SEARCH · PubMed Health

Results for “exceptional responders”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Deconstructing Exceptional Responses to Immune Checkpoint Inhibition in Recurrent or Metastatic Head and Neck Carcinoma: A Site-Specific Clinical-Biological Synthesis.

Background: Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is an aggressive malignancy with a historically poor prognosis. Although immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have established a new first-line standard of care, durable clinical benefit is restricted to a minority of patients, while primary or acquired resistance remains a major clinical challenge. This narrative review aims to provide a conceptual clinical-biological synthesis of immunotherapy in R/M HNSCC through an anatomical and biomarker-driven lens, with a focus on characterizing potential shared features of "exceptional responders". Methods: A targeted narrative literature search was conducted across PubMed/MEDLINE and to identify key clinical trials and representative clinical reports of exceptional response to ICIs in R/M HNSCC. The literature was not systematically synthesized to construct a conceptual clinical-biological framework of response and resistance. Results: Landmark clinical data confirm durable survival benefits with frontline pembrolizumab-based regimens in selected PDL-1 positive populations compared to historical chemotherapy. Qualitative appraisal of illustrative cases and translational cohorts suggests a potential biological hypothesis: exceptional responders, defined as patients achieving unexpected, multi-year complete radiological, pathological, or metabolic remissions, often align with a favorable confluence of a pre-existing "hot" or inflamed tumor microenvironment, preserved antigen presentation machinery, and elevated antigenic novelty driven by viral oncoproteins (HPV, EBV) or high mutational/indel burdens. Conversely, primary and acquired resistance are conceptually associated with defects in antigen processing, immunosuppressive cellular barriers, and alternative immune checkpoints. Conclusions: Immunotherapy has fundamentally transformed R/M HNSCC management, yet exceptional single-agent responses remain rare. Rather than a definitive or proven biological biomarker, the proposed blueprint represents an integrative hypothesis highlighting the complex interplay of baseline immune inflammation, genomic features, and viral drivers. Translating these observations into broader clinical benefit will require validated biomarker-driven personalization and rationally designed combination regimens.

Epstein-Barr virus (EBV)↗

PubMed1977

LSD and d-amphetamine effects on fixed interval responding in the rat.

Food-deprived rats were trained to press a key which produced a food pellet for the first press after 3 min had elapsed (FI 3 min). Daily sessions consisted of 10 such intervals. Graded doses of LSD (0.04 - 1.28 mg/kg) and a d-amphetamine (0.5 - 2.0 mg/kg) were given 30 min before sessions. LSD produced a decrease in response rate at doses of 0.32 mg/kg and above, but did not disrupt the typical FI pattern of responding except at the highest dose (1.28 mg/kg). Amphetamine did not significantly alter the overall response rate, but caused a dose-related disruption of the FI response pattern, with previously low response rates increased more than higher rates, and occasional decreases in the previously highest rates. The experiment was repeated using the same rats responding on a multiple FIFR schedule. The presence of a 2000 Hz tone signalled FR periods; the tone was absent during FI periods. During the FR components, a pellet was produced after 30 responses had been emitted. The FI components were unchanged. LSD (0.08 - 0.32 mg/kg) again produced decreases in FI rate without altering the pattern, and amphetamine again altered the FI pattern without significantly changing overall rate.

Animals↗

PubMed1978

Sexual knowledge, attitudes, and practice of Israeli adolescents.

A study of 4,976 high-school students in Israel, representative of this age group for the entire country except for 13 percent who attend religious schools, revealed that about one-third of the boys aged 14-15 and almost one-half of those in the 16-17 age category have had sexual intercourse. The respective figures for girls are 6 percent and 16 percent. Age at onset of sexual activity was found to be higher and the level of knowledge about the same as in reports from the Western world. Students of Oriental origin, as well as those considering themselves religious or traditional tended to be less active sexually, more conservative in their attitudes, and less knowledgeable. In contrast, students of both sexes residing in kibbutzim were found to be more active sexually and more knowledgeable. A double standard for girls was accepted, especially among the female respondents, except in the kibbutzim. A subgroup of girls highly sexually active, in contrast to their own attitudes, has been identified, and possible reasons for this discordance discussed. As sexual activity among teenagers is becoming more prevalent, comprehensive and early sex education school programs should be encouraged.

Adolescent↗

PubMed1978

Acute and chronic effects of cocaine on extinction-induced aggression.

Pigeons worked individually in a chamber containing a response key and a mirror. Pecking on the key was controlled by a multiple schedule in which a brief period of continuous food reinforcement alternated with a 5-minute period of extinction. Under baseline conditions, aggressive behavior (responding on the mirror) occurred at the onset of each extinction period. In Experiment I (acute drug administration), the aggressive behavior was decreased by doses of cocaine that had little or no effect on key pecking. Such food-reinforced responding was disrupted, however, by higher doses of cocaine. An attempt to mimic the disruptive drugs effects by a prefeeding manipulation was unsuccessful. In Experiment II (chronic drug administration), some tolerance developed to the disruptive effects of cocaine on the food-reinforced responding, except at the highest dose tested. There was no clear-cut indication of tolerance to the initial effect of cocaine on the aggressive behavior at any dose.

Aggression↗

PubMed2026

Long-Term Outcomes in Patients With Recurrent Ovarian Cancer and Exceptional Response to PARP Inhibitors.

IMPORTANCE: A subset of patients with platinum-sensitive recurrent ovarian cancer (PS-ROC) treated with maintenance poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have exceptional response. Although licensing recommends continuing PARP inhibitors until progression or unacceptable toxic effects, the optimal duration of PARP inhibitors, and the risks of late progression, myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) in patients with exceptional response are unknown. OBJECTIVE: To determine the long-term outcomes of patients with PS-ROC who have exceptional response to PARP inhibitors, and to explore genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, retrospective cohort study of patients with exceptional response to PARP inhibitors, defined as patients with PS-ROC and progression-free survival (PFS) of 5 years or longer from PARP inhibitor commencement. The study was conducted across 41 sites in 14 countries from January 11, 2023, to November 10, 2025. EXPOSURES: Treatment with PARP inhibitors. MAIN OUTCOMES AND MEASURES: The primary end point was PFS, and secondary end points included overall survival, toxic effects, and dose reductions. RESULTS: A total of 320 patients with exceptional response (mean [SD] age, 56.4 [9.4] years) were included, with a median follow-up of 6.8 years (95% CI, 6.6-7.0 years). The median (IQR) PARP inhibitor duration was 75.0 (64.0-91.0) months. Of patients with exceptional response, 211 (65.9%) received continuous PARP inhibitors, but 109 (34.1%) discontinued: 34 (10.6%) due to physician recommendation, 2 (7.5%) had disease progression beyond 5 years, 22 (6.9%) had toxic effects, 17 (5.3%) for patient preference, and 12 (3.8%) for another reason. The 7.5-year and 10-year PFS rates were 88.8% (95% CI, 84.5%-93.3%) and 78.7% (95% CI, 70.5%-87.9%), respectively. Among the patients, 85 (26.6%) discontinued PARP inhibitors for reasons other than disease progression, with a 10-year PFS of 90.1% (95% CI, 80.6%-100%) vs 72.5% (95% CI, 60.3%-87.2%) for those who continued taking PARP inhibitors. Five patients (1.6%) were diagnosed with late-onset MDS/AML. Patients with exceptional response were enriched for variants in the BRCA1 RING domain and the BRCA2 DNA-binding domain. CONCLUSIONS AND RELEVANCE: In this cohort study, most patients with exceptional response to PARP inhibitors remained progression free, including those who discontinued PARP inhibitors without progression. The risk of late-onset MDS/AML was low. These results can guide counseling on the duration of maintenance PARP inhibitors in patients with exceptional response and suggest that functional cure may be possible in patients with PS-ROC and exceptional response to PARP inhibitors.

Humans↗

PubMed1979

Management of neurogenic bladder in infancy and childhood.

Sixty-two patients, age twelve years and under, were treated for incontinence due to neurogenic bladder secondary to spina bifida (58) or trauma (4) with a follow-up period of three to thirty-two months (mean, ten months). In early life, patients were managed with the Credé maneuver (18 patients). Older children were managed with intermittent clean catheterization (44 patients) with or without pharmacologic agents. Continence was achieved with intermittent clean catheterization in 77 per cent, thus enabling these children to be more acceptable to their peers and in many cases attend schools from which they had previously been excluded because of urinary incontinence. With the Credé maneuver, renal deterioration was noted in 11 per cent on follow-up IVP, and in 2 per cent of the patients on intermittent clean catheterization. Recurrent asymptomatic bacteriuria occurred in 33 per cent of those with the Credé maneuver and in 55 per cent of the patients using intermittent clean catheterization. The use of antibiotic bladder irrigations reduced this incidence to 5 per cent. All patients with renal deterioration except one responded to intermittent clean catheterization; this patient was treated with cutaneous vesicostomy. Urodynamic assessment was performed in 15 patients, and this diagnostic tool assisted in the therapeutic management of these children.

Child↗

PubMed1977

Effects of carbohydrates on carbon dioxide excretion in patients with airway disease.

Thirteen patients with stable airway disease were fed a diet high in carbohydrates, and 35 minutes later metabolic and ventilatory effects were observed. The six patients who did not retain carbon dioxide increased their mean respiratory quotient from 0.86 +/- 0.07 to 1.03 +/- 0.04, their mean minute ventilation from 10.3 +/- 3.0 to 12.8 +/- 4.0 L/min, mean carbon dioxide production from 0.23 +/- 0.04 to 0.29 +/- 0.02 L/min, and mean oxygen consumption from 0.27 +/- 0.07 to 0.29 +/- 0.03 L/min (all P less than 0.05). The arterial carbon dioxide tension (PaCO2) did not change significantly from baseline values. The seven patients who retained carbon dioxide responded similarly, except that their mean arterial oxygen pressure (PaO2) increased significantly from 50.9 +/- 4.4 to 57.7 +/- 5.5 torr (P less than 0.05). In addition, the mean PaCO2 increased from 54.5 +/- 6.4 to 54.9 +/- 6.4 torr (not significant). We conclude that the increased endogenous carbon dioxide load resulting from a meal high in carbohydrates is well tolerated by most patients with chronic airway disease.

Carbon Dioxide↗

PubMed1975

Method for measuring brain tissue pressure. Response to alteration in pCO-2 systemic blood pressure, and middle cerebral artery occlusion.

The authors report a method for measuring total local brain tissue pressure (BTP) using a miniature catheter transducer stereotaxically introduced into the white matter of the cat's cerebrum. Quantitative rapid phasic pressure changes were satisfactorily demonstrated. Due to some drift of baseline of the transducers and inability to perform in vivo calibration, reliable long-term quantitative pressure measurements sometimes could not be studied. The BTP from each cerebral hemisphere and the cisternal pressure (CP) were monitored during alterations of pCO-2 and systemic blood pressure, and distilled H20 injection prior to and after right middle cerebral artery (MCA) ligation. The catheter transducers functioned well on chronic implantation for up to 6 weeks. Compared to the chronically implanted catheters, acutely implanted catheters responded identically except for drift. The response of intracranial pressure and CP to MCA occlusion, alterations in pCO2, and systemic blood pressure were similar. No BTP gradients appeared in response to MCA ligation, hypercapnia, hypertension, or progressive swelling of the resulting infarction.

Animals↗

PubMed1978

Controlled trial of bronchodilator-mucolytic aerosols, combined and separate.

In seven of 30 ambulatory asthmatics the inhalation of 10% acetylcysteine reduced the FEV1 by more than 10% (range: 14% to 53%). Inclusion of isoproterenol (0.05%) reversed this depression over the entire trial in six of these subjects, while the seventh responded similarly except for the last measurement. It is concluded that the addition of isoproterenol to an acetylcysteine aerosol in the above ratio can eliminate the ventilatory impairment induced by the latter and is therefore indicated for those patients with chronic obstructive lung disease who benefit from a mucolytic agent.

Acetylcysteine↗

PubMed1979

Evaluation of cefaclor and amoxycillin in the treatment of acute otitis media.

Twenty-eight patients with acute otitis media were treated in a random double blind manner with either amoxycillin or cefaclor. The predominant organisms isolated were H. influenzae and S. pneumoniae. All patients responded satisfactorily except one, treated with cefaclor, whose compliance with the regimen was very doubtful. One instance of mild elevation of SGOT and one case of mild erythematous rash occurred in each treatment group. In this limited study, cefaclor appeared comparable to amoxycillin in the treatment of acute otitis media.

Acute Disease↗

PubMed1975

A review of the effects of diazepam on cognitive and psychomotor performance.

Studies evaluating the effects of diazepam (Valium) on psychomotor and cognitive functions are reviewed an integrated. The importance of the full and clear documentation of such drug effects lies in the wide usage of diazepam today for a variety of medical, psychiatric, and dental purposes. The various tasks used to assess drug effects were classified into six major groups based on apparent similarity of functions tapped. These groupings are: reflex speed; critical flicker fusion threshold; attention and vigilance; decision making; learning and memory; psychomotor performance. In all functions except simple reflexive responding; some indications of impaired performances were reported, the results being most definitive for the critical flicker fusion where even small doses lowered the threshold and for a slower performance on letter cancellation tasks. There appeared to be some interaction between diazepam and alcohol although the nature of this interaction is still unclear. Because of the extensive use of both of these drugs and the possibility of a synergistic or a potentiation effect, it is important that this area receive further study. It was suggested that future studies either control for or analyze the data to assess the possible interactive effects of diazepam with subject variables such as sex, personality type, and for population characteristics. These variables have been shown to affect responses in other studies and hence could also interact with cognitive and psychomotor performance. It was noted that most of the studies reviewed used normal, healthy, male volunteer subjects and may not be comparable to the clinical populations for whom the drug is typically prescribed.

Attention↗

PubMed1975

Effects of anesthesia, surgery and inflammation upon host defense mechanisms. I. Effects upon the complement system.

Complement protein levels and C7 hemolytic activity were measured in four individuals following anesthesia and surgery, and in a group of 20 patients with inflammatory diseases. Seven of the eight complement components studied characteristically were elevated, most dramatically C1s and C3PA. Elevation of C1s often was greater than elevation of C1q, displaying an independent variation of C1s and C1q in both postoperative and inflammatory disease patient groupds. The major increases of C components were seen subsequent to the peak C-reactive protein response, as was the occurrence of the 'reactor state', a propensity to formation of C56 which surprisingly was associated with increased levels of C7. Levels of properdin frequently were reduced postoperatively. It is concluded that multiple complement components, with the notable exception of properdin, respond as acute phase reactants which are elevated and changed in proportion postoperatively and during inflammatory disease.

Anesthesia, General↗

PubMed1979

Cellular co-operation in the production of human leucocyte inhibitory factor by lymphocyte subpopulations stimulated with antigens and allogeneic cells.

The ability of antigens and allogeneic cells to induce lymphokine synthesis and cellular co-operation in lymphokine production was investigated. Human peripheral blood lymphocytes were separated into T- and B-cell populations by sheep red blood cell rosette formation and centrifugation on Ficoll--Isopaque. The cells were then stimulated with PPD, SK-SD, candida and with allogeneic cells. The presence of leucocyte inhibitory factor (LIF) in the culture supernatants was tested by the agarose migration method. The results indicated that T lymphocytes produced LIF after stimulation with antigens and allogeneic cells. In addition, B cells responded to PPD. Except for PPD the stimulants did not induce significant T-cell LIF production in the absence of monocytes. Only autologous monocytes enhanced LIF synthesis after antigenic stimulation, whereas in mixed lymphocyte cultures allogeneic monocytes were as effective as autologous ones. The monocyte helper effect was mediated by soluble factors in mixed lymphocyte cultures and by soluble factors and direct cell--cell contact in antigen-stimulated cultures. No co-operation between T and B lymphocytes was found. B cells did not enhance LIF production by T cells, nor could T cells induce a B-cell response to antigens or allogeneic cells.

Antigens↗

PubMed1979

Peritoneal lavage in the horse.

Eight horses ranging in age from 4 days to 9 years were treated for peritonitis. Escherichia coli was isolated in four cases and Nocardia sp in one case. In each case, a catheter placed in the peritoneal cavity allowed drainage of a large amount of purulent fluid. Retrograde peritoneal lavage was performed through a Foley catheter or medical tubing, using Ringer's lactate solution containing kanamycin, povidone iodine, or nitrofurazone. All except two horses responded well to repeated lavage.

Animals↗

PubMed1979

Augmentation of hemagglutination-inhibition (HI) antibodies in gilts of breeding age by large dosages of human A/New Jersey/76 influenza vaccine.

Fifteen gilts of breeding age were studied. Four received three 4 ml. doses three weeks apart of an experimental killed swine influenza vaccine containing A/Swine/ill/65 antigen, four received three ml. doses three weeks apart of a human influenza vaccine containing A/New Jersey/76 antigen and three received two doses of human influenza vaccine followed by a 3 ml. third dose of experimental swine influenza vaccine. All except one vaccinate responded to two doses of vaccine by the time of the third dose of vaccine. HI titers were highest four weeks after the third dose of vaccine. Geometric mean titers were highest in animals receiving human influenza vaccine containing A/New Jersey/76. Titer profiles dropped markedly by 60 days after the third vaccination.

Animals↗

PubMedDate not supplied

Synchronisation of oestrus and fertility in buffaloes using a prostaglandin analogue.

Cloprostenol, a prostaglandin analogue, was administered intramuscularly to a total of 35 cycling buffalo cows and heifers in two doses, each of 0.5 mg, given 11 days apart. Out of five cows and 12 heifers subjected to observations after the second injection of cloprostenol (day 0), all except one heifer responded. Signs of oestrus were most marked on days 3 or 4. Eighteen treated heifers were kept with buffalo bulls for four days after the second injection while a control group of nine heifers was kept with bulls for 21 days. The first-service conception rate, diagnosed by rectal palpation at 60 days, was 33 1/3 per cent in both groups. Twelve treated heifers were artificially inseminated at 72 and 96 hours after the second injection of cloprostenol, using fresh semen diluted in egg yolk--citrate extender. The first service conception rate at 60 days was 30 per cent.

Animals↗

PubMed1977

[Characteristics of the functional maturity of the insular apparatus of the human pancreas during intrauterine development].

The reactivity of human foetal pancreas was determined by the increase of insulin secretion in vitro in response to the effect of glucose, arginine, theophylline, cyclic AMP and somatotrophic hormone (STH). The results of the experiments have shown that the beta-cells of the islet system in the pancreas of 7-9 weeks old embryos are as yet not able to respond to the main physiological stimulus, glucose, but respond already to cAMP, STH, arginine with glucose. The glands of 10-14 weeks old foetuses are already able to react to glucose and respond to all other stimuli, except arginine. Taken for comparison, the glands of 19-22 weeks old foetuses respond to glucose by the increase of insulin secretion.

Arginine↗

PubMed1977

Aetiocholanolone and prednisolone therapy in patients with severe bone-marrow failure.

Ten patients with bone-marrow failure from myelofibrosis, aplastic anaemia, paroxysmal nocturnal haemoglobinuria, and "hairy cell" leukaemia, who had failed to respond to androgens and/or glucocorticosteroids, were treated with a combination of aetiocholanolone and prednisolone. All patients except one with aplastic anaemia responded with an increase in reticulocytes, haematocrit, red blood cell mass, and blood neutrophils and platelets. These data suggest that aetiocholanolone, and similar 5beta-hydroxy steroids, may be valuable in treating certain patients with chronic marrow failure.

Adult↗