Physiological Effects of Sildenafil Versus Placebo at High Altitude: A Systematic Review.

Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. High Alt Med Biol. 25:16-25, 2024. Introduction: High altitude pulmonary edema (HAPE), a life-threatening condition that affects individuals ascending to high altitude, requires the development of pulmonary hypertension. Sildenafil can be used to prevent and treat HAPE, presumably by decreasing pulmonary artery pressure (PaP). We compared the physiological effects of sildenafil versus placebo at high altitude (above 2,500 m), including the effects on PaP. Methods: We performed a systematic search of PubMed, EMBASE, and Cochrane CENTRAL for randomized controlled studies of the physiological effects of sildenafil in hypoxia in healthy individuals. We conducted a systematic review of all studies meeting our criteria. Results: Of the 14 studies that met the inclusion criteria, 8 were hypobaric hypoxia studies. Six studies reported data at rest at altitudes from 3,650 to 5,245 m. Two were simulations reporting exercise data at equivalent altitudes of 2,750-5,000 m. Nine studies used normobaric hypoxia corresponding to altitudes between 2,500 and 6,400 m. One reported only rest data, two reported rest and exercise data, and the others reported only exercise data. Sildenafil significantly reduced PaP at rest and exercise in hypobaric or normobaric hypoxia. There were no significant differences between arterial oxygen saturation (SpO2) with sildenafil in hypobaric or normobaric hypoxia at rest or exercise. There were no significant differences in heart rate or mean arterial pressure (MAP) at rest or exercise and cardiac output during exercise in hypobaric or normobaric hypoxia. Conclusions: Sildenafil significantly reduces PaP at rest and exercise in normobaric or hypobaric hypoxia. Sildenafil has no significant effects on SpO2, heart rate, cardiac output (during exercise), or MAP at rest or exercise in hypobaric or normobaric hypoxia.

Pontine and bilateral cerebellar lesion in osmotic demyelination syndrome associated with uncontrolled type II diabetes mellitus: a case report.

Osmotic demyelination syndrome (ODS) as a result of the hyperosmolar hyperglycemic state is rare and can present with variable neurological manifestation due to lysis of myelin sheath. Case presentation: A 44-year diabetic male presented with complaints of sudden onset, progressive bilateral weakness in lower limbs, and slurring of speech for the past 1.5 months. Cerebellar examination showed a bilaterally impaired finger nose test, dysdiadochokinesia, impaired heel shin test, and an impaired tandem gait. MRI brain (T2 and fluid-attenuated inversion recovery sequences) showed high signal intensity in the central pons and bilateral cerebellum. With a diagnosis of ODS with poorly controlled diabetes, he was treated with insulin, metformin, and supportive measures following which his symptoms subsided gradually. Clinical discussion: A rapid correction of hyponatremia is considered the most common cause of ODS. Variations in plasma glucose levels, a rare cause of ODS, can cause an abrupt osmolality change causing pontine and extrapontine myelinolysis. Prevention of rapid correction of hyponatremia and rapid changes in plasma osmolality in vulnerable patients is the mainstay of treatment. Conclusions: Clinical features, imaging studies, and monitoring of serum osmolality, serum glucose, and electrolytes aid in diagnosis and favorable outcomes for the patient.

Efficacy and safety of different therapies of non-steroidal anti-inflammatory drugs against antibiotic monotherapy in the treatment of uncomplicated lower urinary tract infection: A systematic review.

This systematic review aimed to evaluate the efficacy of different non-steroidal anti-inflammatory drugs therapy (monotherapy or combined with antibiotics) against antibiotics monotherapy to understand the possible role of non-steroidal anti-inflammatory drugs in managing uncomplicated urinary tract infections and reduce overall antibiotic prescription. We searched four databases: PubMed, EMBASE, Scopus, and Cochrane CENTRAL. We included randomized controlled trials, which had included non-pregnant females above 18 years, published from 2010 to 2020 AD in the English language. We assessed risk of bias (ROB) using COCHRANE ROB version 2.0. We synthesized the conclusion from low ROB studies. Among five included studies, four studies compared non-steroidal anti-inflammatory drugs monotherapy against antibiotics monotherapy, and one study compared non-steroidal anti-inflammatory drugs + antibiotic therapy against antibiotic monotherapy. All studies with low ROB showed significantly higher events of symptom resolution by day 7 with antibiotic monotherapy compared to non-steroidal anti-inflammatory drugs monotherapy. Overall, adverse events were not significantly different in two of three low risk of bias studies; however, one study reported significantly higher adverse effects with non-steroidal anti-inflammatory drugs. Non-urinary tract infection-related adverse events were more common than urinary tract infections-related adverse events in both non-steroidal anti-inflammatory drugs and antibiotic groups. Urinary tract infection-related adverse events were higher in the non-steroidal anti-inflammatory drugs group compared to antibiotics. For every 20-60 participants treated, one would develop pyelonephritis additionally in non-steroidal anti-inflammatory drugs compared to antibiotics. Antibiotics were superior to non-steroidal anti-inflammatory drugs for treating uncomplicated lower urinary tract infections. However, further studies regarding the characteristics of patients likely to develop pyelonephritis on non-steroidal anti-inflammatory drugs monotherapy, and the effectiveness and safety of a combination of non-steroidal anti-inflammatory drugs and antibiotics therapy are essential to reduce the burden of antibiotics and their associated problems.

Delayed myelopathy after organophosphate intoxication: A case report.

Organophosphate-induced delayed neuropathy, a central-distal axonopathy, passes through latent, progressive, static and improvement phases. During the improvement phase, the peripheral nerves regenerate unmasking the spinal cord lesion with myelopathic features. We report a case of a 16-year-old male who developed myelopathy 6 weeks following chlorpyrifos poisoning. He had a motor weakness of 4/5 in bilateral hips and 3/5 in bilateral knees and ankles. Spasticity and exaggerated reflexes with ankle clonus were present in the lower limbs. Sensory and the upper limb motor examinations were all normal. Pertinent blood, cerebrospinal fluid and nerve conduction tests were normal. Magnetic resonance imaging of the spine showed features of cord atrophy. Three months following physiotherapy, his power improved to 5/5 in bilateral knee and hip joints and 4/5 in bilateral ankles with spasticity. Organophosphate-induced delayed neuropathy can present as earlier as 6 weeks with myelopathy. Previous history of organophosphorous exposure is important in myelopathy or peripheral neuropathy.

A Rare and Misdiagnosed Entity Paroxysmal Nocturnal Hemoglobinuria: A Case Report.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired stem cell disorder manifesting as non-immunological hemolytic anemia, hemoglobinuria, unusual thrombosis, and renal impairment due to deficiency of glycosylphosphatidylinositol (GPI) linked proteins in red blood cells. Patients present with features of chronic non-immune intravascular hemolysis, unexplained anemia, and thrombosis at unusual sites. It is often misdiagnosed and treated as anemia due to a low degree of suspicion. In resource-limited settings, the low degree of suspicion and paucity of investigations are the major diagnostic challenges. The even bigger challenge remains in the affordability of definitive treatment after a diagnosis has been made. Herein, we present a case of PNH in a 26-year man from rural Nepal who went undetected during the initial presentation of hemolytic anemia and later presented to us with hemolytic anemia and gastrointestinal symptoms. We made the provisional diagnosis based on the clinical presentations. However, we faced challenges in reaching the final diagnosis and providing the definitive treatment due to financial constraints and limited resources. Any patient presenting with features of chronic non-immune intravascular hemolysis, unexplained anemia, and unusual thrombosis should prompt the consideration of PNH.

Virginal breast hypertrophy in a 14-year-old girl: A case report.

Reduction mammoplasty with free nipple graft can be a good choice for early pubertal patients requiring massive reduction given its low recurrence and greater patient satisfaction.