Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis.

BACKGROUND: The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive. METHODS: A comprehensive literature search was conducted to identify relevant studies published up to the study's cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI). RESULTS: The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies' findings. Further research is needed to clarify these associations. CONCLUSION: The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition's origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.

Increased picture-word interference in chronic and recreational users of cocaine.

OBJECTIVE: The correct production of speech depends on the effective use of inhibitory control. Cocaine abuse has been linked to impaired inhibition in the verbal and nonverbal domains. The aim of this study was to evaluate the possible impairment of the inhibitory control process engaged in the production of language among chronic cocaine users, both in rehabilitation and recreational contexts. METHOD: Researchers obtained an index of semantic interference from a picture-word task performed by chronic cocaine users in rehabilitation (Experiment 1) and recreational cocaine polydrug users (Experiment 2). Cocaine users in both groups were matched for age and intelligence with cocaine-free health controls. Performance on the picture-word task was analyzed by repeated-measures analyses of variance. RESULTS: Both groups of cocaine users showed significantly more semantic interference than their respective cocaine-free control group. These results suggest a deficit in the ability to inhibit interfering information. CONCLUSIONS: The present findings suggest that cocaine use, even at recreational levels, is associated with specific impairments in the inhibitory mechanism that reduces the activation of overt competing responses in language production. This impairment results in the inefficient avoidance of irrelevant information, inducing errors and slower responses during the production of spoken language.

Diffuse myocardial calcification in a drug addict, complicating advanced life support.

Myocardial calcification is a rare echocardiographic finding, which is often found in patients who have suffered from a myocardial infarction. Rarely, myocardial calcification may be present in individuals without a significant medical history. Until today, there has not been a published case report emphasising the relation between myocardial calcification and cocaine usage. Herein, we report a case of a young male with diffuse calcification of the left ventricular myocardium, who had an addiction to cocaine. This case highlights an uncommon etiology for myocardial calcification and it may lead to further studies about cardiotoxic effects of cocaine.

The unique psychostimulant profile of (±)-modafinil: investigation of behavioral and neurochemical effects in mice.

Blockade of dopamine (DA) reuptake via the dopamine transporter (DAT) is a primary mechanism identified as underlying the therapeutic actions of (±)-modafinil (modafinil) and its R-enantiomer, armodafinil. Herein, we explored the neurochemical and behavioral actions of modafinil to better characterize its psychostimulant profile. Swiss-Webster mice were implanted with microdialysis probes in the nucleus accumbens shell (NAS) or core (NAC) to evaluate changes in DA levels related to acute reinforcing actions of drugs of abuse. Additionally, subjective effects were studied in mice trained to discriminate 10 mg/kg cocaine (i.p.) from saline. Modafinil (17-300 mg/kg, i.p.) significantly increased NAS and NAC DA levels that at the highest doses reached ~300% at 1 h, and lasted > 6 h in duration. These elevated DA levels did not show statistically significant regional differences between the NAS and NAC. Modafinil produced cocaine-like subjective effects at 56-100 mg/kg when administered at 5 and 60 min before the start of the session, and enhanced cocaine effects when the two were administered in combination. Despite sharing subjective effects with cocaine, modafinil's psychostimulant profile was unique compared to that of cocaine and like compounds. Modafinil had lower potency and efficacy than cocaine in stimulating NAS DA. In addition, the cocaine-like subjective effects of modafinil were obtained at lower doses and earlier onset times than expected based on its dopaminergic effects. These studies suggest that although inhibition of DA reuptake may be a primary mechanism underlying modafinil's therapeutic actions, non DA-dependent actions may be playing a role in its psychostimulant profile.

Asymptomatic Cocaine Abuse　- Myocardial Tissue Characterization Using Cardiac Biomarkers and Cardiovascular Magnetic Resonance Imaging.

BACKGROUND: Use of cocaine is widespread and associated with several cardiovascular diseases. Recent CMR studies indicate frequent myocardial scar/fibrosis in asymptomatic cocaine abusers (CA).Methods and Results:This study used a combination of advanced CMR tissue characterization techniques, including late gadolinium enhancement (LGE) for focal, and extracellular volume (ECV) imaging for diffuse myocardial injury/fibrosis, with circulating biomarkers for a comprehensive characterization of myocardial injury. We included 20 cardiac asymptomatic CA and a control group of 20 healthy volunteers. The comprehensive assessment included physical examination, resting ECG, exercise ECG, cardiac biomarkers, transthoracic echocardiogram and CMR. We did not find significant differences between CA and controls either in functional CMR parameters such as LVEDVi, LVESVi, LVEF, LV mass index, or in global myocardial ECV. Neither CA nor controls had evidence of myocardial edema on T2-weighted CMR, but 8 CA (40%), and none of the controls had focal myocardial scar (P<0.01). Interestingly, CA with focal myocardial scar on LGE had significantly higher high-sensitivity troponin I (hs-TNI) compared with CA without focal scar (median, 1.7 ng/L; IQR, 1.3-2.5 ng/L vs. 0.6 ng/L; 0.4-1.3 ng/L; P<0.01). CONCLUSIONS: Focal myocardial injury in terms of subtle LGE in 40% of asymptomatic CA was associated with higher hs-TNI. Comprehensive assessment including advanced ECV imaging indicates a focal rather than diffuse pattern of myocardial involvement in asymptomatic CA.

[A cause of palatal necrosis not to ignore]. / Une cause de nécrose palatine à ne pas méconnaître.

We report a case of pseudotumoral nasal septum and hard palate perforation in a 42-years-old man. The diagnosis retained after differential diagnosis exclusion was necrotic midfacial lesion due to chronic inhalation of cocaine. This condition can mimic vasculitis, primary tumors and granulomatous infections. Differential diagnosis and pathophysiology of this condition will be discussed in this anatomo-clinical case.

Bilateral self-inflicted infectious dacryoadenitis.

The aim of this report is to present a case of a patient with bilateral lacrimal gland abscesses in the course of dacryoadenitis. A 45-year-old female patient with a long history of cocaine abuse presented with bilateral bacterial dacryoadenitis and upper lid inflammation with purulent discharge from a palpebral wound of the right upper lid. The diagnosis was confirmed with microbiology culture and an orbital CT scan, which revealed lacrimal gland abscesses. The patient admitted to vigorous eye scratching, which we believe was the mechanism responsible for the process. The infection resolved on targeted antibiotic therapy. This is the first reported case of bilateral infectious dacryoadenitis produced in a self-inflicted mechanism in a cocaine addict.

In vitro and in vivo stability of a highly efficient long-acting cocaine hydrolase.

It is recognized as a promising therapeutic strategy for cocaine use disorder to develop an efficient enzyme which can rapidly convert cocaine to physiologically inactive metabolites. We have designed and discovered a series of highly efficient cocaine hydrolases, including CocH5-Fc(M6) which is the currently known as the most efficient cocaine hydrolase with both the highest catalytic activity against (-)-cocaine and the longest biological half-life in rats. In the present study, we characterized the time courses of protein appearance, pH, structural integrity, and catalytic activity against cocaine in vitro and in vivo of a CocH5-Fc(M6) bulk drug substance produced in a bioreactor for its in vitro and in vivo stability after long-time storage under various temperatures (- 80, - 20, 4, 25, or 37 °C). Specifically, all the tested properties of the CocH5-Fc(M6) protein did not significantly change after the protein was stored at any of four temperatures including - 80, - 20, 4, and 25 °C for ~ 18 months. In comparison, at 37 °C, the protein was less stable, with a half-life of ~ 82 days for cocaine hydrolysis activity. Additionally, the in vivo studies further confirmed the linear elimination PK profile of CocH5-Fc(M6) with an elimination half-life of ~ 9 days. All the in vitro and in vivo data on the efficacy and stability of CocH5-Fc(M6) have consistently demonstrated that CocH5-Fc(M6) has the desired in vitro and in vivo stability as a promising therapeutic candidate for treatment of cocaine use disorder.

Cocaine-Induced Acute Extremity Compartment Syndrome: A Rare Case Report.

There is a dearth of research connecting acute extremities compartment syndrome to cocaine. Here, we present a case of a forty-year-old guy who is actively using cocaine and comes to the emergency room with excruciating right leg pain and swelling. Physical examination revealed substantial tachycardia, lack of dorsalis pedis pulses, stiff and painful calf muscles, and absence of plantar reflexes in the right lower extremities after sleeping on his right leg. A positive urine drug screen for cocaine, severe rhabdomyolysis, and acute renal damage warranted further laboratory testing. A diagnosis of compartment syndrome was established based on the lack of dorsalis pedis pulses in the right lower extremity and radiographic evidence of oedematous alterations in the calf muscles with perimuscular edema. For this case, acute renal injury was done, and treatment with fluid, hemodialysis, and right lower extremity double-compartment fasciotomies have been used. After that, his clinical situation improved, and no other dialysis sessions were required. Cocaine usage has been linked to rhabdomyolysis; nevertheless, compartment syndrome is an extremely uncommon consequence, particularly in the absence of severe damage or extended immobility.

Endovascular Management of Acute Lower Limb Ischemia Linked to Cocaine Abuse: A Case Report.

Cocaine abuse is a public health concern with well-documented cardiovascular complications. However, acute limb ischemia remains a rare and underreported consequence. We present a case of a 36-year-old man with acute right lower limb ischemia following heavy cocaine use, successfully managed with systemic heparin and intra-arterial nitroglycerin. The case highlights considering cocaine as a potential cause of acute limb ischemia and the efficacy of endovascular therapy. Further case reports with this diagnosis and their management are crucial for establishing the best strategies and improving outcomes in these scenarios.

ANCA-associated vasculitis presenting with isolated neurological manifestations in a patient with cocaine abuse: a case report and literature review.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare conditions predominantly affecting small vessels of skin, musculoskeletal, pulmonary, renal, and rarely central and peripheral nervous systems. Isolated neurological manifestations of AAV are uncommon and challenging to diagnose. Cocaine has been reported as a potential trigger for the development of AAV. There are only a few case reports of isolated neurological involvement in cocaine-induced AAV with poorly characterized histopathological features. We present a unique case of AAV with isolated neurological manifestations presenting with multiple cranial neuropathies, leptomeningeal enhancement on imaging and histopathologic evidence of small-vessel vasculitis in the leptomeninges and brain and extensive dural fibrosis in a patient with cocaine abuse. The patient's progressive neurological deficits were controlled after starting immunosuppression with rituximab and prednisone. We also reviewed the literature to provide the diagnostic overview of AAV and evaluate intervention options. To our knowledge, this is the first case of AAV with isolated neurological manifestations and histopathologic evidence of small-vessel vasculitis in a patient with cocaine abuse. Patients with multiple cranial neuropathies and meningeal involvement should be screened for AAV, especially if they have a history of cocaine abuse.

Left Ventricular Non-compaction and Associated Cardiomyopathy Presenting With Cardiac Failure: A Case Report.

The characteristic structural anomaly of the heart in the left ventricular non-compaction (LVNC) is identified with a prominent layer of the trabecular meshwork, thin compacted myocardium, and intertrabecular recesses within the depths of the left ventricle. Despite growing clinical recognition, the prevalence of LVNC in adults and the full clinical spectrum remain poorly explored. The disease shows heterogeneous phenotypes from an asymptomatic presentation to severe cardiac complications like cardiac failure, arrhythmias, and thromboembolic events. Current diagnostic practices for LVNC lack standardized guidelines, making patient management difficult. We here report a case of an adult patient who presented with features of congestive cardiac failure and on detailed imaging with echocardiogram and magnetic resonance imaging (MRI) was diagnosed to have LVNC. We here also emphasize that there is a great need for refined diagnostic criteria that include genetic, clinical, and imaging data. Cases of LVNC with full-blown phenotypic expression should be used for diagnostic criteria.

Prelamination of the Forearm Flap for Soft Palate Reconstruction: A Case Report.

Microsurgical reconstruction is nowadays the treatment of choice of several head and neck deformities that otherwise could be repaired with limited or unsatisfactory results. The forearm free flap has its own goals expecially the possibility to reconstruct small and extremely specialized anatomical structures such as the soft palate. The abuse of drugs like cocaine, generally taken by sniffing, can produce vascular impairment in nasal and oral tissues producing, as long as the abuse is kept, necrosis of facial anatomical structures and increase of the empty space in the depth of the face or nose. The consequences are generally represented by palatal fistulas or defect, leak of food or drink from the nose, and rhinolalia. Prelamination of the flap before microvascular transfer ensures not only preparation ofadequate tissue volume to resurface the defect but also optimization of the venous outflow. This two times approach, consisting first in preparation and then elevation/transfer of the flap, gives the chances to ensure viability of the flap itself and organize the surgical strategy several times to reduce forthcoming complications. The authors believe that this technical modification could be used for many other chronic defects in the head and neck region but could also be extended, with experience, to bigger defects. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03870-7.

Substance Use Disorders (SUDs) and Risk of Cardiovascular Disease (CVD) and Cerebrovascular Disease (CeVD): Analysis of the Nationwide Inpatient Sample (NIS) Database.

BACKGROUND:  Substance use continues to be on the rise in the United States and has been linked to new onset cardiovascular diseases (CVDs) and cerebrovascular disorders (CeVDs). We aimed to study the association between the types of substance use disorders (SUDs) with specific subtypes of CVDs and CeVDs among hospitalized patients using the National Inpatient Sample (NIS) Database. METHODS:  A retrospective study of the NIS database (2016-2017) using the ICD-10-CM codes was performed. The hospitalizations with a secondary diagnosis of SUDs were identified. Weighted univariate analysis using the Chi-square test and multivariate survey logistic regression analysis was performed to evaluate for the incidence, prevalence, and odds of association between vascular events and SUDs. RESULTS:  There were a total of 58,259,589 hospitalizations, out of which 21.42% had SUDs. SUDs were more common in the younger age group of 18-50, males, and the lower median household income group. We found a significant association of acute ischemic stroke (AIS) with amphetamine dependence (adjusted odds ratio, aOR 1.23, 95% confidence interval, CI 1.14-1.33), cocaine-related disorders (1.17, 1.12-1.23), and nicotine dependence (1.42, 1.40-1.43). There was a significant association between intracerebral hemorrhage with amphetamine dependence (2.58, 2.26-2.93), cocaine-related disorders (1.62, 1.46-1.79), and alcohol-related disorders (1.35, 1.01-1.82). The association of subarachnoid hemorrhage (SAH) was noted to be higher with amphetamine dependence (1.82, 1.48-2.24) and nicotine dependence (1.47, 1.39-1.55). The patients with nicotine dependence had greater odds of having a myocardial infarction (1.85, 1.83-1.87), those with cocaine-related disorders had higher odds of having angina pectoris (2.21, 1.86-2.62), and patients with alcohol-related disorders had higher odds of developing atrial fibrillation (1.14, 1.11-1.17) in comparison to non-SUDs. CONCLUSION:  Our study demonstrates the variability of CVD and CeVD in patients hospitalized for SUD. Findings from our study may help promote increased awareness and early management of these events. Further studies are needed to evaluate the specific effects of frequency and dose on the incidence and prevalence of CVD and CeVD in patients with SUD.

Sleep Disorder and Cocaine Abuse Impact Purine and Pyrimidine Nucleotide Metabolic Signatures.

Disturbances in the circadian rhythm alter the normal sleep-wake cycle, which increases vulnerability to drug abuse. Drug abuse can disrupt several homeostatic processes regulated by the circadian rhythm and influence addiction paradigms, including cravings for cocaine. The relationship between circadian rhythm and cocaine abuse is complex and bidirectional, and disruption impacts both brain function and metabolic profiles. Therefore, elucidating the impact of circadian rhythm changes and cocaine abuse on the human metabolome may provide new insights into identifying potential biomarkers. We examine the effect of cocaine administration with and without circadian rhythm sleep disruption (CRSD) on metabolite levels and compare these to healthy controls in an in vivo study. A metabolomics analysis is performed on the control, CRSD, cocaine, and CRSD with cocaine groups. Plasma metabolite concentrations are analyzed using a liquid chromatography electrochemical array platform. We identify 242 known metabolites compared to the control; 26 in the CRSD with cocaine group, 4 in the CRSD group, and 22 in the cocaine group are significantly differentially expressed. Intriguingly, in the CRSD with cocaine treatment group, the expression levels of uridine monophosphate (p < 0.008), adenosine 5'-diphosphate (p < 0.044), and inosine (p < 0.019) are significantly altered compared with those in the cocaine group. In summary, alterations in purine and pyrimidine metabolism provide clues regarding changes in the energy profile and metabolic pathways associated with chronic exposure to cocaine and CRSD.

Psychomotor Symptoms in Chronic Cocaine Users: An Interpretative Model.

According to the latest estimates, there are around 24.6 million cocaine users worldwide, and it is estimated that around a quarter of the population worldwide has used cocaine at some point in their lifetime. It follows that such widespread consumption represents a major risk for public health. Long-term use of cocaine, in addition to being related to many cerebral and cardiovascular diseases, is increasingly associated with a higher incidence of psychomotor symptoms and neurodegenerative disorders. In recent years, numerous studies have shown an increased risk of antipsychotic-induced extrapyramidal symptoms (EPSs) in patients with psychotic spectrum disorders comorbid with psychostimulant misuse, particularly of cocaine. In the present paper, we describe the case of a young patient on his first entry into a psychiatric setting with previous cocaine misuse who rapidly presented psychomotor symptoms and was poorly responsive to symptomatic therapy consisting of benzodiazepines and anticholinergics, in relation to the introduction of various antipsychotics (first, second, and third generation). Furthermore, we propose neurobiological mechanisms underlying the hypothesized increased vulnerability to psychomotor symptoms in chronic cocaine abusers. Specifically, we supposed that the chronic administration of cocaine produces important neurobiological changes, causing a complex dysregulation of various neurotransmitter systems, mainly affecting subcortical structures and the dopaminergic and glutamatergic pathways. We believe that a better understanding of these neurochemical and neurobiological processes could have useful clinical and therapeutic implications by providing important indications to increase the risk-benefit ratio in pharmacological choice in patients with psychotic spectrum disorders comorbid with a substance use disorder.

Sub-lethal toxicity and elimination of the cocaine metabolite, benzoylecgonine: a narrative review.

Cocaine abuse is a serious global public health and social problem, and cocaine detoxification remains a challenge. Benzoylecgonine (BE) is the main toxic metabolite after cocaine consumption, with a longer retention time in the body and environment than cocaine itself. According to many studies, the toxicity of BE to humans is as significant as cocaine itself. Moreover, BE is recognized as an addictive drug contaminant in the environment, especially the freshwater system, leading to worries of its ecotoxicity. Extensive studies on the adverse effects of BE on both humans and ecology have been conducted, showing a marked sub-lethal toxicity of BE to diverse organisms. To eliminate BE in vivo and in vitro, various elimination methods have been developed and their BE removal capacity were evaluated. In this review, we aimed to summarize information in the literature to understand better BE toxicity and elimination that may facilitate the clinical treatment of cocaine abuse. By studying the critical role of BE in cocaine abuse, we propose that the ideal treatment for cocaine abuse should not only detoxify cocaine itself but also remove or degrade BE. Emphasizing the necessity of developing effective BE elimination methods is significant for the development of potential clinical treatments and environmental protections.

Foreign Body Aspiration Getting Weird: Crack Pipe Aspiration.

Inhalation of cocaine derivatives is associated with a number of pulmonary and systemic complications. We report a case of less recognized complication, the aspiration of a metallic object used as a screen for crack cocaine abuse. A 42-year-old female presented with a two-day history of gradually worsening cough and a history of "food aspiration." Her lung examination revealed wheezing and fine crackles with diminished air entry at the left base. A chest X-ray revealed an 8 mm radiopaque foreign body overlying the region of the left lower lobe bronchus, with a confirmatory computed tomography scan of the chest. An urgent bronchoscopy revealed a metallic foreign body impacted into the left lower lobe bronchus proper, soon after the takeoff of the superior segment, which was removed with forceps. The patient signed out against medical advice soon after. Though relatively uncommon, this case highlights a possible complication associated with crack cocaine abuse that may require emergent intervention.

A Genetically Modified Skin Graft for Treating Alcohol Use Disorder and/or Polysubstance Abuse With Cocaine.

Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We have developed and used a skin stem cell-based gene delivery platform and found that production of the glucagon-like peptide-1 (GLP1) from the grafted genetically modified skin reduced development and reinstatement of alcohol-induced drug-taking and seeking, voluntary oral alcohol consumption and alcohol-induced increase in dopamine (DA) levels in the nucleus accumbens (NAc). Moreover, we have developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Skin grafts-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by concurrent alcohol and cocaine injections. These results imply that gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.

Do gene expression findings from mouse models of cocaine use recapitulate human cocaine use disorder in reward circuitry?

Animal models of drug use have investigated possible mechanisms governing human substance use traits for over 100 years. Most cross-species research on drug use/addiction examines behavioral overlap, but studies assessing neuromolecular (e.g. RNA) correspondence are lacking. Our study utilized transcriptome-wide data from the hippocampus and ventral tegmental area (VTA)/midbrain from a total of 35 human males with cocaine use disorder/controls and 49 male C57BL/6J cocaine/saline administering/exposed mice. We hypothesized differential expressed genes and systems of co-expressed genes (gene networks) would show appreciable overlap across mouse cocaine self-administration and human cocaine use disorder. We found modest, but significant relationships between differentially expressed genes associated with cocaine self-administration (short access) and cocaine use disorder within reward circuitry. Differentially expressed genes underlying models of acute cocaine exposure (cocaine), context re-exposure and cocaine + context re-exposure were not consistently associated with human CUD across brain regions. Investigating systems of co-expressed genes, we found several validated gene networks with weak to moderate conservation between cocaine/saline self-administering mice and disordered cocaine users/controls. The most conserved hippocampal and VTA gene networks demonstrated substantial overlap (2029 common genes) and included both novel and previously implicated targets for cocaine use/addiction. Lastly, we conducted (expression-based) phenome-wide association studies of the nine common hub genes across conserved gene networks. Common hub genes were associated with dopamine/serotonin function, cocaine self-administration and other relevant mouse traits. Overall, our study pinpointed and characterized conserved brain-related RNA patterns across mouse cocaine self-administration and human cocaine use disorder. We offer recommendations for future research and add to the dialogue surrounding pre-clinical animal research for human disease.