Median Duration Of Improvement Research Articles

Evaluation of the convalescent plasma therapy effectiveness and the factors that influence the therapeutic outcome in hospitalized COVID-19 patients: A retrospective cohort study.

Background: As an effective antiviral therapy is not available for the treatment of the current rapidly and continuously spreading coronavirus disease (COVID-19), it is very crucial to find an alternative treatment strategy. Convalescent plasma (CP) therapy has been used for prevention and treatment of many emerging infectious diseases, however, the results of current studies on CP in COVID-19 are not consistent. Therefore, this study aimed to evaluate the effectiveness of CP therapy in hospitalized patients with COVID-19, while evaluating patient and donor-related factors that might influence the therapeutic outcome. Methods: We conducted a retrospective cohort study on 312 patients with either severe or critical COVID-19, who were admitted to Al-Hakeem and Al-Amal hospitals in Al-Najaf city, Iraq from June to August 2020. The patients were allocated to either the plasma therapy group (152 patients) who received CP combined with standard therapy or the standard therapy group (160 patients). The outcome measures were the 21-day mortality rate and time to clinical improvement. Results: The overall cumulative survival rate was significantly higher in patients who received CP compared to standard therapy alone at 21 days (68.3% vs. 46.8%, p-value = 0.010), with mean survival at 17.6 vs. 15.3 days, (p-value = 0.010). In multivariate analysis, the plasma therapy effect was an independent predictor of survival (adjusted hazard ratio, 95% confidence interval: 0.368, 0.177 – 0.765). In terms of clinical improvement, the use of CP resulted in shorter clinical improvement (median duration of improvement: 8 vs. 11 days, p-value = 0.007), with 74.3% improvement rate after 21 days in CP compared to 65.0% in standard therapy. Conclusions: Therapy with CP in combination with standard therapy, independently improved survival in hospitalized patient with severe or critical COVID-19.

Phenol-Croton Oil Chemical Peeling Induces Durable Improvement of Constitutional Periorbital Dark Circles.

Constitutional periorbital dark circles (PDC) are common in skin of color and represent a therapeutic challenge. To summarize the experience of the International Peeling Society on the safety and effectiveness of deep chemical peeling in the treatment of constitutional PDC. Multi-institutional, retrospective case series (1990-2020) of constitutional PDC treated by deep chemical peeling. Descriptive analysis by age, sex, Fitzpatrick phototype, phenol-croton formula, degree and durability of improvement, and complications. Fifty-five phenol-croton oil peels were performed in 52 patients: 3 patients received a second peel for periorbital rhytids 72 to 84 months after the first peel. 92% (48/52) of patients were women; the median age was 46 years (range, 23-68 years). 89% (46/52) of patients were Fitzpatrick III-IV. Most common formula included phenol 60% to 65% and croton oil 0.6% to 0.7%. 89% (49/55) of peels demonstrated >50% clinical improvement. The median duration of improvement was 24 months (range, 1.5-168 months), and 69% (36/52) of patients demonstrated ongoing improvement at the last follow-up. 4% (2/55) of peels exhibited complications of persistent erythema that resolved without scarring. Based on its safety and effectiveness, deep chemical peels are a treatment of choice for constitutional PDC.

Radiation Therapy and Malignant Fistulae of Anorectal Cancers

Although fistulization is a well-studied late toxic effect of radiation therapy (RT), anorectal cancers (ARCs) can present with malignant fistulae (MF) and negatively affect quality of life. The effect of RT, often combined with concurrent chemotherapy, on MF needs systematic analysis, because practitioners are concerned that RT may exacerbate MF. We reviewed our institutional series evaluating the hypothesis that RT worsens MF. A single-institutional retrospective analysis of patients with ARC receiving RT from 2006 to 2019 was performed. These patients were screened for MF. Any MF resected before RT and RT not directed at the site of MF were excluded. Effects were assessed by review of available follow-up documentation and imaging. A total of 639 patients with ARC were reviewed, and 47 had MF (7.4%). With a median follow-up of 22 months (range, 2-133 months), RT improved MF in 17 of 29 evaluable patients (59%), with 9 of 29 (31.0%) having resolution. The median time to improvement was 50 days (range, 25-117 days); the median duration of improvement was 161 days (range, 0-1941 days). Malignant fistulae persisted in 12 of 29 patients (41%), with persistent local disease in all cases; in 2 cases, MF worsened concomitant with local progression. In all, 7.4% of patients with ARC presented with MF. Radiation therapy led to improvement or resolution in more than half of evaluable patients. Persistence or worsening of MF was only observed in patients with refractory or progressive local disease. Based on our findings, MF is not a contraindication to RT and may be considered as an independent indication for palliative RT.

Symptom burden and quality of life with chemotherapy for recurrent ovarian cancer: the Gynecologic Cancer InterGroup-Symptom Benefit Study

ObjectiveThe Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory...

771P - PALAESTRA: A phase II trial with short-course radiotherapy followed by chemotherapy as palliative treatment in esophageal adenocarcinoma

Abstract Background Patients with esophageal cancer commonly suffer from dysphagia, leading to nutritional problems and impaired quality of life. Self-expanding metallic stents (SEMS) is frequently used in the palliative setting providing a rapid but short-term relief. In this phase II study we assessed a novel first-line treatment schedule with short-course radiotherapy followed by chemotherapy with the primary aim to achieve a long-term improvement of dysphagia. Methods Patients with dysphagia due to adenocarcinoma of the esophagus or esophagogastric junction, not eligible for curative treatment, were recruited. Treatment consisted of radiotherapy (5 x 4 Gy) followed by 4 cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a 5-grade scale and a response was defined as an improvement from baseline with at least one step in dysphagia score during the study treatment period or within 4 weeks after end of study treatment. Response of the primary tumour was assessed using endoscopy and PET imaging. Results From October 2014 to May 2018 a total of 29 patients were enrolled. Median age was 68 years. WHO PS (0/1/2); 10/12/7, female/male; 6/23, stage III/IV; 3/26, dysphagia score (0/1/2/3/4); 0/15/6/7/1. In the per-protocol (PP) population of 23 patients (treated with at least 4 fractions of radiotherapy and 2 cycles of chemotherapy) the rate of dysphagia improvement was 91%, the median time to improvement was 2.0 months (95% CI: 1.5, 2.5) and the median duration of improvement was 12.2 months (95% CI: 6.2, 18.2). 5 patients received SEMS during follow-up. In the PP population the endoscopic response rate was 78% with 22% complete responders, the metabolic response rate of the primary tumor was 61% with 30% complete responders. Median overall survival was 16.0 months (95% CI: 9.6, 22.5). In the safety population (28 patients who started treatment) the most frequent grade 3-4 adverse events were neutropenia (32%), infection (25%), pain (14%), esophagitis (11%) and anorexia (11%). Conclusions Palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma. Clinical trial identification 2014-002362-74. Legal entity responsible for the study Skane University Hospital, Department of Oncology. Funding Lund University Faculty of Medicine and Skane University Hospital Funds and Donations. Disclosure All authors have declared no conflicts of interest.

Palliative short-course hypofractionated radiotherapy followed by chemotherapy in esophageal adenocarcinoma: the phase II PALAESTRA trial

Background: The majority of patients with incurable esophageal adenocarcinoma suffer from dysphagia. We assessed a novel treatment strategy with initial short-course radiotherapy followed by chemotherapy with the primary aim to achieve long-term relief of dysphagia.Methods: This phase II trial included treatment-naîve patients with dysphagia due to esophageal adenocarcinoma not eligible for curative treatment. External beam radiotherapy with 20 Gy in five fractions to the primary tumor was followed by four cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a five-grade scale.Results: From October 2014 to May 2018 a total of 29 patients were enrolled. The rate of dysphagia improvement was 79%, median duration of improvement 6.7 months (12.2 months for responders) and median overall survival 9.9 months. In the pre-specified per protocol analysis (23 patients) the rate of dysphagia improvement was 91%, median duration of improvement 12.2 months (14.0 months for responders) and median overall survival 16.0 months. The most common grade 3–4 adverse events were neutropenia (29%), infection (25%), anorexia (11%), esophagitis (11%) and fatigue (11%).Conclusion: Initial palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma.

Hydrodistension plus Onabotulinumtoxin A in bladder pain syndrome refractory to conservative treatments

Abstract Introduction For bladder pain syndrome (BPS) refractory to conservative treatment, the European guidelines consider bladder hydrodistention (HD) under anesthesia and the injection of Onabotulinumtoxin A (OnabotA) jointly. The objective of this study was to assess our experience in implementing this technique. Material and methods A prospective study of 25 patients with BPS who underwent HD plus a submucosal injection of 100 U of OnabotA in trigone. The Hunner lesions were treated endoscopically using resection or electrocoagulation. Thirty-eight procedures were performed (25 first interventions and 13 reoperations). To study the clinical change, we evaluated the subjective improvement (Treatment Benefit Scale [TBS] and Patient Global Impression of Change [PGIC] scales), the visual analog scale (VAS) for pain, the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) questionnaire and the voiding diary for 3 days. For the data analysis, we employed the Wilcoxon, Kruskal–Wallis, Kaplan–Meier and log-rank tests. Results We observed subjective improvement in 21 patients (84%), which was significant in 47% of these patients, moderate in 41.2% and slight in 11.8%. Four patients did not improve. A post-treatment reduction in the pain VAS (from 7.1 to 1.8 points; p = .001), in daytime (from 11.8 to 7.5; p = .012) and night-time (from 5.9 to 3.6; p = .003) voiding frequency and in the BPIC-SS (from 27.9 to 11.2 points; p = .042). The degree of improvement was not related to age, the presence of bladder lesions or the treatment of relapses. The median duration of improvement was 7 months (95% CI: 5.69–8.31), although this duration was somewhat longer for the patients younger than 65 years. Mild complications occurred in 23.7% of the cases. Conclusions The joint implementation of HD plus OnabotA is a valid therapeutic option in refractory BPS, which provides good clinical results and maintains its effectiveness in retreatments.

Hidrodistensión bajo anestesia más inyección de Onabotulinumtoxin A en pacientes con síndrome de dolor vesical refractario a tratamiento conservador

For bladder pain syndrome (BPS) refractory to conservative treatment, the European guidelines consider bladder hydrodistention (HD) under anaesthesia and the injection of Onabotulinumtoxin A (OnabotA) jointly. The objective of this study was to assess our experience in implementing this technique. A prospective study of 25 patients with BPS who underwent HD plus a submucosal injection of 100 U of OnabotA in trigone. The Hunner lesions were treated endoscopically using resection or electrocoagulation. Thirty-eight procedures were performed (25 first interventions and 13 reoperations). To study the clinical change, we evaluated the subjective improvement (Treatment Benefit Scale [TBS] and Patient Global Impression of Change [PGIC] scales), the visual analogue scale (VAS) for pain, the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) questionnaire and the voiding diary for 3 days. For the data analysis, we employed the Wilcoxon, Kruskal-Wallis, Kaplan-Meier and log-rank tests. We observed subjective improvement in 21 patients (84%), which was significant in 47% of these patients, moderate in 41.2% and slight in 11.8%. Four patients did not improve. A post-treatment reduction in the pain VAS (from 7.1 to 1.8 points; P=.001), in daytime (from 11.8 to 7.5; P=.012) and night-time (from 5.9 to 3.6; P=.003) voiding frequency and in the BPIC-SS (from 27.9 to 11.2 points; P=.042). The degree of improvement was not related to age, the presence of bladder lesions or the treatment of relapses. The median duration of improvement was 7 months (95% CI 5.69-8.31), although this duration was somewhat longer for the patients younger than 65 years. Mild complications occurred in 23.7% of the cases. The joint implementation of HD plus OnabotA is a valid therapeutic option in refractory BPS, which provides good clinical results and maintains its effectiveness in retreatments.

Hematological Improvement in AML/RAEB Elderly Patients Treated with Valproic Acid and Low-Dose ARA-C

Abstract Histone deacetilase inhibitors (HDCAi) have been shown to modulate gene expression with pro-differentiative effects. Valproic acid (VPA) has HDCAi activity and synergizes with Ara-C to differentiate AML blasts in vitro. VPA is orally applicable and has a low toxicity prophile. We tried to assess the therapeutic activity of VPA in combination with low-dose Ara-C in elderly/frail AML/RAEB patients. We enrolled in this study 31 patients with Myeloid Pathologies. Fifteen pts had diagnosis of oligoblastic AML (M0:2, M1: 7, M2: 1, M4:1, M5: 4); 13 patients had RAEB (RAEB 1: 2, RAEB 2: 11) with the following IPSS: int-1=2, int-2= 2, high= 6. Three other patients had progression from previous MPS (1 from ET, 2 from LMMC). Median age was 70 yrs (range: 53 to 84). Median time from Diagnosis to treatment was 15 months (range 1 to 79). Clinical status at start of protocol was: at Diagnosis = 13 pts, Resistant after induction =6 pts, Relapsed after CR =11 pts, Relapsed after allogeneic transplant =1 pt). All patients were excluded from conventional chemotherapy for age and multiple comorbidities. In 27 out of 31, these comorbidities required therapy or periodic controls (grade 3), other 2 pts had one of G4 grade (life-threatening). Thirteen patients were defined “frail” because they presented 3 of G3 comorbidities or at least a G4 one. Twenty-nine pts were evaluated for autosufficiency with ADL score, 5 of them didn’t reach the score of 6, showing impairment in their autosufficiency. Assessing functional autonomy, IADL score showed deficiency in 17 of 29 patients. In our protocol, VPA was administered in continuum to reach serum concentration of 50–100μg/ml. Ara-C was given in cycles of 8 days, 40 mg/day. Ammonium and valproic acid serum level was routinely checked. Bone marrow examination was done at the enrollement in the study, after sixth cycle of Ara-C and/or if improvement of blood counts were observed. In two patients that were in CR at the end of sixth cycle, VPA was maintained; other six cycles of Ara-C were given monthly and thereafter every third month until relapse. Six patients received the treatment for at least 6 cycles, the other patients had a median of 2 cycles, (range 1 to 4). Ten patients are still in treatment, 17 dropped out for progression/death, one patient underwent reduced intensity allotransplant while in remission. From the start of protocol, median overall survival was 4 mths, range 1 to 33 mths. Fifteen pts are alive now. Overall, 11 of 31 patients (35%) had hematological improvement (according to IWG, 2008), including 7 CR (22%) with clearing of blasts in the marrow and normalization of blood counts. The median cycle of improvement was 2 (range 1 to 4) and the median duration of improvement was 2 months (range 1 to 23 months), including two pts that lasted in CR for 10 and 23 months; 3 pts are still in CR at 5,8 and 10 mths from the starting of response, one patient is in Hematological Improvenment at 2 mths. Hematological toxicity requiring platelet transfusion was seen in 17 patients, while 10 pts required red cell transfusion. Transient hyperammoniemia was seen in one patient; liver toxicity in another patient. Neutropenia-related infections were seen in 3 pts. Adding VPA to low-dose Ara-C, some complete responses and some improvements in peripheral cytopenias can be achieved without a significant increase in toxicity. Therefore this therapeutic protocol is feasible for elderly/frail oligoblastic AML/RAEB patients who cannot have aggressive therapy.

Short-Course Versus Split-Course Radiotherapy in Metastatic Spinal Cord Compression: Results of a Phase III, Randomized, Multicenter Trial

Hypofractionated radiotherapy (RT) is often used in the treatment of metastatic spinal cord compression (MSCC). This randomized trial was planned to assess the clinical outcome and toxicity of two different hypofractionated RT regimens in MSCC. Three hundred patients with MSCC were randomly assigned to a short-course RT (8 Gy x 2 days) or to a split-course RT (5 Gy x 3; 3 Gy x 5). Only patients with a short life expectancy entered the protocol. Median follow-up was 33 months (range, 4 to 61 months). A total of 276 (92%) patients were assessable; 142 (51%) treated with the short-course and 134 (49%) treated with the split-course RT regimen. There was no significant difference in response, duration of response, survival, or toxicity found between the two arms. When short- versus split-course regimens were compared, after RT 56% and 59% patients had back pain relief, 68% and 71% were able to walk, and 90% and 89% had good bladder function, respectively. Median survival was 4 months and median duration of improvement was 3.5 months for both arms. Toxicity was equally distributed between the two arms: grade 3 esophagitis or pharyngitis was registered in four patients (1.5%), grade 3 diarrhea occurred in four patients (1.5%), and grade 3 vomiting or nausea occurred in 10 patients (6%). Late toxicity was never recorded. Both hypofractionated RT schedules adopted were effective and had acceptable toxicity. However, considering the advantages of the short-course regimen in terms of patient convenience and machine time, it could become the RT regimen of choice in the clinical practice for MSCC patients.

Hydrocephalus in radiation leukoencephalopathy: results of ventriculoperitoneal shunting.

To assess the clinical benefit of ventriculoperitoneal shunting in patients suffering from radiotherapy-induced leukoencephalopathy. Retrospective review of a single institutional experience. Thirty-one patients with the postradiotherapy syndrome received ventriculoperitoneal shunts. All had a history of cranial irradiation, progressive ventriculomegaly visible on neuroimaging scans, and neurologic decline; other causes of hydrocephalus were excluded. All 31 patients had cognitive deficits: 30 had gait disturbance and 24 were incontinent. Twenty-four (80%) of 30 assessable patients achieved symptomatic improvement an average of 1.6 months after ventriculoperitoneal shunting. Incontinence and gait problems were more likely to improve than cognition. Sixteen (53%) of 30 patients achieved a good overall functional outcome, and incontinence was the only feature significantly associated with good outcome (P=.04). Neither cerebrospinal fluid-opening pressure nor tap tests predicted improvement from ventriculoperitoneal shunting. Median duration of improvement was 6 months, and median survival after receiving the shunt was 14.5 months. Shunt-related complications occurred in 10 (33%) of 30 patients, with 1 fatal outcome. Our results from ventriculoperitoneal shunting in selected patients with radiation-induced hydrocephalus suggest potential benefit. Improvement is incomplete and temporary, but can improve quality of life. Reliable predictors of successful shunt outcome were not identified.

Achalasia of the oesophagus in elderly patients responds poorly to conservative therapy.

In a retrospective study the symptoms and results of pneumatic dilatation in achalasia of the oesophagus were analysed in 11 patients (six women) aged 65 years and above (group 1) and compared with 19 younger patients (two women, group 2) over a 48-month period. Weight loss occurred in 91% of group 1 patients and 53% of group 2 patients. Pulmonary complications were commoner in group 1 than in group 2. All patients in group 1 and 84% of patients in group 2 complained of regurgitation. Lower oesophageal sphincter pressures were similar in the groups but the median diameter of the oesophageal body was greater in group 1 patients. The duration of dysphagia before presentation was longer in group 1 (median 5 years; range 1-9 years) compared with group 2 (median 2 years; range 0.5-4 years). None of the six elderly patients receiving pharmacological treatment with nifedipine or nitrates improved while five of the six younger patients treated with medications reported transient improvement. In group 1 only 50% of the pneumatic dilatations resulted in improvement and the median duration of improvement was 12 weeks. These results were significantly worse than those in group 2 where 90% of the dilatations resulted in improvement which lasted for a median duration of 52 weeks. Long-term results were satisfactory in six of the 11 elderly patients and 16 of the 19 younger patients.

Radiation therapy in metastatic spinal cord compression. A prospective analysis of 105 consecutive patients

One hundred thirty consecutive patients with metastatic spinal cord compression (MSCC) were entered in a therapeutic protocol in which radiation therapy (RT) played the main role. When MSCC is diagnosed by clinical-radiologic methods such as myelography with or without computed tomography (CT) or magnetic resonance imaging (MRI), steroids are given and RT treatment started within 24 hours. When diagnostic doubts exist or stabilization is necessary, surgery precedes RT. Chemohormonal potentially responsive tumors are also treated with chemotherapy or hormonal therapy. Twelve patients (9.2%) underwent surgery plus RT, and 118 (90.8%) received RT alone. Thirteen (11%) early death patients were not evaluable. The 105 evaluable cases that received RT alone were analyzed. Median follow-up was 15 months (range, 4 to 38 months). Response among patients with back pain was 80%. In cases with motor dysfunction, 48.6% improved, and in 33 of 105 patients (31.4%) without motor disability there was no deterioration. Forty percent of patients with autonomic dysfunction responded to RT. Median survival time was 7 months with a 36% probability of survival for 1 year. The median duration of improvement was 8 months. The most important prognostic factor was early diagnosis. Radiosensitivity of tumor was only important in paraparetic patients in predicting response to RT. Complete myelographic block significantly diminished response to RT. Vertebral collapse did not influence response or survival.

Non-small cell lung cancer. Neuroresection of the solitary intracranial metastasis followed by radiochemotherapy.

Fifteen selected patients with advanced intrathoracic non-small cell lung cancer and solitary metastasis were treated by a combined program including craniotomy, brain and chest irradiation, and systemic chemotherapy. One patient died because of cerebral hemorrhage after the operation. Five patients failed to achieve neurologic benefit. Nine patients improved their neurologic grading, and the median duration of improvement was 10 months (range, 1-26 months). The responses to systemic treatment were: one complete response, three partial responses, six stable disease responses, and four progressive disease responses. The overall median survival was 6 months from craniotomy and 12 months from diagnosis. Five patients became long survivors; they had a survival time ranging between 12 and 26 months after craniotomy. In conclusion, one third of patients had a satisfactory response to treatment; this outlines the value of the combined aggressive therapeutic approach also performed in patients who had a highly unfavorable prognoses.

Surgical treatment of idiopathic hydrocephalus in elderly patients.

We studied 45 adult patients with idiopathic hydrocephalus who had undergone a shunting procedure at the Mayo Clinic during a 16-year period. The follow-up period extended up to 157 months. Thirty-four of the 45 patients (75%) improved at some time after the operation, and 19 (42%) experienced continuous improvement. The median duration of improvement was 24 months. Patients who had symptoms for less than 2 years were most likely to improve. CT played an important role in the diagnosis and follow-up, but ventricular size or degree of atrophy did not correlate with response.

Cryoanalgesia for intractable perineal pain.

Cryoanalgesia, the local application of extreme cold to nerves to produce analgesia, has been used to treat patients with intractable perineal pain. The cryoprobe was inserted percutaneously through the sacral hiatus into the sacral canal to produce anaesthesia of the lower sacral nerve roots. Forty patients received a total of 70 treatments: 31 patients (78%) were helped by the procedure and the median duration of improvement was 30 days. The treatment was more successful in relieving symptoms in patients suffering from pelvic cancer and coccydynia. The best results were obtained in those patients who received numerous freeze applications or prolonged freezing.