Palliative care as a Fundamental Human Right: where are we at in Italy?

Abstract: The right to live with dignity during the final stages of existence, enshrined in national and supranational Charters of Rights, represents a significant step towards humanizing medicine and is integral to the right to health. Palliative Care, rooted in health, dignity, and therapeutic self-determination, has emerged as a fundamental human right and a moral imperative within health systems. It seeks to alleviate suffering, emphasizing the holistic well-being of patients with life-limiting illnes-ses. This paper provides an analysis of the current situation of Palliative Care in Italy and examines its critical aspects, also in relation to the issues found in other European and non-European countries. In Italy, although laws have been enacted to ensure the provision of Palliative Care, its availability remains inconsistent across different regions. Financial constraints and insufficient support hinder the comprehensive dissemination of these services. Recognizing the significance of Palliative Care, the Catholic Church also endorses its implementation as a response to human suffering and an approach to end-of-life care. Efforts to strengthen Palliative Care are critical to meeting the rising demand and ensuring access to compassionate and dignified care for all individuals in need. Through legislative advancements and adequate resources, Italy can make significant strides in advancing the provision of Palliative Care.

Gender Gap in academic medicine: a narrative review and the Italian forensic context.

Background: Gender gap is a neologism that identifies the disparity between social and professional conditions experienced by females compared to males. The disparity increases as one ascends the academic hierarchy. In recent years, the debate has expanded, and more options have been planned for the elimination of the current gender gap. Methods: This research was conducted by examining the landscape of the gender gap, particularly in the academic forensic medicine field. Our analysis involved reviewing papers published between 2006 and 2024, identified through electronic database searches (PubMed). The search terms used were: "gender gap" AND "academic" AND "medicine" AND "leadership." In total, we analyzed 85 papers. Additionally, we examined data from forensic medicine residency programs. Conclusions: The representation of women in medicine is well-known. Despite the increasing number of women in leadership positions in medicine, they still lag significantly behind men. These data highlight a situation that could be seen as grounds for an accusation of "academic abuse". In the Italian forensic residency programs, less than 20% are led by women, and among these, not all hold the rank of full professor. Although a certain rebalancing is already underway, the gap is still significant. There are already regulations obliging local authorities to promote gender equality in councils, companies, and institutions under their jurisdiction. It would be desirable to consider minimum quotas for female participation in university competitions. This would be a first step toward eliminating the gender gap in academic and forensic medical fields.

Loss of chance: the uncertainty of the event or the uncertainty of the conduct? Case Series and Medicolegal Considerations.

Background: The concept of damages for loss of chance originated in France in 1877 and was adapted to healthcare in 1962. In Italy, it was first introduced in healthcare liability in 2004, with Civil Court of Cassation decision No. 4400. Italian jurisprudence recognizes the loss of chance as an independent, legally and economically assessable damage, distinct from the actual outcome lost. The landmark St. Martin Judgments of 2019 further established that such damages can be claimed if they involve appreciable, serious, and consistent values. This requires proving a causal link between the conduct and the lost chance, based on established civil law criteria. Case report: 1) a 71-year-old man whose lung carcinoma was not diagnosed in time, leading to a significant reduction in survival chances. 2) a woman whose breast cancer diagnosis was delayed, resulting in a more advanced stage and decreased survival prospects. Discussion: In medical professional liability, the Supreme Court requires a high probability or certainty of causation for recognizing the causal link between wrongful conduct and damage. The assessment involves proving both the causal link and the reasonable probability of a lost opportunity's realization. Hypothetical damage is insufficient for compensation. Conclusions: The compensability of loss of chance relies on proving the causal link between the negligent act and the uncertain event, where the impact on the patient's non-pecuniary sphere is significant. Medicolegal practice faces challenges in distinguishing between causality and damage, which can lead to confusion between biological damage and damage from loss of opportunity.

Artificial intelligence and future perspectives in Forensic Medicine: a systematic review.

Objective: Artificial intelligence (AI) is the ability of a computer machine to display human capabilities such as reasoning, learning, planning, and creativity. Such processing technology receives the data (already prepared or collected), processes them, using models and algorithms, and answers questions about forecasting and decision-making. AI systems are also able to adapt their behavior by analyzing the effects of previous actions and working then autonomously. Artificial intelligence is already present in our lives, even if it often goes unnoticed (shopping networked, home automation, vehicles). Even in the medical field, artificial intelligence can be used to analyze large amounts of medical data and discover matches and patterns to improve diagnosis and prevention. In forensic medicine, the applications of AI are numerous and are becoming more and more valuable. Method: A systematic review was conducted, selecting the articles in one of the most widely used electronic databases (PubMed). The research was conducted using the keywords "AI forensic" and "machine learning forensic". The research process included about 2000 Articles published from 1990 to the present. Results: We have focused on the most common fields of use and have been then 6 macro-topics were identified and analyzed. Specifically, articles were analyzed concerning the application of AI in forensic pathology (main area), toxicology, radiology, Personal identification, forensic anthropology, and forensic psychiatry. Conclusion: The aim of the study is to evaluate the current applications of AI in forensic medicine for each field of use, trying to grasp future and more usable applications and underline their limitations.

First Case of Medically Assisted Suicide in Italy Set New Legal Perspectives.

Abstract: The first act of assisted suicide in Italy was recently carried out. This event is an absolute novelty for the country, affected by recent legislative changes aimed only at introducing the right to interrupt health treatments and, therefore, carry out exclusively omissive end-of-life acts. These normative provisions lay their foundations in a cultural context centered on the protection of the right to life and health; however, the cases that have occurred over time, including the famous story of DJ Fabo, have led the Constitutional Court to re-evaluate these dictates, introducing in 2019 the right to resort to assisted suicide procedures within well-defined areas, including incurability of the condition, the serious suffering of the individual and the retained ability to stand trial. The case addressed concerns a quadriplegic subject who was the victim of a road accident. Following consultation with a specialized institution, the subject made the decision to undergo an assisted sui-cide procedure in Italy. Having obtained the authorization from the competent authorities, he started a fundraiser to finance the devices and drugs required and, finally, he died. The opening by Italy towards the assisted suicide procedure represents a great step towards a broad context, as well as a decisive act for the purpose of protecting the right to self-determination of the individual. However, the current legislative framework presents significant criticalities and shortcomings. In first place, the dissonance between the laws in force and the judicial sentences is likely to generate problems of uneven application of the rules in a country dominated by the principle of Civil Law. Furthermore, the need for the applicant to fully self-finance the procedure clearly clashes with the constitutional principle of free access to care. Then emerges the need for a guideline document regarding the completion of the procedure itself, the times, methods and drugs implied, in order to significantly reduce the decision-making process by the ethics committees that still weighs on each individual case. Finally, conside-ring what has been observed on the subject of voluntary termination of pregnancy, it is necessary to ask what will be the general orientation of the doctors called to perform the act and whether they will be given the opportunity to express their refusal. The case analyzed could represent the beginning of a new era for Italian culture, but the large-scale application of assisted suicide procedures requires the introduction of legislative provisions that definitively eliminate the critical issues that have emerged so far.

COVID-19 Risk Management: a Survey among Italian physicians.

Abstract: The COVID-19 pandemic had a significant global impact on public health. The increasing demand for intensive care and the closure of several health facilities has led to a reduction in the assistance of non-COVID patients. In our study, we investigated what changes health professionals have experienced in their professional activities and how they coped with them. A questionnaire was sent to 146 doctors, focused on three subjects: type of activity carried out during the pandemic; use of personal protective equipment (PPE) and recourse to vaccination; current medical liability profiles related to COVID-19. The questionnaire was completed by 111 doctors. The study showed no significant differences in the questionnaire response as regards the demographic and work variables of the participants (gender, age, area of specialties). Most of doctors assisted potentially positive patients, which also imposed derogations on their safety. Most of the complaints were about the low adequacy of PPE provision and about the compromission of specialist medical care. The interest in safety among participants was revealed by the high compliance to vaccination, with almost complete coverage. The questionnaires showed that most doctors (72,7%) believe that specialist medical care has been impaired during the COVID-19 pandemic. Secondly, a high percentage of participants (79.8%) expressed the need for both civil and criminal limitation of liability in connection with work in the management of SARS-Cov-2 patients. In conclusion, this survey tried to contribute to the identification of the main problems presented by healthcare professionals. Their versatility was a crucial element for the management of the pandemic, but also highlighted the need for health institutions to prepare pandemic plans in the future, with adequate and constant updating. Concerns were raised regarding financial deficits and legal protection. Political decisions must be entrusted to enhance medical assistance and to avoid the increasing phenomenon of defensive medicine.

Rules on informed consent and advance directives at the end-of-life: the new Italian law.

End-of-life decisions are an emergent issue for bioethical debates and practical concerns among health professionals. On December 2017, Italy enacted a new law named "Rules about informed consent and advance directives", which promotes the relationship of care in a fiduciary sense through the implementation of a correct and exhaustive information. It is also prescribed to record in writing all the patients' decisions about consent or refusal. Furthermore, the law explicitly forbids unreasonable therapeutic obstinacy for terminal patient, legitimizing deep palliative sedation. Finally, the law establishes the use of "advance directives" as a written document by which adults and capable people can express their wishes regarding health treatments and diagnostic tests in anticipation of a possible future incapacity. The law provides that doctors must comply with these directives, unless they appear clearly incongruous or not corresponding to the patient's current clinical condition.

A rare case of Spinal Epidural Abscess following mesotherapy: a challenging diagnosis and the importance of clinical risk management. Considerations concerning uncommon risk factor for development of Spinal Epidural Abscess and its prevention.

Spinal Epidural Abscess (SEA) is a rare pyogenic infection localized between dura mater and vertebral periostium. The development of SEA is associated with the presence of medical co-morbidities and risk factors that facilitate bacterial dissemination. It is possible distinguish two type of SEA: primary SEA due to pathogen hematogenous dissemination and secondary SEA resulting from direct inoculation of pathogen. This entity, very uncommon, shows a prevalence peak between the 5th and the 7th decade of life with predominance in males. The case is a 44 years old Caucasian man with chronic low back pain, treated with physiotherapy and anti-inflammatory drugs. Following an episode of acute severe exacerbation of pain, the patient underwent four session of dorsal and lumbo-sacral area mesotherapy. One month after the last session, the patient experienced acute sever lumbar pain, radiated to left lower limb and accompanied by fever and vomiting. During hospitalization, elevated levels of white blood cells and C Reactive Protein (CRP) were found. Moreover, a vertebral magnetic resonance imaging revealed the presence of intramedullary lesion. Furthermore, methicillin sensitive staphylococcus aureus was isolated from three blood cultures and antibiotic therapy was performed. In our case the patient had the typical SEA onset, without any specific risk factors excepting the execution of four session of mesotherapy. Aim of this study is to explain risk factors for the SEA development and to clarify how act as preventive measure, because also acupuncture can promote bacterial infection.

Response to letter to the Editor regarding physical restraint in psychiatric setting.

The following letter addresses the issues of the applicability of physical restriction, with particular attention to the therapeutic regime and its meaning as a therapeutic or restrictive provision, while considering possible alternative measures in the context of Italian jurisprudence. The letter, in response to the questions posed by Cioffi and Tomassini, examines the possible legal implications for doctors and suggests that the integration of jurisprudence and psychiatry seems to be mandatory to define the operational protocols for the management of physical restraint. La seguente lettera affronta il problema relativo all'applicabilità della contenzione fisica, con particolare riferimento al regime terapeutico, nonché la sua valenza giuridica quale misura terapeutica o restrittiva, considerando eventuali approcci alternativi. La lettera, in risposta alle domande poste da Cioffi e Tomassini, esamina le possibili implicazioni legali cui possono incorrere i medici nell'applicare la contenzione fisica, suggerendo la necessità di un'integrazione tra le norme giurisprudenziale e la scienza psichiatrica, al fine di definire i protocolli operativi di gestione della contenzione fisica.

The importance of Post Mortem Computed Tomography (PMCT) in the reconstruction of the bullet trajectory.

INTRODUCTION: Post Mortem Computed Tomography (PMCT) and 3D reconstruction provide a powerful tool in the evaluation of the causes of death, distinguishing between those findings related to traumas and those related to post mortal changes. It has proven to be extremely useful in case of violent deaths as a support to the traditional autopsy. AIM OF THE STUDY: The aim of the study is to prove the essential role of PMCT in the determination of the cause of death. For this purpose, we present a case of homicide where CT scans were performed before the autopsy, thus bringing to the resolution of an otherwise controversial death. CASE PRESENTATION: A 17 years old male died from a gunshot fired by a policeman during a chase. There were some controversies in this case that brought it to the national mediatic attention. PMCT reconstructed images showed the entry point and the ballistic trajectory of the bullet, moreover, PMCT high sensitivity in the evaluation of bone lesions, made the technique diriment in the clarification of the sequence of events that brought to the death of the subject, resolving the controversies of the case. In fact, it showed that the trajectory of the bullet could have not been compatible with the victim's family thesis.

Is it time for international guidelines on physical restraint in psychiatric patients?

The freedom-restraining measures used during Involuntary Health Treatment (IHT) are highly criticized in the medical community. Physical restraint techniques are currently largely used worldwide in Psychiatry. The use of restraints against the patient's will can be considered a serious intrusion of basic human rights and even an act of violence against the patient. In all cases, the restraint should not lead to injuries or damage to the patient's health and should be implemented with a respect of the human rights and dignity. Generally, the use of restraint should be considered as a last resource, when all the other methods have failed. Since it represents the principal freedom-limitation measure, it should be constantly monitored by physicians who apply these methods. The case of a 58 years-old white male, affected by chronic schizoaffective disorder and cannabinoid dependence, was under involuntary medical treatment as a consequence of antisocial behavior. During the IHT he suffered firstly a pharmacological restraint and then a physical restraint in order to suppress a slight state of agitation. The patient was completely blocked to the bed for more than 80 hours and died after three days of hospitalization. The aim of this study is to evaluate the suitability of restrictive methods for psychiatric patients in order to establish specific rules to prevent abuse of restraint techniques and even to help physicians to treat psychiatric patients.

Stem Cell Leukemia: how a TALented actor can go awry on the hematopoietic stage.

TAL1/SCL/TCL5 is a critical transcription factor for hematopoietic stem cell maintenance and regulation of early hematopoiesis. However, aberrant expression of TAL1 in committed T-cell precursors is also directly implicated in the development of T-cell leukemia. Roughly 25 years ago TAL1 was identified in early hematopoietic cells and involved in leukemia. Here, we review the wealth of knowledge gained since then on its physiological roles and mechanisms by which TAL1 ectopic expression contributes to leukemogenesis. We emphasize recent findings that shed light into the intricacies of TAL1 (epi)genetic regulation and the transcription network orchestrated by this major T-cell oncogene. Importantly, an exciting time is coming when data using the mechanistic knowledge accumulated on TAL1 may be used to develop novel anti-leukemia targeted therapies.

KIT-D816V oncogenic activity is controlled by the juxtamembrane docking site Y568-Y570.

Mutation of KIT receptor tyrosine kinase at residue D816 results in ligand-independent constitutive kinase activity. This mutation occurs in most patients with mastocytosis, a myeloproliferative neoplasm, and is detected at lower frequencies in acute myeloid leukemia and in germ cell tumors. Other KIT mutations occur in gastrointestinal stromal tumors (GIST) and mucosal melanoma. KIT is considered as a bona fide therapeutic target as c-kit mutations are driving oncogenes in these pathologies. However, several evidences suggest that KIT-D816V mutant is not as aggressive as other KIT mutants. Here, we show that an intracellular docking site in the juxtamembrane region of KIT maintains a negative regulation on KIT-D816V transforming potential. Sixteen signaling proteins were shown to interact with this motif. We further demonstrate that mutation of this site results in signaling modifications, altered gene expression profile and increased transforming activity of KIT-D816V mutant. This result was unexpected as mutations of the homologous sites on wild-type (WT) KIT, or on the related oncogenic FLT3-ITD receptor, impair their function. Our results support the hypothesis that, KIT-D816V mutation is a mild oncogenic event that is sufficient to confer partial transforming properties, but requires additional mutations to acquire its full transforming potential.

Chronic intermittent intravenous insulin therapy: a new frontier in diabetes therapy.

The limited success achieved in controlling diabetes and its complications with conventional insulin therapy suggests the need for reevaluation of the appropriateness of insulin administration protocols. Indeed, conventional subcutaneous insulin administration produces slowly changing blood insulin levels and suboptimal hepatocyte insulinization resulting in impaired hepatic capacity for processing incoming dietary glucose. The novel approach to insulin administration known as chronic intermittent intravenous insulin therapy (CIIIT) delivers insulin in a pulsatile fashion and achieves physiological insulin concentration in the portal vein. Done as a weekly outpatient procedure combined with daily intensive subcutaneous insulin therapy, this procedure has been shown to (1) significantly improve glycemic control while decreasing the incidence of hypoglycemic events, (2) improve hypertension control, (3) slow the progression of overt diabetic nephropathy, and (4) reverse some manifestations of diabetic autonomic neuropathy (e.g., abnormal circadian blood pressure pattern, severe postural hypotension, and hypoglycemia unawareness).

Prevalence of osteoporosis in women: variation with skeletal site of measurement of bone mineral density.

OBJECTIVE: To determine retrospectively the prevalence of osteoporosis in a referral population of female patients and to compare the sensitivity for diagnosing osteoporosis by dual-energy x-ray absorptiometry (DXA) measurements of bone mineral density (BMD) at multiple skeletal sites. METHODS: We studied the data from 625 consecutive women (mean age, 57.3 +/- 13.9 years), who had been referred to our center for lumbar spine (anteroposterior [AP] and lateral region) and hip (femoral neck [FN], Ward's triangle [WT], trochanter, intertrochanteric region, and total hip) BMD measurements with use of DXA (Hologic QDR-2000) between June 1994 and July 1998. RESULTS: Osteoporosis (based on the World Health Organization definition--T-score of -2.5 or lower for BMD) was diagnosed by DXA at the following sites: AP spine in 21.7%, lateral spine in 43.2%, FN in 33.6%, WT in 49.1%, trochanter in 26.1%, intertrochanteric region in 25.9%, and total hip in 28.4% of study patients. Significant site differences were found in the prevalence of osteoporosis between the lateral and AP spine (P < 0.001), as well as between WT and the FN, trochanter, intertrochanteric region, and total hip (P < 0.001). In a subgroup of 71 women, forearm (ultradistal radius and radius 1/3 region) BMD results indicated low sensitivity for diagnosing osteoporosis, similar to that seen at the AP spine, trochanter, and intertrochanteric region. Not surprisingly, the prevalence of osteoporosis increased with advancing age (15.5% in patients younger than 50 years, in comparison with 59.6% in those older than 69 years of age). The frequency of misclassification of patients (osteoporosis at one site and normal BMD at another) with use of the seven measurement sites was 16.6% (104 of the 625 patients). CONCLUSIONS: For diagnosis of osteoporosis, DXA BMD measurements are significantly more sensitive at the lateral spine than at the AP spine, as well as at WT than at the FN, trochanter, intertrochanteric region, and total hip sites.

Effect of intensive insulin therapy on progression of overt nephropathy in patients with type 1 diabetes mellitus.

OBJECTIVE: To assess the effects of chronic (long-term) intermittent intravenous insulin therapy (CIIIT) on the progression of overt nephropathy in patients with type 1 diabetes mellitus. METHODS: We undertook a retrospective longitudinal three-center study of 31 patients with type 1 diabetes mellitus and overt nephropathy, who were receiving intensive subcutaneous insulin therapy (four insulin injections daily) and weekly CIIIT. All study patients had follow-up consultations weekly for at least 12 months (mean duration, 37.0 +/- 4.6 months). Each patient had monthly hemoglobin A(1c) (by high-performance liquid chromatography) and semiannual creatinine clearance determinations. RESULTS: The hemoglobin A(1c) levels declined significantly from 8.6 +/- 0.6% to 7.6 +/- 0.3% (P = 0.0062) during the study period. The creatinine clearance remained essentially unchanged (from 46.1 +/- 3.0 mL/min per 1.73 m 2 at baseline to 46.0 +/- 3.9 mL/min per 1.73 m 2 at the end of the observation period, with an average annualized slope increase of 3.39 +/- 1.5 mL/min per year--no significant difference). CONCLUSION: The addition of CIIIT to intensive subcutaneous insulin therapy in patients with type 1 diabetes mellitus seems to arrest or appreciably reduce the progression of overt diabetic nephropathy, as well as substantially improve their glycemic control.

Effect of intensive insulin therapy on abnormal circadian blood pressure pattern in patients with type I diabetes mellitus.

OBJECTIVE: To assess the effect of tight glycemic control on the abnormal circadian BP pattern associated with IDDM. DESIGN: Retrospective, randomized control trial. SETTING: Diabetes Research Institute, ambulatory. PATIENTS: Seventy-four IDDM patients (22M/52F) on intensive subcutaneous insulin therapy (ISIT) were selected for this study. INTERVENTIONS: Group A patients (11M/25F) underwent, in addition to ISIT, weekly chronic intermittent intravenous insulin therapy (CIIIT) (TT Aoki et al, Lancet, 1993, 432:515-8). Group B patients (11M/27F) were continued on ISIT alone. All study patients were followed for 3 months on this regimen. They were seen weekly by the investigators and underwent monthly HbA1c determinations and 24-h ambulatory BP monitoring. RESULTS: Glycemic control improved significantly in group A subjects (HbA1c decreased from 7.9% to 7.2%, p = 0.0002) but changed little in the group B subjects (p = NS). The night/day systolic BP ratio decreased from 0.97 to 0.94 (-3.10%) in group A and increased from 0.95 to 0.98 (+3.16%) in group B subjects (p = 0.224). The night/day diastolic ratio decreased from 0.93 to 0.90 (-3.23%) in group A and increased from 0.91 to 0.94 (+3.29%) in group B subjects (p = 0.0037). CONCLUSIONS: CIIIT performed in IDDM patients on ISIT further improves their glycemic control and tends to reverse or at least prevent further deterioration of their abnormal circadian BP pattern.

Effect of chronic intermittent intravenous insulin therapy on antihypertensive medication requirements in IDDM subjects with hypertension and nephropathy.

OBJECTIVE: The prevalence of systemic hypertension is increased in patients with diabetes. In this prospective, randomized, crossover clinical trial, we assessed antihypertensive effects of chronic intermittent intravenous insulin therapy (CIIIT) on insulin-dependent diabetes mellitus (IDDM) subjects with hypertension and nephropathy by monitoring the amount of antihypertensive medication (AHM) required to maintain blood pressure (BP) < or = 140/90 mmHg. RESEARCH DESIGN AND METHODS: After a stabilization period, 26 hypertensive IDDM subjects were randomly assigned to a control or treatment phase for 3 months and then crossed over into the opposite phase for another 3 months. Addition of CIIIT during the treatment phase was the only procedural difference between the control and treatment phases. RESULTS: The AHM dosage requirements for maintenance of the baseline BP levels decreased significantly (46%; P < 0.0001) and linearly over time (P < 0.0058) during the treatment phase, while remaining essentially unchanged during the control phase. CONCLUSIONS: Our data suggest that CIIIT markedly improves BP control, as evidenced by the significantly reduced AHM dosage requirements in subjects with IDDM and hypertension, possibly through an improvement in vascular reactivity.

Long-term intermittent intravenous insulin therapy and type 1 diabetes mellitus.

An important defect in insulin-dependent diabetes mellitus (IDDM) is that the liver does not meet its full fuel-processing function, because many of the enzymes involved depend on high insulin concentrations in the portal vein. We tried to reactivate the liver by long-term treatment of IDDM patients with intravenous insulin in pulses, with the aim of achieving high portal-vein concentrations during and after a glucose meal. We studied 20 IDDM patients with brittle disease; despite use of a four-injection regimen with manipulation of insulin doses, diet, and physical activity, and frequent clinic visits for at least a year, these patients still had wide swings in blood glucose and frequent hypoglycaemic reactions. The intermittent therapy consisted of 7-10 pulses of intravenous insulin, infused while the patient was ingesting carbohydrate, primarily glucose, during the first hour of a 3 h treatment; three treatments were given in a day. After 2 consecutive days' treatment, patients were treated for 1 day per week. No patient was withdrawn from the study. At the time of this analysis the duration of intermittent treatment ranged from 7 to 71 months (mean 41 [SE 5] months). Haemoglobin A1C concentrations declined from 8.5 (0.4)% at the end of the stabilisation phase to 7.0 (0.2)% at the analysis point (p = 0.0003). During the same time the frequencies of major and minor hypoglycaemic events also fell significantly (major 3.0 [1.1] to 0.1 [0], minor 13.0 [2.6] to 2.4 [0.8] per month; both p < 0.0001). Because the use of saline rather than insulin pulses would have led to unacceptable hyperglycaemia we opted for a historical control design. The absence of a true control group limits the interpretation of these preliminary results, but we believe further studies of hepatic and muscle metabolism before and after long-term intermittent intravenous insulin therapy would be worth while.