoren, die vom intermediären Trophoblasten ausgehen, zählen der Plazentabetttumor und der jüngst beschriebene epitheloide Trophoblasttumor. Beide zeigen in der Majorität einen benignen Verlauf, sollten jedoch, ähnlich wie die Blasenmole und das Chorionkarzinom, mit sequenziellen HCG-Bestimmungen überwacht werden. Die Prognose der GTD hängt in entscheidendem Maße vom rechtzeitigen Beginn der adäquaten Therapie ab, was einer engen Kooperation zwischen Pathologen und Gynäkologen bedarf. Angestrebt werden sollte die Zentralisation der betroffenen Patientinnen in spezialisierten Einrichtungen.

Chronic recurrent multifocal osteomyelitis: Clinical outcomes after more than five years of follow-up

Objective: To determine the clinical outcomes of children with chronic recurrent multifocal osteomyelitis (CRMO). Study design: Inception cohorts of children with CRMO were established at two tertiary pediatric centers. Outcome data were obtained through review of hospital charts, interview and examination of patients, and completion of questionnaires by patients. Results: Of 45 eligible subjects, 23 (51%) were assessed. Median time since diagnosis was 13 years (range, 6-25). At evaluation, 6 (26%) had active disease; 18 (78%) had Health Assessment Questionnaire scores of 0 (no/minimal physical disability), and 5 had scores >0. Some impairment was seen in all domains of measurement of quality-of-life test, especially those concerning nonphysical aspects of health. Six (26%) subjects continued to have pain as a result of CRMO. Associated medical problems included arthritis in 6, sacroiliitis in 3, psoriasis in 5, recurrent pustular rashes in 2, and inflammatory bowel disease in 3. Conclusions: Long-term clinical outcomes for children with CRMO appear to be generally good, with most subjects having no evidence of disease activity or sequelae. However, a number of subjects had persistent disease and, therefore, remain at risk of physical and psychologic complications. Further research is required to identify patients at risk for persistent disease, and to determine therapies that may prevent morbidity. (J Pediatr 2002;141:198-203)

Flow Cytometric and Clinicopathologic Study of Complete Hydatidiform Moles with Special Reference to the Significance of Cytometric Aneuploidy

Objective. As complete hydatidiform moles (CMs) have been studied less with respect to aneuploidy and its clinical implications, the significance of cytometric aneuploidy in CMs was evaluated.Methods. Two hundred thirty-nine CMs were studied clinicopathologically and analyzed by flow cytometry using formalin-fixed paraffin-embedded tissues.Results. Of 239 CMs, 182 were diploid, 30 were tetraploid, and 27 were aneuploid (nontriploid/tetraploid aneuploid). There were no significant histologic differences among the diploid, tetraploid, and aneuploid CMs. Persistent disease developed in 20 of 114 CMs (17.6%) (16 of 77 diploid, 4 of 18 tetraploid, and none of 19 aneuploid CMs). Eight diploid and three tetraploid CMs were invasive, and one patient each with diploid CM and tetraploid CM developed choriocarcinoma and none of 19 patients with aneuploid CMs had sequelae.Conclusion. These results suggest that aneuploid CMs are associated with less risk for persistent disease than diploid or tetraploid CMs. DNA ploidy status may be an independent predictor of persistent disease.

Early partial hydatidiform mole: prevalence, histopathology, DNA ploidy, and persistence rate.

The widespread use of ultrasound in the diagnosis and management of intrauterine fetal death has resulted in moles being evacuated earlier than before. In order to clarify clinicopathologic features of early partial mole (PM), morphology and DNA ploidy of early (< or =12 gestational weeks) and late (>12 gestational weeks) partial PM were studied. A total of 80 early and 20 late PMs (37 from 1981-90; 63 from 1991-98) were analyzed. Mean gestational ages were 9.6 weeks for early PMs and 14.8 weeks for late PMs. Early PM was more common in 1991-1998 (57/63, 90%) than in 1981-1990 (23/37, 62%). Pre-evacuation diagnosis of hydatidiform mole was achieved in only 4 early and 1 late PMs. There were no significant differences in histology between early and late PMs, except that villi were smaller in early PMs and there was extensive stromal fibrosis in late PMs. Ploidy was as follows: 70 of 80 early PMs and 19 of 20 late PMs were triploid, 5 early PMs were aneuploid, and 5 early and 1 late PM were diploid. None of 45 patients with early PM and 1 of 11 with late triploid PM developed persistent gestational trophoblastic disease. Early PM is now more prevalent than it was previously. This may be a result of greater awareness of the entity of PM, its increased recognition by pathologists and the widespread use of ultrasound in the diagnosis and management of intrauterine fetal death. The diagnosis of PM should be based on pathological examination, since most PMs still elude clinical detection. DNA ploidy analysis is useful in the evaluation of problem cases. The risk of persistent disease seems to be very low in the case of early PMs.

A Randomized Clinical Trial of Cryotherapy, Laser Vaporization, and Loop Electrosurgical Excision for Treatment of Squamous Intraepithelial Lesions of the Cervix

In Brief Objective To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). Methods Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using χ2 statistics, logistic regression analysis, and the Cox proportional hazards model. Results Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6–37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). Conclusion The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above. Cryotherapy, laser vaporization, and loop electrosurgical excision are equally effective for treating squamous intraepithelial neoplasia of the cervix.

A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix

Objective: To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). Methods: Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using χ 2 statistics, logistic regression analysis, and the Cox proportional hazards model. Results: Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6–37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). Conclusion: The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above.