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PubMed2026

Evolving Role of Immunotherapy in Advanced Esophageal Squamous Cell Carcinoma: Are Programmed Death-Ligand 1 (PD-L1) Cutoffs Still Relevant?

Immune checkpoint inhibitors have transformed the management of advanced esophageal squamous cell carcinoma (ESCC) across first-line, second-line, and perioperative settings. Programmed death-ligand 1 (PD-L1) expression has served as the principal biomarker guiding patient selection for these agents, yet it is measured inconsistently across trials and antibody platforms, and its predictive value has come under renewed scrutiny as follow-up data have matured. This review synthesizes the pivotal randomized trials that established anti-programmed cell death protein-1 therapy in ESCC, critically appraises the pooled and patient-level meta-analyses that have re-examined outcomes across biomarker subgroups, and situates recent regulatory reassessment of PD-L1 thresholds within this broader evidence base. Assay heterogeneity between scoring systems, discordance across antibody clones, and the biological distinction between PD-L1 as a prognostic versus a predictive marker are examined as sources of continued uncertainty. The review concludes by considering emerging genomic and microenvironmental biomarkers that may eventually complement or refine PD-L1-based patient selection, and offers a framework for interpreting a single expression threshold as an approximate, assay-dependent stratifier rather than a precise biological boundary.

combined positive score↗

PubMed1976

Methotrexate (NSC-740) with citrovorum factor (NSC-3590) rescue, alone and in combination with cyclophosphamide (NSC-26271), in ovarian cancer.

In a randomized study, 35 patients with advanced-stage epithelial ovarian cancers with progressive disease after prior single alkylating agent or combination-agent chemotherapy were treated with either intermediate high-dose methotrexate-citrovorum factor rescue alone or methotrexate-citrovorum factor rescue plus cyclophosphamide. Objective responses to both "second-line" chemotherapeutic regimens were observed. The objective response rate of 43% observed with the methotrexate-citrovorum factor plus cyclophosphamide treatment was superior to that achieved with methotrexate-citrovorum factor given alone. This combination of agents is the most effective second-line chemotherapeutic regimen for ovarian cancer that we have yet tested and we are therefore optimistic about its possibilities as first-line therapy. After early dosage modifications, serious toxic side effects were rare in this group of patients who had had extensive prior therapy.

Adult↗

PubMed1975

Investigations of allergic status and blood counts in Chinese patients receiving daily or intermittent rifampicin in Hong Kong.

In a controlled trial in Hong Bong, 575 Chinese patients with pulmonary tuberculosis whose treatment with first-line regimens had failed were allocated at random to the following retreatment regimens of chemotherapy. (1) Rifampicin plus ethambutol daily (ER7). (2) Rifampicin plus ethambutol twice a week (ER2). (3) Rifampicin plus ethambutol once a week (ER1). (4) Rifampicin plus ethambutol daily for 2 months and then once a week (ER7ER1). (5) Ethionamide plus pyrazinamide plus cycloserine daily for 6 months and then ethionamide plus pyrazinamide daily (EtZC), as a control regimen. Answers to a questionnaire on allergic disease, the results of prick tests with standard allergens, ABO blood grouping, size of tuberculin response during chemotherapy, and a rifampicin patch test showed no associations with the occurrence of adverse reactions to daily or intermittent rifampicin. Mantoux testing during chemotherapy provided no evidence of an immunosuppressive effect of rifampicin. Mean platelet counts at 12 months were significantly lower than those at 3 months on the two once-weekly regimens (ER1, ER7ER1) and on the control regimen (EtZC), although still within normal limits. At 3 months, but not at 12 months, mean platelet counts on the two once-weekly regimens were significantly lower 6 hr after a dose of the regimen than they were before the dose.

ABO Blood-Group System↗

PubMed1992

[Successful management of choriocarcinoma of the testis with brain metastasis: a case report].

A 32-year-old Japanese male consulted a clinic complaining of gynecomastia. Right painless scrotal swelling was also detected. Right high orchiectomy was performed, then the surgical specimen was histopathologically confirmed as choriocarcinoma and mature teratoma. The imaging revealed cerebral, pulmonary, retroperitoneal metastases. After 3 courses of combination chemotherapy with cisplatin, etoposide and peplomycin (PEP therapy), the brain metastasis completely disappeared and the serum titer of the tumor markers such as beta-HCG became normal. The regression rates of lung and retroperitoneal metastases were 68% and 27%, respectively. Therefore, retroperitoneal lymph node dissection was performed. After the 5th course of PEP therapy, lung metastases disappeared completely. Until the present, no evidence of disease has persisted. The PEP therapy, which is a salvage therapy for refractory testicular cancer, was performed as first-line chemotherapy in this case. It was an excellent modality against choriocarcinoma, along with the surgical treatment.

Adult↗

PubMed1992

Antihypertensive therapy: new strategies beyond blood pressure control.

Mild-to-moderate essential hypertension is the most common medical problem seen by physicians in Western populations, and pharmacologic antihypertensive therapy is now usually undertaken. Clinical trials have shown that lowering of elevated blood pressure using diuretics and beta-blockers reduces cardiovascular morbidity and mortality. Despite these benefits, the trials have provided no convincing evidence that the incidence of coronary artery disease or its complications is reduced: Treated hypertensive patients remain at increased cardiovascular risk compared with untreated normotensive subjects. Possible explanations for this disappointing outcome are that the drugs used may themselves have negative effects on serum lipids, glucose, and insulin resistance, thereby outweighing their antihypertensive benefits. An equally important role in this respect may be played by the diseases and therapies most commonly found in association with mild-to-moderate hypertension: hyperlipidemia, type II diabetes, coronary artery disease, left ventricular hypertrophy, cardiac arrhythmias, peripheral arterial disease, and nephropathy. Such conditions may be potent determinants of what constitutes the optimal first-line choice of antihypertensive therapy. Furthermore, the negative effects that antihypertensive drugs can have on quality-of-life factors may result in noncompliance and ineffective long-term treatment. Therefore, in a new therapeutic approach to the treatment of high blood pressure, it would be logical to base antihypertensive therapy on strategies that not only lower the blood pressure but that have beneficial impacts on hemodynamics, vascular and cardiac structure, metabolism, and quality-of-life issues.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗

PubMed1992

Effects of antihypertensive treatment with beta-blockers on glucose metabolism.

The beneficial effects of beta-blockers on morbidity and mortality in both essential hypertension and diabetes mellitus have been demonstrated in several antihypertensive trial. Recently, negative side effects of beta-blockers on glucose metabolism have been suggested that could limit their wide-spread use. However, on detailed analysis, any side effects of beta 1-selective beta-blockers on glucose metabolism do not appear to be relevant for clinical practice and hence do not restrict the use of these agents as first-line antihypertensive drugs in diabetic and nondiabetic patients.

Adrenergic beta-Antagonists↗

PubMed1992

Influence of diuretics, calcium antagonists, and alpha-blockers on insulin sensitivity and glucose tolerance in hypertensive patients.

Treatment with thiazide diuretics causes impaired glucose tolerance, biochemical diabetes, and insulin resistance. The effect of diuretics on glucose tolerance is clearly dose-related. Spironolactone does not impair glucose tolerance, even at high dosage, but differences among other diuretics could be due to comparisons at doses that are not equal. Diuretic-induced changes in glucose metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs even when relatively low doses of thiazide are combined with potassium-sparing agents. The effects of diuretics on glucose homeostasis are in large part and probably entirely reversible. These disturbances of glucose metabolism have been detected only by detailed biochemical testing, and their clinical relevance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In nondiabetic subjects, diuretics rarely cause or trigger a serious hyperosmolar nonketotic diabetic syndrome. Otherwise, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long term. Evidence from large outcome trials suggests that biochemical diabetes, glucose intolerance, and insulin resistance do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes unless their use is essential. Otherwise, a low dose of thiazide remains as excellent choice for first-line antihypertensive therapy. Dihydropyridine calcium antagonists, diltiazem, and verapamil appear to have no important effects on glucose homeostasis. There is very limited evidence that selective alpha-antagonists increase insulin sensitivity. The importance of metabolic differences between drug classes will be established only by comparative outcome trials with coronary events as the end point.

Adrenergic beta-Antagonists↗

PubMed1992

Antipyretic therapy in the febrile child.

General principles of thermoregulation, the pathophysiology of fever, controversies concerning the use of antipyretic therapy, and nonpharmacologic and pharmacologic treatments commonly used for antipyresis in the pediatric population are reviewed. Several arguments can be made for not ameliorating the febrile response. Fever is an important diagnostic and prognostic clinical sign that may have beneficial effects for the host. In addition, body temperatures of < or = 41 degrees C (105.8 degrees F) are relatively harmless. Reasons for treating fever include patient discomfort, the potential for adverse sequelae, the possibility of seizures, and the possibility that fever could affect the pharmacokinetic profiles of drugs. Nonpharmacologic treatment for fever includes environmental measures to enhance dissipation of body heat and sponging. Aspirin and acetaminophen are the agents used most frequently for antipyresis in pediatric patients. However, aspirin use in children with a viral illness has been associated with development of Reye's syndrome. As a result, its use in children has declined in the United States. Acetaminophen is relatively free of adverse effects and is considered first-line pharmacologic antipyresis therapy. Ibuprofen suspension should be considered as second-line antipyretic therapy. Combination therapy with acetaminophen and aspirin may be considered if the patient fails to respond to other nonpharmacologic and pharmacologic therapies; however, combination therapy may result in increased risk of drug toxicity, increased probability of adverse reactions, and increased risk of intoxication. Aspirin, acetaminophen, and ibuprofen are equally effective for antipyresis in pediatric patients. However, because acetaminophen is the safest medication, it is currently the therapy of choice.

Acetaminophen↗

PubMed1992

[Multidirectional instabilities and hyperlaxity of the shoulder].

Multidirectional instability is an unusual entity which is frequently missed in the context of unstable shoulder. The diagnosis of this condition may be difficult and is based on demonstration of basic anatomical lesions, usually acquired: capsular distension and damage to the inferior glenohumeral ligament responsible for the inferior component of the instability. Despite a suggestive clinical history, the positive diagnosis is based on a very detailed clinical and radiological examination, performed under general anaesthesia if necessary, in order to define the preferential direction of instability. Conventional and CT arthrography are of undeniable diagnostic and therapeutic value in the context of assessment. First-line treatment should be conservative. When surgery is indicated, it may consist of a combination of bone grafts and capsulorraphy, as described by C.S. Neer.

Humans↗

PubMedDate not supplied

Malaria prophylaxis: taking aim at constantly moving targets.

The prevention of malaria infections is one of the most important functions that any clinician can perform for those traveling to tropical geographic regions where malaria risks are present. The prophylaxis question has become complicated by continued emergence of chloroquine-resistant strains of Plasmodium falciparum, the recent appearance of Plasmodium vivax resistance, and the availability of a wide choice of antimalarial pharmaceuticals. Chemoprophylaxis may produce different toxicities among various patient populations. With increasing numbers of women who travel during their professional lives, there are potential implications for using chemoprophylaxis during pregnancy. Children are unable to tolerate certain antimalarials because of toxicities unique for them. In some instances, the safest and most palatable formulations for children are not even available in the United States and must be purchased in Canada or elsewhere. Reliance upon chemoprophylaxis alone has proven to be increasingly futile. With the introduction of new repellent formulations and nontoxic insecticides for use on clothing or bed netting, there are non-pharmacologic adjunctive measures which can now be considered first-line for the prevention of malaria infections.

Amodiaquine↗

PubMed1992

[Results of trabeculectomy in congenital glaucoma].

Congenital glaucoma has a very serious prognosis. It represents the first cause of blindness in Tunisian children. Trabeculectomy introduced by Cairns in 1968, was initially proposed as second-line treatment in congenital glaucoma surgery. It has now become more frequently used as first-line treatment in this indication. We have already used this technique directly in 35 children suffering from congenital glaucoma with a total of 54 eyes. Forty four eyes underwent a single operation, ten eyes underwent two to four trabeculectomies. Then study of these cases with a mean follow up of 24 months shows an overall success rate of 64% after one trabeculectomy, with or without additional medical treatment. The study of tonometric diagrams shows that the successful results obtained after 3 months persisted in the long term. Trabeculectomy gives better results in congenital glaucoma with intraocular pressure greater than 40 mmHg. Repeated operations are sometimes necessary. In these cases, postoperative subconjunctival 5 fluorouracil (SFU) did not improve the surgical outcome.

Child↗

PubMed1992

[Endoscopic treatment of vesico-ureteral reflux after reimplantation of the ureter (transplants excluded)].

O'Donnell's technique was used to treat 9 refluxing ureteric units after surgical reimplantation of the ureter in 8 patients (mean age: 45 years) between May 1986 and January 1991. The reimplantation was performed according to Cohen's technique in 5 cases (including ureteric remodelling in one case), Leadbetter's technique in 2 cases (including ureteric remodelling in one case), the Campos Freire technique in 1 case and a direct reimplantation in 1 case (with Boari). The reflux was grade II for 1 ureter, grade III for 54 ureters, grade IV for 2 ureters and grade V for 1 ureter. A single injection was performed in 5 patients and multiple injections were required in 3 patients. An associated bladder neck incision was performed in 2 male patients. No complications were observed. Correction of reflux was obtained for 8 ureteric units, i.e. 87% success with a mean follow-up of 28 months. The failure corresponded to the case of grade V reflux in a megaureter reimplanted with remodelling. The authors recommend that endoscopic treatment of reflux be performed as first-line treatment for reflux of reimplanted ureters because of the simplicity and efficacy of this technique.

Adult↗

PubMed1992

[Usefulness of converting enzyme inhibitors in the diagnosis of arterial hypertension].

Angiotensin-converting enzyme (ACE) inhibitors are now widely used as first-line treatment of essential hypertension. Their effectiveness is potentiated by a low-salt diet and, above all, by the simultaneous prescription of diuretics. When secondary hypertension is suspected, ACE inhibitors are a good pharmacological tool to study the renin-angiotensin system. Since activation of this system is the main mechanism responsible for renovascular hypertension, ACE inhibitors are very useful for diagnosis. Conversely, blood pressure is not influenced by ACE inhibitors in primary hyperaldosteronism because of the low plasma renin and angiotensin II levels. Pheochromocytoma activates the renin-angiotensin system, and ACE inhibitors combined with beta-blockers enable the hypertension to be controlled prior to surgical treatment of the tumour. Finally, ACE inhibitors can be used to explore the renin-angiotensin system in the experimental model of renovascular hypertension and therefore contribute to our knowledge of the complex pathophysiology of this most frequent type of secondary hypertension.

Adrenal Gland Neoplasms↗

PubMed1992

[Rhabdomyosarcoma of the prostate. Diagnostic course and current therapy. Report of a case of a 17-year-old boy].

The authors report a case of rhabdomyosarcoma in a 17 year old boy which recurred after combination chemotherapy and radical prostatectomy, followed by death of the patient due to haematological complications of second-line chemotherapy. The diagnosis of these rhabdomyosarcomas is facilitated by the various immunohistochemical stains now available. Chemotherapy is undeniably effective and, combined with surgery and radiotherapy, ensures a 5-year survival of 47% to 93% depending on the stage. The first-line chemotherapy avoids the need for radiotherapy in the early stages and allows less mutilating surgical procedures, while maintaining the survival rate.

Adolescent↗

PubMed1992

[Value (and limitations) of the RAST fx5 in pediatric allergological practice].

RAST f x 5 (CAP-system, Pharmacia), an in vitro assay testing a mixture of 6 food antigens, was systematically applied to 400 children and adolescents with respiratory pathologies possibly of allergic origin. The clinical aspects of the 293 test-negative patients were compared with those of the 107 positive cases. Furthermore, 84 positive sera were also evaluated against each of the 6 antigens regrouped in the f x 5. In this population with allergic respiratory diseases, the most frequently positive tests reacted with antigens of plant origins: wheat, peanut and soybean. From an economic point of view, first-line use of f x 5 markedly reduced the cost of a systematic study of food allergens, whose clinical justification remains to be demonstrated.

Adolescent↗

PubMed1976

Clindamycin: an evaluation of its role in dental patients.

A review of the etiology of orofacial infections, of the pharmacology and spectrum of clindamycin and its associated complications, and a treatment plan for orofacial infections have been presented. On the basis of the data presented, it would seem that except for proved B fragilis infections, clindamycin is not a first-line drug for infections of the orofacial region. There are, however, indications for its use that have been presented. The serious complications associated with its use have also been presented. A high index of suspicion must be maintained regarding the development of these complications if clindaymcin is to be used.

Bacterial Infections↗

PubMed1977

Drug prescribing in rheumatoid arthritis in Otago.

The drug therapy prescribed for a group of 50 patients with rheumatoid arthritis in Otago prior to specialist referral was examined. Thirty-two patients were receiving some first-line anti-inflammatory drugs and six were receiving no therapy at the time of their first hospital clinic visit. Salicylates had been prescribed first in only 16 of the 50 patients while this drug had been withdrawn because of side effects in about one-third of the patients who had been treated with it prior to specialist referral. Seven patients had received phenylbutazone and six corticosteroids as the first treatment for their rheumatoid arthritis. About one-third of the patients were receiving more than one anti-inflammatory drug at the time of their initial clinic visit.

Adult↗

PubMed1979

Bretylium tosylate: a review.

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, drug interactions and dosage of bretylium tosylate, a recently approved antiarrhythmic agent, are reviewed. Bretylium tosylate is used to treat life-threatening ventricular arrhythmias, principally ventricular fibrillation and ventricular tachycardia, that have not responded to treatment with first-line antiarrhythmic agents. The drug has a direct positive inotropic effect on the myocardium and blocking effect on postganglionic sympathetic nerve transmission. The drug is poorly absorbed orally, requiring either i.m. or i.v. administration. Drug excretion occurs primarily through the kidney, necessitating dosage modification in renal disease. Hypotension is the most commonly observed adverse reaction to bretylium tosylate. Rapid i.v. administration may cause severe nausea and vomiting, and i.m. injection at the same site may cause atrophy and necrosis of muscle tissue. Quinidine and procainamide may potentiate the hypotensive effects of bretylium. Bretylium will aggravate digitalis-induced arrhythmias. Bretylium's use in resistant ventricular tachyarrhythmias requires close clinical monitoring.

Arrhythmias, Cardiac↗