Subsequent Full Recovery Research Articles

Real-world experience in initiation of treatment with the selective cardiomyosin inhibitor mavacamten in an outpatient clinic cohort during the 12-week titration period.

Lately, mavacamten emerged as a new therapeutic option for symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM). Clinical trials revealed reduction of serum biomarkers, and left ventricular outflow tract (LVOT) obstruction, as well as an improvement in clinical symptoms and exercise capacity. Nevertheless, clinical experience and manageability of patients in a real-world setting is still lacking. 22 patients with symptomatic oHCM (54.5% male, age 58.5 ± 16.2years) and elevated LVOT gradients were started on mavacamten between March 2023 and June 2024. All patients were New York Heart Association (NYHA) class II or higher. Seven patients were excluded from primary analysis due to comedication with Angiotensin-converting-enzyme-inhibitors or Angiotensin-II receptor blockers. Cardiac imaging, laboratory work-up and clinical evaluation were assessed at three visits during the 12weeks initiation phase; Dosing of mavacamten was adjusted according to manufacturer's recommendations. At 12weeks, the majority of patients described a significant improvement of their quality of life. Work-up at 12weeks revealed a significant reduction of serum biomarkers and LVOT gradients. In four patients, mavacamten needed to be temporarily paused due to clinical complaints or transient left ventricular ejection fraction deterioration below 50% with subsequent full recovery. We provide first insights into the usage of mavacamten in oHCM patients during the titration period in a real-world setting. Clinical findings are in line with previous clinical trials. In accordance with current recommendations, we highlight the need for standardized follow-up of patients on mavacamten treatment.

Venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in metastatic choriocarcinoma during systemic chemotherapy: Case report

Rationale: Gestational trophoblastic neoplasms are rare and include multiple different types of tumors such as hydatidiform moles, placental site trophoblastic tumors, and choriocarcinoma. Metastatic choriocarcinoma is well described with an excellent prognosis when treated appropriately with chemotherapy. The most common location for metastatic disease is the lungs which can unfortunately lead to severe acute respiratory distress syndrome (ARDS) in the most severe cases. Patient concerns: Metastatic cancer has historically been a contraindication for the use of extracorporeal life support (including extracorporeal membrane oxygenation or extracorporeal membrane oxygenation [ECMO]). With advancing technology and medicine, this contraindication has been called into question. Prior case reports describe the use of ECMO in complicated cases of metastatic cancer and even choriocarcinoma with lung metastasis and refractory ARDS. Diagnoses: We describe a case in which a patient with choriocarcinoma in viable pregnancy developed lung metastasis and ARDS. Interventions: The patient was managed with venovenous ECMO successfully. Outcomes: The patient was cannulated for VV-ECMO for 14 days with subsequent full pulmonary recovery. Lessons: The purpose of this work is to help providers understand the broad utility of ECMO and the need to assess candidacy for this therapy on a case by case basis, even in the setting of metastatic cancer.

Acute induction of psoriasis-like skin inflammation disturbes vascular tone and provokes a rapid blood pressure response in mice

Abstract Background Psoriasis is the most common chronic skin disease worldwide. Furthermore, it is an independent cardiovascular risk factor. Several genetic and inducible murine models reproduce specific aspects of the human disease. In mice genetically overexpressing IL-17A in keratinocytes or dendritic cells, we coulod show both aspects of the disease: cutaneous hallmarks and the vascular phenotype. The most popular inducible model consists of topical application of Imiquimod (IMQ), a Toll-like receptor 7/8 agonist. In this model, cardiovascular aspects have not been studied yet. Therefore, we examined vascular and hemodynamic effects in this most popular murine psoriasis model. Methods C57BL/6J mice were treated with 5% IMQ or sham cream. During treatment, we measured bodyweight, skin thickness and skin water loss. After 10 days, aortic relaxation studies were performed. For assessment of vascular inflammation, inflammatory cell infiltration into the aortic tissue was investigated by flow cytometric analysis. To record physical activity, blood pressure and heart rate, carotid catheters were implanted two weeks before treatment with IMQ. Blood pressure and heart rate were continuously recorded by receiver platforms. Results IMQ treatment resulted in severe skin inflammation and induced a skin barrier defect resulting in a 7-fold increase of transcutaneous water loss (from 11±6 ml/m2h to 77±30 ml/m2h). Physical activity decreased more than 50% after d1 of treatment and normalized at d7. Telemetric recording revealed a reflex tachycardia at 1d of IMQ-application (from 492±21 bpm to 524±20 bpm) followed by a significant reduction of heart rate for the next two days (456±18bpm). Systolic blood pressure showed a similar trend: after a fast increase (from 120±13 mmHg to 127±18 mmHg), blood pressure dropped below baseline at d2/3 with a subsequent recovery. We could display a highly significant positive correlation between blood pressure and heart rate during the treatment (R=0.6; p≤0.0001). Aortas from animals after 10d of IMQ-treatment showed an increased infiltration of CD45+ and CD11b+ inflammatory cells but no change of responsiveness to endothelium dependent and independent vasodilators in organ chamber studies. Conclusion Skin treatment with IMQ had severe implications on the hemodynamic system: After an initial peak of heart rate and blood pressure, mice showed significantly lower values for two days with a subsequent full recovery. Moreover, bodyweight and physical activity were significantly altered during treatment. Our data indicate that skin inflammation and inflammatory skin barrier disruption by IMQ forces a compensatory whole-body response. 10 days of IMQ-treatment resulted in vascular inflammation without mediating vascular dysfunction. In summary, we could reveal that IMQ-induced psoriasis, as the most popular murine psoriasis model worldwide, has extensive effects on the cardiovascular system. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Boehringer Ingelheim Foundation “Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications”German Federal Ministry for Education and Research (BMBF EDU-V24)

Fully reversible spectral compression of arbitrary pulsed data signals

Data signals consisting of arbitrarily modulated sequences of pulses are extensively used for processing and communication applications. The spectral extent of such signals is determined by the bandwidth of the individual pulses in the sequence, which imposes a fundamental limit to the maximum amount of information that can be transmitted or processed per time period. In this work, we propose and experimentally demonstrate that the frequency spectrum occupied by a data-modulated pulse sequence can be significantly compressed to well below the individual pulse bandwidth while still maintaining the temporal duration of the pulses in the sequence and without losing any of the information carried by the signal. The proposed method involves fully reversible linear transformations of the data signal along the time and frequency domains. We demonstrate successful pulse-shape-preserving spectral compression and subsequent full waveform and information recovery of a ∼ 10 Gb / s optical pulse sequence, modulated by an arbitrary data pattern, liberating over 60% of its bandwidth. These findings should prove useful for applications in signal processing, communications, and others.

The role of pyridostigmine in recovery from motor paralysis in a snakebite patient with an allergic reaction to anti-snake venom

A 30-year-old woman presented as an emergency with a history of snakebite 5 h previously with signs of bulbar palsy, ptosis, respiratory distress and weakness of all four limbs. Mechanical ventilation, anti-snake venom (ASV) and supportive management were immediately instituted. With the third dose of ASV, an early anaphylactic reaction ensued. Subsequent management with corticosteroids and antihistamines over the next few days allowed consciousness to return but muscle power did not improve beyond 2/5. A trial of intravenous neostigmine with glycopyrrolate, however, improved motor power in all four limbs to 3/5. Oral pyridostigmine at 60 mg every 8 h allowed subsequent full motor recovery in all four extremities. We suggest consideration of pyridostigmine to promote motor recovery after an allergic reaction to ASV.

Multifocal Tuberculosis with Prolonged Paradoxical Reaction

This is a case report describing successful treatment of a challenging case of an 18-year old previously healthy high school male student with multifocal tuberculosis involving the spleen and mediastinal and abdominal lymph nodes confirmed by histopathology of splenectomy tissue. The patient initially responded well to antituberculosis therapy with complete resolution of fever and improvement in his general health and weight. However, two months after initiation of anti-tuberculosis therapy, the patient developed paradoxical reaction manifest as recurrence of fever that persisted for five months and was associated with enlargement of lymph nodes. The fever failed to abate with continuation of the same antituberculosis therapy. Despite reassurance that the fever was due to a prolonged paradoxical reaction, a decision was made by the family to seek advice in another hospital where lymphoma was excluded again by histopathological examination of an excisional lymph node biopsy that revealed caseating granulomatous lymphadenitis and negative tuberculosis stain, culture, and polymerase chain reaction. The patient was continued on anti-tuberculosis therapy and treated with corticosteroids that resulted in complete resolution of fever and subsequent full recovery from his tuberculosis.

Pharmacological Modulation of Sleep Homeostasis in Rat: Novel Effects of an mGluR2/3 Antagonist.

Increasing vigilance without incurring the negative consequences of extended wakefulness such as daytime sleepiness and cognitive impairment is a major challenge in treating many sleep disorders. The present work compares two closely related mGluR2/3 antagonists LY3020371 and LY341495 with two well-known wake-promoting compounds caffeine and d-amphetamine. Sleep homeostasis properties were explored in male Wistar rats by manipulating levels of wakefulness via (1) physiological sleep restriction (SR), (2) pharmacological action, or (3) a combination of these. A two-phase nonlinear mixed-effects model combining a quadratic and exponential function at an empirically estimated join point allowed the quantification of wake-promoting properties and any subsequent sleep rebound. A simple response latency task (SRLT) following SR assessed functional capacity of sleep-restricted animals treated with our test compounds. Caffeine and d-amphetamine increased wakefulness with a subsequent full recovery of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and were unable to fully reverse SR-induced impairments in SRLT. In contrast, LY3020371 increased wakefulness with no subsequent elevation of NREM sleep, delta power, delta energy, or sleep bout length and count, yet REM sleep recovered above baseline levels. Prior sleep pressure obtained using an SR protocol had no impact on the wake-promoting effect of LY3020371 and NREM sleep rebound remained blocked. Furthermore, LY341495 increased functional capacity across SRLT measures following SR. These results establish the critical role of glutamate in sleep homeostasis and support the existence of independent mechanisms for NREM and REM sleep homeostasis.

P99 Neonatal subdural haematoma following forceps-assisted delivery: a systematic review of the literature

ObjectivesSubdural haematoma (SDH) is a recognised complication of forceps-assisted delivery (FAD). There are no guidelines regarding its management. This study aims to provide a better insight into the management and outcomes of neonatal SDH post FAD.DesignRetrospective review of our neonatal database and systematic review of the literature.SubjectsNeonatal cases presented with SDH after FAD.MethodsRetrospective database search of cases managed in our unit between January 20 111 and January 2018. Systematic review of the literature was performed using PRISMA guidelines. Inclusion criteria: (i) neonates, (ii) forceps-assisted delivery, (iii) evidence of SDH on imaging, with or without other traumatic lesions.ResultsA literature search yielded 9 studies with 30 patients meeting our inclusion criteria, In addition three cases were identified from our institutional database. 42% (n=14) had their SDH managed surgically, with subsequent full neurological recovery in 57%. In comparison, 95% (n=18) of the conservatively managed patients made a full recovery. Hydrocephalus was present in 1 and 11 of the conservatively managed and surgically managed patients, respectively.ConclusionsConservative management can lead to a full neurological recovery in SDH following FAD in neonates. However, a significant number may still need neurosurgical intervention for the SDH or subsequent hydrocephalus, therefore we advocate early transfer to a specialist neuroscience centre.

X-Ray Reverberation Mapping and Dramatic Variability of Seyfert 1 Galaxy 1H 1934-063

A fraction of active galactic nuclei (AGN) exhibit dramatic variability, which is observed on timescales down to minutes in the X-ray band. We introduce the case study of 1H 1934-063 (z = 0.0102), a Narrow-line Seyfert 1 (NLS1) among the brightest and most variable AGN ever observed with XMM-Newton. This work includes spectral and temporal analyses of a concurrent XMM-Newton and NuSTAR 2015 observation lasting 130 kiloseconds, during which the X-ray source exhibited a steep (factor of 6) plummet and subsequent full recovery of flux level, accompanied by deviation from a single log-normal flux distribution. We rule out Compton-thin obscuration as the cause for this dramatic variability observed even at NuSTAR energies. In order to constrain coronal geometry, dynamics, and emission/absorption processes, we compare detailed spectral fitting with Fourier-based timing analysis. Similar to other well-studied, highly variable Seyfert 1s, this AGN is X-ray bright and displays strong reflection features. We find a narrower broad iron line component compared to most Seyfert 1s, and constrain black hole spin to be < 0.1, one of the lowest yet discovered for such systems. Combined spectral and timing results are consistent with a dramatic change in the continuum on timescales as short as a few kiloseconds dictating the nature of this variability. We also discover a Fe-K time lag, measuring a delay of 20 seconds between relativistically-blurred reflection off the inner accretion flow and the hard X-ray continuum emission.

Pheochromocytoma – when acute medicine comes to the surgeon's rescue and vice versa. Case report of a patient presenting unmanageable haemodynamic instability during elective surgery for pheochromocytoma

We report and discuss the case of a 51-year-old patient undergoing elective laparoscopic surgery for pheochromocytoma after 10 days of medical pre-treatment. After anaesthetic induction, a deep level of anaesthesia could not prevent the onset of repeated hypertensive peaks, followed by severe hypotensive periods. Once the surgical incision was made, the patient developed acute pulmonary oedema along with significant oxygen desaturation. The decision was made to stop the surgery and transfer the patient to the intensive care unit (ICU) for further support and management. Unfortunately, additional monitoring and symptomatic treatment did not help haemodynamic stabilisation. In the absence of any external stimulation or medical support, the oscillation of blood pressure (BP) continued with peaks every 20 minutes up to 300 mmHg systolic blood pressure (SBP) and falls down to 30 mmHg SBP. The patient also sustained two episodes of cardiac arrest from which he recovered. Facing this unmanageable situation, a decision was made after a multi-disciplinary discussion to go back to surgery in order to remove the source of adrenergic stimulation. Surgery by laparotomy was performed and catecholamine substitution was provided. Nevertheless, after tumour removal, BP dropped leading to a third cardiac arrest that was successfully managed. Following a 10-day stay in the ICU, the patient left with subsequent cardiac stabilisation and full recovery.

Contralateral Optic Neuritis Following Silicone Oil Endotamponade for Retinal Detachment

Silicone oils are used for ocular endotamponade to treat complicated retinal detachments. Neurological complications of silicone oil endotamponade are uncommon. Case reports have documented optic nerve atrophy and migration of the silicone oil into the subarachnoid space and ventricular system. However, optic neuritis contralateral to the treated eye has not been previously described. We report a 60 year-old-woman who underwent repair of retinal detachment with silicone oil in the left eye and later developed optic neuritis in the right eye. Immediately after the introduction of the silicone oil, the patient complained of severe pain in the left orbit with radiation into the left temporal and occipital areas. Subsequently, she developed vision loss in the previously unaffected right eye. She received a high dose intravenous steroids for three days with subsequent full recovery of vision in the right eye. Two weeks later, she had a second episode of decreased vision in the right eye, however this time, the vision in her right eye did not improve. MR imaging shows inflammation on the optic nerves and silicone oil in the ventricular system. Conclusions: Silicone oil can migrate into the nervous system and may provoke optic neuritis in the contralateral eye.

Ventricular Assist Device in Single-Ventricle Heart Disease and a Superior Cavopulmonary Anastomosis.

Our objective is to describe the use of a ventricular assist device (VAD) in single-ventricle patients with circulatory failure following superior cavopulmonary anastomosis (SCPA). We performed a retrospective chart review of all single-ventricle patients supported with a VAD following SCPA. Implantation techniques, physiologic parameters while supported, medical and surgical interventions postimplant, and outcomes were reviewed. Four patients were supported with an EXCOR Pediatric (Berlin Heart Inc., The Woodlands, TX, USA) following SCPA for a median duration of 10.5 days (range 9-312 days). Selective excision of trabeculae and chords facilitated apical cannulation in all patients without inflow obstruction. There were two pump exchanges in the one patient supported for 312 days. Two patients were evaluated by cardiac catheterization while supported. Three of four patients were successfully bridged to transplantation. One patient died while supported. All patients had significant bleeding at the time of transplantation, and one required posttransplant extracorporeal membrane oxygenation with subsequent full recovery. VAD support can provide a successful bridge to transplantation in patients with single-ventricle circulation following SCPA. A thorough understanding of the challenges encountered during this support is necessary for successful outcomes.

TrkB-Mediated Protection against Circadian Sensitivity to Noise Trauma in the Murine Cochlea

Noise-induced hearing loss (NIHL) is a debilitating sensory impairment affecting 10%-15% of the population, caused primarily through damage to the sensory hair cells or to the auditory neurons. Once lost, these never regenerate [1], and no effective drugs are available [2, 3]. Emerging evidence points toward an important contribution of synaptic ribbons in the long-term coupling of the inner hair cell and afferent neuron synapse to maintain hearing [4]. Here we show in nocturnal mice that night noise overexposure triggers permanent hearing loss, whereas mice overexposed during the day recover to normal auditory thresholds. In view of this time-dependent sensitivity, we identified a self-sustained circadian rhythm in the isolated cochlea, as evidenced by circadian expression of clock genes and ample PERIOD2::LUCIFERASE oscillations, originating mainly from the primary auditory neurons and hair cells. The transcripts of the otoprotecting brain-derived neurotrophic factor (BDNF) showed higher levels in response to day noise versus night noise, suggesting that BDNF-mediated signaling regulates noise sensitivity throughout the day. Administration of a selective BDNF receptor, tropomyosin-related kinase type B (TrkB), in the night protected the inner hair cell's synaptic ribbons and subsequent full recovery of hearing thresholds after night noise overexposure. The TrkB agonist shifted the phase and boosted the amplitude of circadian rhythms in the isolated cochlea. These findings highlight the coupling of circadian rhythmicity and the TrkB receptor for the successful prevention and treatment of NIHL.

Penile lesion with inguinal adenopathy after intravesical Bacillus Calmette-Guerin instillation therapy

Intravesical Bacillus Calmette-Guérin (BCG) is widely used as an adjuvant therapy in the treatment of non-muscle-invasive bladder cancer. BCG is generally well tolerated, though localized and systemic infectious complications may occur. Infection of the glans and inguinal adenopathy are rare local complications of intravesical BCG therapy. Traumatic urethral catheterization is one of the main causes. We report the case of a 75-year-old male who developed granulomatous balanitis and enlarged inguinal lymph nodes after five cycles of intravesical BCG treatment for transitional cell carcinoma of the bladder. Histology revealed giant cell granuloma. Oral antituberculous treatment was initiated with subsequent full recovery of penile lesions and adenopathy. Physicians who administer BCG must be familiar with the possible complications and their adequate management and should inform patients about the side-effects accordingly.

Renoprevention: A New Concept for Reengineering Nephrology Care—An Economic Impact and Patient Outcome Analysis of Two Hypothetical Patient Management Paradigms in the CCU

Background: The impact of acute kidney injury (AKI) on chronic kidney disease (CKD) progression remains uncertain; the common belief is that AKI in CKD is short-lived with subsequent full recovery. However 25.2% of end-stage renal disease (ESRD) Medicare patients all experienced antecedent AKI. We recently described a new syndrome of ESRD following AKI, the syndrome of rapid-onset end-stage renal disease (SORO-ESRD). Renoprevention, which we described in 2009, is the application of preventative measures to reduce AKI incidence. Methods: This is a descriptive study based on real clinical experience. Two hypothetical 69-year-old Caucasian male patients, A and B, with symptomatic coronary artery disease (CAD) presented for elective cardiac catheterization and subsequent coronary artery bypass graft procedures; renoprevention was applied in patient A but not in B. Results: Aggressive fluid repletion, withholding Lisinopril 40 mg once daily (QD) 1 week before hospitalization (hydralazine substituted) in A—earlier discharge after 6 days, transient minimal change in serum creatinine. Patient B continued on Lisinopril 40 mg QD, experienced prolonged hypotension needing pressors—severe oliguric AKI, volume overload, daily RRT for 6 days, recovered kidney function, was discharged after 20 days. Hospital charges were $68,580 (A) versus $154,650 (B). If patient B had developed ESRD (SORO-ESRD), the savings would be humongous. Conclusion: A more forceful and pragmatic application of renoprevention strategies in the coronary care unit (CCU)—preemptive withholding of nephrotoxics including renin angiotensin aldosterone system (RAAS) blockers, aggressive prevention of perioperative hypotension, avoiding nephrotoxic exposure as contrast, and antibiotics–leads to less AKI, potentially less SORO-ESRD, better patient outcomes, and massive dollar savings. Such paradigm shifts would constitute major rethinking in current nephrology practice, a form of nephrology practice reengineering.

Rituximab is highly effective for pure red cell aplasia and post-transplant lymphoproliferative disorder after unrelated hematopoietic stem cell transplantation

Pure red cell aplasia (PRCA) and post-transplant lymphoproliferative disorder (PTLD) constitute rare complications after allogeneic hematopoietic stem cell transplantation (AlloHSCT). The incidence of EBV-PTLD is above 1%, but it may increase in patients with well-known risk factors such as EBV seronegativity at the time of transplantation, T-cell depletion of donor grafts, HLA mismatch and use of antithymocyte globulin (ATG) for prophylaxis of graft versus host disease. The risk factors for PRCA were defined and they include: 1) elevated post-transplant anti-donor isohemagglutinin titers, 2) reduced-intensity conditioning before transplant, 3) the presence of anti-A agglutinin and 4) ciclosporin for graft versus host disease (GVHD) prophylaxis and 5) transplant from sibling donor. The anti-CD20 monoclonal antibody rituximab remains the first line treatment for PTLD following AlloHSCT, but its efficacy in PRCA is limited. Reduction of immunosuppression is also strongly advised. This is the first report on an adult patient who simultaneously developed PRCA and PTLD after ABO-mismatched AlloHSCT. The early introduction of rituximab resulted in prompt resolution of clinical symptoms with subsequent full recovery.

Laser corneal biofilm disruption for infectious crystalline keratopathy

Crystalline keratopathy can be successfully treated by the Nd:YAG laser. We present two cases of crystalline keratopathy managed this way. A 36-year-old female contact lens wearer presented with crystalline keratopathy following recent treatment with topical steroids and antibiotics for a corneal abscess. In this case crystalline keratopathy developed despite the intensive topical antibiotic treatment. A 55-year-old man with a history of acne rosacea, chronic myelomonocytic leukaemia, asthma and Crohn's disease presented with crystalline keratopathy following an episode of infectious keratitis. Treatment with the Nd:YAG laser to the area of involvement was instituted in both cases. Noticeable resolution occurred within days, with subsequent full recovery. No side-effects from the use of the Nd:YAG laser were noted. There have been only two cases previously reported using this treatment modality.

Neonatal echocardiographic assessment in preterm infants born from twin to twin transfusion syndrome treated by fetoscopic laser coagulation: Comparison with dichorionic twins

UENPS.371 From a dustbin to NICU: Successful treatment of profound neonatal hypothermia Patricia Konopova⁎, Jan Janota, Jana Termerova, Iva Burianova, Hana Martanova, Magdalena Paulova, Jiri Zach Thomayer University Hospital, Prague Background and aim Severe neonatal hypothermia is defined as a core body temperature below 28 °C. The development of hypothermia can be predisposed by numerous factors including hypoglycaemia, drugs, and environmental exposure. At present, there is no agreement regarding the best therapeutic approach [1]. We report the treatment of profound hypothermia in a newborn with subsequent full recovery. Materials and methods Term male newborn was found uncovered in a dustbin, with umbilical cord attached to placenta. He was exposed to environmental temperature of −3 °C for approximately 30 min. The core temperature on admission was 25 °C. He was spontaneously breathing, had hypotension, bradycardia, and poor peripheral perfusion. Vigorous treatment was commenced, including non-aggressive, slow re-warming at 0.5–1.0 °C per hour using external warming modalities, oxygen, volume expanders, heparinization, and antibiotic treatment. Results During first 24 h rectal temperature raised from 25 °C to 37 °C, heart rate from 60 to 140/minute (Fig. 1). No adverse effects were observed during, and after re-warming. The following tests were performed during the hospitalisation and were normal: neurological examination, cranial ultrasound, EEG, hearing, and ophthalmology screen. At the time of discharge (day 21), the newborn had no significant neurological abnormalities. Fig. 1. Rectal temperature and heart rate within first 24 hours. Conclusions A slow re-warming procedure can be successfully used when treating a profoundly hypothermic newborn.

Phase II Study of Gemcitabine and Cisplatin in Patients with Previously Untreated Extensive Stage Small Cell Lung Cancer: Southwest Oncology Group Study 9718

This phase II study (S9718) evaluated the antineoplastic activity and tolerability of the combination of gemcitabine and cisplatin in previously untreated patients with extensive stage small cell lung cancer (ES-SCLC). Chemonaive patients with ES-SCLC, received gemcitabine 1250 mg/m intravenously (IV) over 30 minutes on days 1 and 8 and cisplatin 75 mg/m IV over 30 to 60 minutes on day 1. Treatments were repeated every 21 days for a maximum of six cycles. A total of 88 patients were enrolled in the study; seven patients were not eligible and one did not receive treatment; 80 patients were fully assessable for survival, response, and toxicity. Objective response was observed in 42 patients (53%; 95% confidence interval [CI]: 41%-64%) with two patients (3%; 95% CI: 0%-8%) achieving a complete response. Median PFS was 5 months (CI, 4.2-5.9 months), and median overall survival was 8.8 months (95% CI: 7.8-9.5 months). The 1- and 2-year survival rates were 27.5% (95% CI: 17.7%-37.3%) and 4% (95% CI: 0%-8%), respectively. The most common toxicity was neutropenia. Grade 3 and 4 neutropenia was noted in 17 (21%) and 17 (21%) patients, respectively. Two patients developed febrile neutropenia, with subsequent full recovery. Twenty-one patients (23%) developed grade 3 thrombocytopenia. Grade 4 thrombocytopenia was seen in only one patient. The most common nonhematologic toxicities included grade 3 and 4 vomiting in 12 (21%) patients and fatigue in nine (10%) patients. Two patients (3%) died of respiratory infections while on treatment. The combination of gemcitabine and cisplatin is an active and reasonably well tolerated regimen for the treatment of ES-SCLC. It does not appear to offer any compelling advantages over other commonly used two drug regimens in this disease.

Coronary Collaterals in Full Effect

A 59-year-old man with no relevant medical history was referred to our clinic for analysis of exertional chest pain. He had noticed slowly progressive symptoms approximately 6 months before referral, although they did not prohibit his daily 12-mile cycling exercise routine. During diagnostic 99m-technetium-sestamibi single photon emission computed tomography treadmill stress testing, the ECG showed pathological ST-segment depression, and the patient had anginal chest pain. Three-dimensional reconstructed scintigraphic perfusion images (Figure 1) displayed a substantial reversible defect in the anterolateral myocardium with only a mild resting perfusion defect in the distal segment of the anterior wall, which coincided with a small area of subendocardial fibrosis visualized …