Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Patient preferences of chemotherapy treatment options and tolerance of chemotherapy side effects in advanced stage lung cancer.

BACKGROUND: In the U.S., lung cancer accounts for 14% of cancer diagnoses and 28% of cancer deaths annually. Since no cure exists for advanced lung cancer, the main treatment goal is to prolong survival. Chemotherapy regimens produce side effects with different profiles. Coupling this with individual patient's preferred side effects could result in patient-centered choices leading to better treatment outcomes. There are apparently no previous studies of or tools for assessing and utilizing patient chemotherapy preferences in clinical settings. The long-term goal of the study was to facilitate patients' treatment choices for advanced-stage lung cancer. A primary aim was to determine how preferences for chemotherapy side effects relate to chemotherapy choices. METHODS: An observational, longitudinal, open cohort study of patients with advanced-stage non-small cell lung cancer (NSCLC) was conducted. Data sources included patient medical records and from one to three interviews per subject. Data were analyzed using Chi-square, Fisher's Exact and McNamara's test, and logistic regression. RESULTS: Patients identified the top three chemotherapy side effects that they would most like to avoid: shortness of breath, bleeding, and fatigue. These side effects were similar between first and last interviews, although the rank order changed after patients experienced chemotherapy. CONCLUSIONS: Patients ranked drug side effects that they would most like to avoid. Patient-centered clinical care and patient-centered outcomes research are feasible and may be enhanced by stakeholder commitment. The study results are limited to patients with advanced NSCLC. Most of the subjects were White, since patients were drawn from the U.S. Midwest, a predominantly White population.

Hereditary angioedema with C1 inhibitor (C1-INH) deficit: the strength of recognition (51 cases).

Hereditary angioedema (HAE) is a rare autosomal dominant disease due to C1 esterase inhibitor deficiency (C1-INH). The disease is characterized by subcutaneous and submucosal edema in the absence of urticaria due to the accumulation of bradykinin. This descriptive study aimed to evaluate the clinical characteristics of patients with a confirmed diagnosis of HAE referred to our Outpatient Clinic between December 2009 and November 2017. Fifty-one patients (38 F, 13 M) with a mean age of 32 years (range: 7-70 y) were included. Family history of HAE was reported in 70% (36/51) of the cases; 33/46 patients became symptomatic by 18 years of age. The median time between onset of symptoms and diagnosis was 13 years (3 mo-50 y). The most frequent triggering factors for attacks were stress (74.4%), trauma (56.4%), and hormonal variations (56%). The main symptoms were subcutaneous edema in 93.5% (43/46) of patients, gastrointestinal symptoms in 84.8% (39/46), and obstruction in the upper airways in 34.8% (16/46). Hospitalization occurred in 65.2%, of whom 13.3% had to be transferred to the Intensive Care Unit. Prophylactic treatment was instituted in 87% (40/46) of patients, and 56.5% (26/46) required additional treatment to control attacks. Owing to our data collection over a period of 8 years, a significant number of patients were identified by this HAE reference center. Despite early recognition and prophylactic treatment, a high percentage of patients were hospitalized. HAE is still diagnosed late, reinforcing the need for more reference centers specialized in diagnosis and educational projects for health professionals.

Changes in the physiochemical, microbial, and sensory characteristics of fresh pork sausage containing rosemary and green tea extracts during retail display.

The effects of adding combinations of rosemary (R: 1500, 2000, 2500 ppm) and green tea (G: 100, 200, 300 ppm) extracts in combination with synthetic antioxidants on the physiochemical, microbial, and sensory characteristics of fresh pork sausage were evaluated. R and G improved (P < .05) oxidative stability as evidenced by lower TBARS. R2500 and G300 had fewer PPC than the control at d 7, 14, and 21 of storage. Consumer acceptability scores were greater (P < .05) in sausages with R and G when compared to the control, and the majority of the R and G treatments were liked by 98% of the respondents. Treatment combinations of at least R2000 and G200 were described by positive drivers of liking such as spice-complex, ginger, nutmeg, rosemary flavors and aromas and lower scores for descriptors such as rancid, fruity, and off-flavor/odor. This research demonstrates that rosemary and green tea extracts improved the keeping quality of fresh pork sausage under simulated retail display.

Hereditary angioedema with C1 inhibitor (C1-INH) deficit: the strength of recognition (51 cases)

Hereditary angioedema (HAE) is a rare autosomal dominant disease due to C1 esterase inhibitor deficiency (C1-INH). The disease is characterized by subcutaneous and submucosal edema in the absence of urticaria due to the accumulation of bradykinin. This descriptive study aimed to evaluate the clinical characteristics of patients with a confirmed diagnosis of HAE referred to our Outpatient Clinic between December 2009 and November 2017. Fifty-one patients (38 F, 13 M) with a mean age of 32 years (range: 7-70 y) were included. Family history of HAE was reported in 70% (36/51) of the cases; 33/46 patients became symptomatic by 18 years of age. The median time between onset of symptoms and diagnosis was 13 years (3 mo-50 y). The most frequent triggering factors for attacks were stress (74.4%), trauma (56.4%), and hormonal variations (56%). The main symptoms were subcutaneous edema in 93.5% (43/46) of patients, gastrointestinal symptoms in 84.8% (39/46), and obstruction in the upper airways in 34.8% (16/46). Hospitalization occurred in 65.2%, of whom 13.3% had to be transferred to the Intensive Care Unit. Prophylactic treatment was instituted in 87% (40/46) of patients, and 56.5% (26/46) required additional treatment to control attacks. Owing to our data collection over a period of 8 years, a significant number of patients were identified by this HAE reference center. Despite early recognition and prophylactic treatment, a high percentage of patients were hospitalized. HAE is still diagnosed late, reinforcing the need for more reference centers specialized in diagnosis and educational projects for health professionals.

The evolution of the medical workforce in Cape Verde since independence in 1975.

BACKGROUND: Cape Verdean doctors have always graduated abroad. The first experience of pre-graduate medical education in Cape Verde begun in October 2015. Counting how many doctors Cape Verde has, knowing who they are, and knowing how they are distributed are very important to help fine-tune the medical training. The aim of this study is to analyze the evolution of the medical workforce in Cape Verde to support medical education implementation. METHODS: Secondary data on doctors, from July 1975 until December 2014, collected from the Ministry of Health, were entered into an SPSS 20 database and studied by a simple descriptive statistical analysis. RESULTS: The database included data on 401 medical doctors. There was a predominance of females (n = 218; 54.4%). The overwhelming majority (n = 378; 94.3%) graduated from 5 of the 17 countries that contributed to the training of Cape Verdean doctors. All the islands of this archipelago country contributed to the 324 (80.8%) doctors born in the country. Of the 272 doctors still active in December 2014, 119 (43.6%) were general practitioners and 153 (56.4%) had specialized in one of the 31 specialties. The national ratio of doctors per 10 000 inhabitants was 5.25, but the reality varied significantly among islands. About one third of the doctors (n = 86; 32%) were at the primary care level, 38 (14%) at the secondary care level, and 144 (52%) in central hospitals. In 2053, all active physicians in 2014 will already be retired. CONCLUSIONS: This is a unique study of the evolution of the medical workforce of a country over 40 years, from the first day of independence. The study illustrates the importance of international collaborations, particularly of Cuba, in sustaining the medical workforce in Cape Verde. It is an example of how this collaboration was used to equip the country with doctors in an increasingly more equitable distribution across all islands. The study further illustrates the progressive feminization of the medical workforce. The study clarifies the effort required from the emerging medical faculty to supply the national health system with the needed number of doctors.

Resultados de la colecistectomía videolaparoscópica en el adulto mayor / Analysis of laparoscopic cholecystectomy in the elderly

Se presenta la experiencia en el tratamiento quirúrgico de la patología vesicular litiásica, mediante videolaparoscopia, en una serie prospectiva de 119 pacientes de 60 o más años de edad, de ambos sexos, operados entre Marzo de 2003 y Marzo de 2004, en el Departamento y Servicio de Cirugía del Hospital Barros Luco Trudeau analizando la patología médica asociada, presente en el 70 por ciento, los hallazgos relevantes del estudio ecotomográfico preoperatorio (99,1 por ciento), las cifras de conversión a cirugía laparotómica (19 por ciento), la morbilidad (8,4 por ciento) y la mortalidad (0 por ciento).

We report our surgical experience in videolaparoscopic cholecystectomy in 119 patients with 60 or more years old, operated between March 2003 and March 2004, at the Barros Luco's Surgical Department and Service. We analized the medical pathology (70 percent of patients); the relevant finding at the preoperative ultrasonic study (99,2 percent of patients); the conversion rate (19 percent) and postoperatory results.

A clinico-pathologic study of peptic ulcer in a chronic disease hospital: I the incidence of fatality and its complications

1. The autopsy incidence of chronic peptic ulcer in 3123 consecutive autopsies in a chronic disease hospital is 3.5 per cent. The autopsy incidence for patients 60 years or older is 4.0 per cent. There is no remarkable sex incidence among the patients of this chronic disease hospital. The ulcers tend to be large, the average size being 2.0 centimeters2. The diagnosis of peptic ulcer in this particular series of 110 patients was often missed because of the paucity of ulcer symptoms, incomplete work-up and inability to demonstrate the lesion by x-ray in a great number of cases. There were 77 undiagnosed cases, 53 having no record of abdominal pain. GI series was done in 41 patients, the peptic ulcer being demonstrated in only 27 instances (65.9%). No GI series was done in 15 patients who had complained of abdominal pain; the ulcer would probably have been seen by x-ray in at least 10 of these 15 patients3. The incidence and fatality of complications, specifically gastro-intestinal hemorrhage and acute perforation, are remarkably high in this study. Hemorrhage occurred in 47.3 per cent and acute perforation in 11.8 per cent of our cases. Forty-eight of our 110 patients (43.6%) died as a result of the complication, namely, hemorrhage in 32.7 per cent and acute perforation with generalized peritonitis in 10.9 per cent. There were only 4 cases of pyloric obstruction requiring a by-pass operation. There was only one instance of malignant transformation of a benign ulcer. The three largest ulcers (all gastric) measuring 6.0, 7.5, and 8.0 centimeters respectively were all benign4. Peptic ulcer in aged patients suffering from other serious diseases is a diagnostic and therapeutic problem. However, with more awareness on the part of the attending physician that vague abdominal discomfort may signify an underlying peptic ulcer, diagnosis will be made more often. With better accuracy in diagnosis, therapy will be less problematical since it can be instituted before complications supervene. Although the operative mortality in elderly patients is comparatively high, a liberal use of surgical treatment of peptic ulcer in this group of patient is justified for two reasons, namely, (1) the disease often proves resistant to the medical regimen, and (2) there is a much higher incidence and mortality of complications in the non-surgically treated cases. (Summary)

Reduction in tuberculin skin-test conversion rate after improved adherence to tuberculosis isolation.

The rate of purified protein derivative (PPD) conversion in workers at our hospital increased to 1.7% in 1991. After implementation of mandatory respiratory isolation of patients with community-acquired pneumonia, the rate dropped to 0.6%. This policy may protect workers in institutions where the majority of patients with pneumonia have risk factors for tuberculosis.

Outbreak of cryptosporidiosis in dairy goats in Brazil.

An outbreak of cryptosporidiosis is reported among 22 suckling kids aged one to two weeks which were maintained for experimental purposes at the veterinary hospital of the University of Minas Gerais. They were divided into three groups. Group A consisted of 10 animals with acute diarrhoea; initially their faeces were pasty but later they were excreted in watery streams. The animals were treated with gentamicin and fluid therapy but did not respond to treatment and died within a week. Postmortem examination revealed liquid intestinal contents, enlarged mesenteric lymph nodes, and hyperaemia and haemorrhage were observed in the final third of the small intestine of some of the animals. Of the 10 animals in group B four had diarrhoea and six were normal; postmortem examination showed that the macroscopic changes were similar to those observed in group A. Three of the animals with diarrhoea had a massive Cryptosporidium infection in the final third of the small intestine, caecum and colon. Four of the six normal animals had a moderate Cryptosporidium infection in the same organs. The two kids in group C died; they had pasty faeces, and there were many Cryptosporidium oocysts in the faecal smears.

Pancoast's syndrome secondary to thoracic actinomycosis.

Pancoast's syndrome is almost exclusively caused by a malignant apical lung tumor invading the structures of the thoracic outlet. We report a case of thoracic actinomycosis as a cause of Pancoast's syndrome. A 65 y/o bm presented with a 6 month history of nonproductive cough, weight loss, a left upper lobe infiltrate, and a positive PPD of 20 mm. He failed to improve with triple antituberculous therapy for 3 months with worsening of left upper lobe disease. CT scan of the chest showed a mass lesion of the left upper lobe. Bronchoscopy with BAL and biopsy as well as percutaneous fine needle aspiration failed to reveal a diagnosis. Patient developed Pancoast's syndrome characterized by reflex sympathetic dystrophy with pain, swelling, and numbness of left shoulder, arm, and hand. A thoracoscopic left upper lung biopsy was performed and histologic examination revealed sulfur granules containing filamentous organisms characteristic of Actinomyces species. All sections were negative for malignancy. AFB stain and culture were negative. Patient was clinically cured following a 6-month course of penicillin with resolution of the left upper lobe mass. Although rare, thoracic actinomycosis must be considered in the differential diagnosis of Pancoast's syndrome. This case emphasizes the importance of obtaining a precise etiologic diagnosis before a treatment decision is made.

Hot tub legionellosis.

Legionella pneumophila is the cause of Legionnaires' disease, and Pontiac fever, an influenza-like condition without pneumonia. We present a case of Pontiac fever after exposure to a hot tub contaminated with L pneumophila. A 37 y/o wf presented to the office with acute onset of sore throat, fever, headache, and myalgia. Patient was hospitalized 3 days later because of worsening shortness of air. Chest x-ray was normal. Patient was treated with 2 days of IV erythromycin and was discharged home on oral erythromycin. Her Legionella IFA was 1:16,384. Two days later, she developed chest tightness, pleuritic chest pain, and increasing shortness of air but did not have any cough or sputum production. She was re-hospitalized with a diagnosis of Pontiac fever and treated with IV erythromycin plus oral rifampin. A repeat chest x-ray remained normal. After a detailed epidemiologic history was obtained, it was noted that she became ill after using a hot tub, which her two children also used and they themselves developed a self limited illness. Water from the hot tub was positive for L pneumophila by DFA, culture, and PCR. Patient improved gradually with therapy and was discharged home. This report emphasizes the importance of a complete epidemiologic history in the diagnosis of respiratory infections. It also demonstrates that aquatic environment can be contaminated with Legionella and serve as a source of infection.

Diagnosis of Legionella pneumophila, Mycoplasma pneumoniae, or Chlamydia pneumoniae lower respiratory infection using the polymerase chain reaction on a single throat swab specimen.

Diagnosis of Mycoplasma pneumoniae and Chlamydia pneumoniae lower respiratory infections using DNA amplification by polymerase chain reaction (PCR) on throat swab specimens has been reported. In this study we determined the sensitivity of the detection of Legionella pneumophila in simulated throat swab specimens by PCR. Next, we compared the sensitivity and specificity of a single throat swab PCR with the current tests for diagnosis of Legionella spp., M. pneumoniae, and C. pneumoniae in patients with lower respiratory tract infections. Patients' work-up included: (a) throat swab specimen for Legionella spp., M. pneumoniae, and C. pneumoniae PCR; (b) throat swab specimen for C. pneumoniae culture; (c) sputum specimen for L. pneumophila direct fluorescent antibody and culture; (d) urine specimen for L. pneumophila serogroup 1 antigen detection; and (e) serum specimen for L. pneumophila, M. pneumoniae, and C. pneumoniae acute and convalescent antibody titers. A total of 155 patients with lower respiratory infection were enrolled in this prospective study. Throat swab PCR was positive for Legionella spp. in five of the six patients with legionellosis, indicating the presence of this organism in the oropharynx of patients with Legionnaires disease. Mycoplasma pneumoniae PCR was positive in eight of the nine patients with mycoplasma infection. Chlamydia pneumoniae PCR was positive in the two patients with C. pneumoniae infection. None of the other 138 patients with negative PCR had other positive confirmatory tests for respiratory infection by these three organisms (100% specificity). PCR was able to detect 15 of the 17 infected (88.2%). Results of this investigation indicate that PCR on a single throat swab specimen is a rapid, sensitive, and specific test that may greatly simplify the diagnosis of lower respiratory infection caused by Legionella spp., Mycoplasma pneumoniae, or C. pneumoniae.

Pseudomonas pickettii pneumonia in a diabetic patient.

Pseudomonas pickettii is a nonfermenting gram negative rod closely related to Pseudomonas aeruginosa that rarely causes human disease. We describe a case of P pickettii pneumonia in a 41-year-old diabetic patient. Two months prior to admission, patient was treated for a methicillin resistant Staphylococcus aureus pneumonia. Present illness started 2 days prior to admission with fever, chills, pleuritic chest pain, and productive cough. Chest x-ray showed a right lower lobe infiltrate with effusion. Thoracocentesis of the right chest brought a transudative fluid. P picketii was isolated from pleural fluid and blood. The patient was initially treated with aztreonam and piperacillin and therapy was changed to ampicillin according to sensitivity results. The pneumonia resolved after 10 days of antibiotic therapy. Our case is the first reported case of P pickettii pneumonia. P pickettii has been reported to cause nosocomial bacteremias associated with contaminated intravenous products and airway colonization from contaminated respiratory therapy solution. Our patient most likely had oropharyngeal colonization with P pickettii during his previous hospitalization. His underlying illnesses might have predisposed him to aspiration and development of P pickettii pneumonia. This case emphasizes the central role of the microbiology laboratory in the proper identification and sensitivity reporting in the management of respiratory infections caused by unusual organisms, such as P pickettii.

New principles for optimum left ventriculography.

Left ventriculography has become the single most important procedure in the evaluation of cardiac function. This study reevaluated the refinements of catheter and power injector technology to assess recommendations of past years and establish new principles for optimum ventriculography. Ventriculograms from 102 patients undergoing left heart catheterization and coronary arteriography for coronary, valvular, and myocardial heart disease served as the test sample. Three styles of #7F high-flow 110-cm pigtail catheters were utilized. One had 12 sideholes while the other two had six sideholes positioned nearer the base of the curl. Analysis of ventriculographic quality of each angiogram was performed by three of the authors independently and subsequently together. Five variables were analyzed for their effect on the diagnostic quality of the angiogram: 6-hole catheters, 12-hole catheters, volume of contrast, flow rate, and location of injection. Once these analyses were complete, the effect of combinations of these variables was tested to determine their effect on angiographic quality. The first combination included contrast volume and flow rate. The second combination compared contrast volume and flow rate when utilized with 6- or 12-hole catheters. The third combination tested the 6- and 12-hole catheters in the apex or inflow locations. A multivariate contingency analysis was used to define relationships between the variables and the quality of the angiogram obtained. As independent variables, catheter style, volume of contrast, flow rate, and location of injection did not influence angiographic quality. However, the apex as a location of injection was the single most consistently important determinant of ventricular angiographic quality.(ABSTRACT TRUNCATED AT 250 WORDS)

Pacer-induced tachycardia associated with an atrial synchronous ventricular inhibited (ASVIP) pulse generator.

A 68-year-old white male underwent permanent pacemaker implantation with an atrial synchronous ventricular inhibited pulse generator (Medtronic model 2409) because of syncope and abnormal H-V interval of 70 ms. Paroxysmal bouts of pacemaker associated tachycardia were subsequently recorded on several occasions, initiated and terminated by spontaneous ventricular premature beats. The mechanism for the occurrence of the tachyarrhythmia is discussed in detail and the functional characteristics of the pulse generator are described. Replacement of the unit with a different pacer device prevented further occurrence of the arrhythmia.

Pseudo complications of cardiac catheterization: update.

This prospective study was performed to determine whether complications that occur immediately before or after the time of scheduled catheterization are as much disease-related as procedure-related. During 24 months all complications associated with 1,606 diagnostic cardiac catheterizations were recorded if they occurred from 24 hours before the time the procedure was scheduled to 72 hours later, longer if complications were clearly procedure-related. Pseudo complications are spontaneous medical or surgical incidents that occur during the 24-hour period before catheterization is scheduled to be performed. Procedure-related complications are incidents that occur during or after the catheterization procedure. There were 13 (0.81%) procedure-related complications but not deaths. There were 13 (0.81%) pseudo complications including 4 (0.24%) deaths. All complications were similar in nature except for 3 instances of vascular injury, which were procedure-related. Pseudo complications occur as commonly as procedure-related complications and at times are more severe. Complications occurring before catheterization are related to the underlying disease process and not medical intervention. It is likely that similar disease-caused incidents occur after a catheterization and are not necessarily procedure-related.